Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly. Clinical and Neurobiological Effects of Tianeptine and Paroxetine in Major Depression Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients. A controlled trial of antidepressants in patients with Parkinson disease and depression Paroxetine versus placebo: a double-blind comparison in depressed patients. Treatment of depression in patients with breast cancer: a comparison between paroxetine and amitriptyline Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin transporter promoter polymorphism Selective serotonin reuptake inhibitor treatment for generalized anxiety disorder: a double-blind, prospective comparison between paroxetine and sertraline. A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients. Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients. A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder A double-blind comparison of paroxetine, imipramine, and placebo in major depression. A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single-blind study. Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients Adjunctive sleep medications and depression outcome in the treatment of serotonin-selective reuptake inhibitor resistant depression in adolescents study. Combined Paroxetine and Clonazepam Treatment Strategies Compared to Paroxetine Monotherapy for Panic Disorder A double-blind randomized comparison of nortriptyline and paroxetine in the treatment of late-life depression: 6-week outcome. Efficacy of controlled-release paroxetine in the treatment of late-life depression. Venlafaxine XR demonstrates higher rates of sustained remission compared to fluoxetine, paroxetine or placebo Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: Outcome after long-term follow-up Clinical application of paroxetine for tapering benzodiazepine use in non-major-depressive outpatients visiting an internal medicine clinic. Tolerance and side-effects of paroxetine in elderly depressed patients. A Double‐Blind, Randomized, Fluoxetine‐Controlled, Multicenter Study of Paroxetine in the Treatment of Depression Incidence of sexual side effects in refractory depression during treatment with citalopram or paroxetine. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity Risperidone and paroxetine given singly and in combination for bipolar depression. Antidepressants Augment Natural Killer Cell Activity: In vivo and in vitro Duloxetine in the treatment of depression: A double-blind placebo-controlled comparison with paroxetine Paroxetine in the treatment of depression: a comparison with imipramine and placebo. A double-blind placebo-controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa. Genetic polymorphisms in the 5-hydroxytryptamine type 3B receptor gene and paroxetine-induced nausea. Reboxetine versus paroxetine versus placebo: effects on cognitive functioning in depressed patients Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. Pharmacogenetics of antidepressant medication intolerance. Efficacy and Tolerability of Reboxetine Compared with Citalopram: A Double-blind Study in Patients with Major Depressive Disorder A Naturalistic Long-Term Comparison Study of Selective Serotonin Reuptake Inhibitors in the Treatment of Panic Disorder Effects of the Serotonin Type 2A, 3A and 3B Receptor and the Serotonin Transporter Genes on Paroxetine and Fluvoxamine Efficacy and Adverse Drug Reactions in Depressed Japanese Patients A randomized, double‐blind, 24‐week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care Differential Antidepressant Symptom Efficacy: Placebo-Controlled Comparisons of Duloxetine and SSRIs (Fluoxetine, Paroxetine, Escitalopram) Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders Efficacy and safety of mirtazapine in major depressive disorder patients after SSRI treatment failure: an open-label trial. Serotonin transporter gene polymorphism and antidepressant response Chronic benzodiazepine use in general practice patients with depression: an evaluation of controlled treatment and taper-off: report on behalf of the Dutch Chronic Benzodiazepine Working Group. The treatment of SSRI-resistant depression in adolescents (TORDIA): in search of the best next step. Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression. The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms A comparison of paroxetine and placebo in depressed outpatients Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Selective serotonin reuptake inhibitor treatment of depression in symptomatic HIV infection and AIDS. Improvements in affective and somatic symptoms. FKBP5 polymorphisms and antidepressant response in geriatric depression Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder. The selective serotonin reuptake inhibitor paroxetine is effective in more generalized and in less generalized social anxiety disorder Effect of buspirone on sexual dysfunction in depressed patients treated with selective serotonin reuptake inhibitors. Efficacy of venlafaxine in patients with major depressive disorder who have unsustained or no response to selective serotonin reuptake inhibitors: an open-label, uncontrolled study. A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression Evidence why paroxetine dose escalation is not effective in major depressive disorder: a randomized controlled trial with assessment of serotonin transporter occupancy. Antidepressant Exposure as a Predictor of Clinical Outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) Study Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression. Paroxetine versus amitriptyline for treatment of depression associated with rheumatoid arthritis: a randomized, double blind, parallel group study. A double‐blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients Allelic Variation in the Serotonin Transporter Promoter Affects Onset of Paroxetine Treatment Response in Late-Life Depression Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression. A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer. The Alpha 2A-Adrenergic Receptor Gene Polymorphism Modifies Antidepressant Responses to Milnacipran A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. Paroxetine in major depression: a double-blind trial with imipramine and placebo. Direct Cost of Depression: Analysis of Treatment Costs of Paroxetine versus Imipramine in Canada The efficacy and safety of paroxetine compared with placebo in outpatients with major depression. A double-blind, placebo-controlled study of paroxetine in depressed outpatients. Paroxetine in the treatment of depression: a comparison with imipramine and placebo Pilot evaluation of selective serotonin reuptake inhibitor antidepressants in hot flash patients under androgen-deprivation therapy for prostate cancer Randomized Placebo-Controlled Trial of a Selective Serotonin Reuptake Inhibitor in the Treatment of Nondepressed Tinnitus Subjects Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. The safety and efficacy of paroxetine compared with placebo in a double-blind trial of depressed outpatients. Effect of paroxetine hydrochloride (Paxil®) on fatigue and depression in breast cancer patients receiving chemotherapy A Multicenter Double‐Blind Trial of Paroxetine Versus Amitriptyline in Depressed Inpatients Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out‐patients with inadequate treatment response A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial A double-blind, multicenter study in primary care comparing paroxetine and clomipramine in patients with depression and associated anxiety. Paroxetine Study Group. Bupropion sustained release versus paroxetine for the treatment of depression in the elderly. [Comparative study of paroxetine and mianserin in depression in elderly patients: efficacy, tolerance, serotonin dependence]. Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction. Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. Discontinuation Syndrome Associated with Paroxetine in Depressed Patients A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. Male Sexual Side Effects Associated with Antidepressants: A Descriptive Clinical Study of 32 Patients Cost-effectiveness and cost-utility of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine: randomised controlled trial. Influence of monoamine oxidase A and serotonin receptor 2A polymorphisms in SSRI antidepressant activity. Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical remission in a double-blind, randomized trial of amitriptyline and paroxetine. Citalopram treatment of paroxetine-intolerant depressed patients. Combination therapy with selective serotonin reuptake inhibitors and phosphodiesterase‐5 inhibitors in the treatment of premature ejaculation Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health. Remission with venlafaxine extended release or selective serotonin reuptake inhibitors in depressed patients: a randomized, open-label study. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients. Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder. A randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone. Combination of inositol and serotonin reuptake inhibitors in the treatment of depression
Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy . Physicians increasingly use selective serotonin re-uptake inhibitors ( SSRIs ) as maintenance therapy , although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants ( TCAs ) in the prevention of depression relapse and recurrence . Our objective was to evaluate , in an open trial , the efficacy of paroxetine versus nortriptyline for preventing recurrence of depression in the elderly . Elderly patients with major depression were r and omly assigned in a double-blinded fashion to receive either paroxetine or nortriptyline for the acute treatment of depression . Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent . Patients whose depression remitted continued antidepressant medication ( paroxetine n = 38 ;  nortriptyline  n = 21 ) during an open 18-month follow-up study . We examined the rates of and times to relapse and to termination of treatment for any reason . Paroxetine  ( PX ) and nortriptyline ( NT ) patients had similar rates of relapse ( 16 % vs. 10 % , respectively ) and time to relapse ( 60.3 weeks vs. 58.8 weeks , respectively ) over 18 months . A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in nortriptyline-treated patients . Paroxetine and nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period Selective serotonin reuptake inhibitors ( SSRIs ) are widely used as effective pharmacological agents to treat depressive disorders . In contrast to the SSRIs , which block the presynaptic serotonin ( 5-HT ) transporter and by this route increase the concentration of serotonin in the synaptic cleft , the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission . Both SSRIs and tianeptine are clinical ly effective ; however , their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission . To better underst and the differences between these two opposite pharmacological modes of action , we compared the changes induced by tianeptine and paroxetine on psychopathology , the hypothalamic-pituitary-adrenocortical ( HPA ) system , and cognitive functions in a double-blind , r and omized , controlled trial including 44 depressed in patients over a period of 42 days .  Depressive symptomatology significantly improved in all efficacy measures , with no significant differences between tianeptine and paroxetine . There was a trend toward better response to the SSRI among women . Assessment of the HPA system showed marked hyperactivity before the beginning of treatment , which then normalized in most of the patients , without significant differences between the two antidepressants . Cognitive assessment s showed no significant differences between the two drugs investigated . The results of the current study suggest that the initial effect , i.e. , enhancement or decrease of 5-HT release , is only indirectly responsible for antidepressant efficacy , and they support the notion that downstream adaptations within and between nerve cells are crucial . The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest Selective serotonin-reuptake inhibitors ( SSRIs ) and tricyclic antidepressants ( TCAs ) have been reported to induce extrapyramidal signs and symptoms ( EPS ) . The authors examined the change from baseline EPS , measured by an objective rating scale , in a group of elderly depressed patients participating in an ongoing r and omized , double-blind comparison of nortriptyline and paroxetine .  Mild baseline EPS were present in both groups . After 6 weeks of antidepressant treatment , patients in the nortriptyline group showed a significant decrease in total EPS scores . Patients in the paroxetine group showed a similar decrease in EPS from baseline , which did not reach statistical significance . There was no significant difference between nortriptyline and paroxetine in the change in EPS Background : Parkinson disease ( PD ) is a common neurodegenerative disease affecting up to 1 million individuals in the United States . Depression affects up to 50 % of these patients and is associated with a variety of poor outcomes for patients and their families . Despite this , there are few evidence -based data to guide clinical care . Methods : An NIH-funded , r and omized , controlled trial of paroxetine CR , nortriptyline , and placebo in 52 patients with PD and depression . The primary outcomes were the change in the Hamilton Depression Rating Scale ( HAM-D ) and the percentage of depression responders at 8 weeks . Results : Nortriptyline was superior to placebo for the change in HAM-D ( p < 0.002 ) ; paroxetine CR was not . There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks ( p < 0.079 ) . Response rates favored nortriptyline ( p = 0.024 ) : nortriptyline 53 % , paroxetine CR 11 % , placebo 24 % . In planned contrasts of response rates , nortriptyline was superior to paroxetine CR ( p = 0.034 ) . Nortriptyline was also superior to placebo in many of the secondary outcomes , including sleep , anxiety , and social functioning , while paroxetine CR was not . Both active drug treatments were well tolerated . Conclusions : Though relatively modest in size , this is the largest placebo-controlled trial done to date in patients with Parkinson disease ( PD ) and depression .  Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not . When compared directly , nortriptyline produced significantly more responders than did paroxetine CR . The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors . ARR = absolute risk reduction ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , 4th edition ; HAM-A = Hamilton Anxiety Scale ; HAM-D = Hamilton Depression Rating Scale ; MMSE = Mini-Mental State Examination ; NNT = number needed to treat ; PD = Parkinson disease ; PDQ = Parkinson ’s Disease Question naire ; PSQI = Pittsburgh Sleep Quality Index ; SCID = Structured Clinical Interview ; SSRI = selective serotonin reuptake inhibitor ; TCA = tricyclic antidepressant ; UPDRS = Unified Parkinson ’s Disease Rating Scale BACKGROUND Paroxetine is a potent and selective serotonin reuptake inhibitor ( SSRI ) . The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed out patients . METHOD A double-blind , parallel-group study was undertaken in four st and -alone centers . Patients aged 18 - 65 years , meeting DSM-III criteria for major depression , and having a Hamilton Rating Scale for Depression ( HAM-D ) score > or = 18 on the first 17 items of the HAM-D-21 were r and omized to paroxetine or placebo for 6 weeks of treatment . Efficacy outcome variables included the HAM-D , the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impressions Scale ( CGI ) , and the Covi Anxiety Scale . Tolerability was assessed by asking a non-leading question . Routine laboratory safety and vital sign data from all four centers were pooled . The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried-forward data set was employed . Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables . RESULTS Significant differences ( p < or = .05 ) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4 . Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor . Similar results were obtained when an adequate treatment group ( therapy for > or = 28 days ) was considered . A full clinical response ( CGI-severity of illness score 1 or 2 ) was seen in over 40 % of subjects . Adverse events were more common for paroxetine compared with placebo ( p < or = .01 ) . Somnolence was twice more common than nervousness . Dropout due to adverse events was similar between therapies . Paroxetine had no clinical ly significant effect on laboratory safety data or vital signs . CONCLUSION Paroxetine was an effective , well tolerated , and safe antidepressant . Side effects were typical of the SSRI class of drugs . Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects In the context of chronic physical illness , such as breast cancer , depression is associated with increased morbidity , longer periods of hospitalization , and greater overall disability . Prompt diagnosis and effective treatment is , therefore , essential . Several small studies have established the efficacy of tricyclic antidepressants ( TCAs ) in this setting , and the selective serotonin reuptake inhibitors ( SSRIs ) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile . This was a multicenter , double-blind , parallel-group study in which 179 women with breast cancer were r and omized to treatment with either the SSRI paroxetine ( 20–40mg/day ) , or the TCA , amitriptyline ( 75–150mg/day ) . After 8-weeks treatment , depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale . Clinical global impression ( CGI ) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint ; a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale . A steady improvement in quality of life was also observed in both groups . There were no clinical ly significant differences between the groups . In total , 47 ( 53.4 % ) patients in the paroxetine group and 53 ( 59.6 % ) patients in the amitriptyline group had adverse experiences , the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy . Anticholinergic effects were almost twice as frequent in the amitriptyline group ( 19.1 % ) compared with paroxetine ( 11.4 % ) . This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer BACKGROUND The effects of extended selective serotonin reuptake inhibitor ( SSRI ) treatment on weight are not well characterized . Also unknown is whether different agents have differential effects . To examine these questions , we assessed weight changes in patients r and omly assigned to long-term treatment with  fluoxetine , sertraline , or paroxetine . METHOD Patients ( N = 284 ) with major depressive disorder ( DSM-IV ) were r and omly assigned to double-blind treatment with fluoxetine ( N = 92 ) , sertraline , ( N = 96 ) , or paroxetine ( N = 96 ) for a total of 26 to 32 weeks . The mean percent change in weight was compared for each group , as was the number of patients who had > or = 7 % weight increase from baseline . RESULTS Patients ( fluoxetine , N = 44 ; sertraline , N = 48 ; paroxetine , N = 47 ) who completed the trial were included in these analyses . Paroxetine-treated patients experienced a significant weight increase , fluoxetine-treated patients had a modest but nonsignificant weight decrease , and patients treated with sertraline had a modest but nonsignificant weight increase . The number of patients whose weight increased > 7 % from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients . CONCLUSION Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used The present study aim ed to compare the effects of two currently used selective serotonin reuptake inhibitors ( SSRIs ) in Japan taking the individual background in 5-HTT gene-linked polymorphic region ( 5HTTLPR ) genotype into account . Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression . Patients with the l allele had a greater percentage reduction on the total score ( P=0.059 ) and somatic anxiety items ( P=0.026 ) of the 21-item Hamilton Depression Rating Scale ( HAM-D ) score compared to s/s genotype carriers . Paroxetine was significantly more effective than fluvoxamine in the s/s carriers , as evaluated on the percentage reduction in total score ( P=0.012 ) and core ( P=0.049 ) HAM-D after 4 weeks of medication , but not in the l/s carriers . These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs , and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) appear to be an effective class of medications for the treatment of  generalized anxiety disorder .  Within the SSRI class , however , there have been no comparative treatment studies for this disorder . Therefore , in the present study , we compared the efficacy and tolerability of 2 SSRIs , paroxetine and sertraline , in the treatment of generalized anxiety disorder . METHOD In this parallel-group , double-blind , flexible-dose study , 55 patients with primary generalized anxiety disorder ( DSM-IV criteria ) were r and omly assigned to receive either paroxetine or sertraline treatment for 8 weeks . Primary efficacy measures were the mean changes in Hamilton Rating Scale for Anxiety ( HAM-A ) scores as well as responder and remission rates based on the Clinical Global Impressions scale . Secondary efficacy measures consisted of the Indiana University Generalized Anxiety Measurement Scale and self-report ratings of anxiety , and quality -of-life outcome . Tolerability was assessed using the Systematic Assessment for Treatment Emergent Events question naire for treatment-emergent symptoms . RESULTS The intent-to-treat sample consisted of 53 patients who received medication for at least 1 week . Of the 53 patients , 43 completed the entire 8 weeks of treatment . Both paroxetine and sertraline result ed in significant decreases in mean HAM-A scores ( paroxetine = 57 % + /- 28 % ; sertraline = 56 % + /- 28 % ) . There were no differences between medication groups on response or remission rates , and tolerability was comparable . CONCLUSIONS Both paroxetine and sertraline appear similarly effective and well tolerated for the treatment of generalized anxiety disorder Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients . The authors compared the 12-week clinical outcome of older depressed patients treated with nortriptyline or paroxetine in a double-blind r and omized comparison in 116 psychiatric in patients and out patients ( mean age : 72+/-8 years ) who presented with a major depressive episode or melancholic depression .  Discontinuation and response rates were compared in patients who began or who completed treatment . The discontinuation rate due to side effects was significantly higher with nortriptyline than with paroxetine ( 33 % vs. 16 % ) . There were no significant differences between the rates of response in the Intent-to-Treat analysis ( nortriptyline : 57 % vs. paroxetine : 55 % ) , or the Completer analysis ( nortriptyline : 78 % vs. paroxetine : 84 % ) . Although paroxetine appears to be better tolerated than nortriptyline , the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients , including hospitalized patients and those with melancholic features OBJECTIVE To compare the emergent sexual effects of moclobemide and selective serotonin reuptake inhibitors ( SSRIs ) during acute and maintenance therapy in routine practice . METHOD 268 patients were evaluated for sexual function  at baseline , 6 weeks , 3 and 6 months of treatment using physician ratings and self-rating question naires . Patients received moclobemide , an reversible monoamine oxidase A inhibitor ( RIMA ) , or a SSRI ( fluoxetine , fluvoxamine , paroxetine , sertraline ) . RESULTS Baseline values were similar in all groups . Incidences of impairments of sexual functioning with treatment , whether clinical ly relevant or not , were 24.3 % with moclobemide and 61.5 % with SSRIs ( physician ratings ) , with no significant tolerance to these effects . There was a suggestion of differences between the SSRIs in their specific dysfunctions they cause . SSRIs ( 21.6 % of patients ) had about ten times the moclobemide rate ( 1.9 % ) of sexual dysfunction reported as adverse events . Antidepressant efficacy was comparable between treatments . CONCLUSION In patients for whom sexual function  is important or sexual dysfunction  is present , moclobemide should be considered a first line antidepressant BACKGROUND Fluvoxamine and paroxetine , both serotonin selective reuptake inhibitors ( SSRIs ) , were compared at two centers in a 7-week double-blind study in out patients with major depression , diagnosed by DSM-III-R criteria . METHOD Sixty patients were r and omly assigned to receive dosage titrated upward to between 50 - 150 mg/day of fluvoxamine ( N = 30 ) or 20 - 50 mg/day of paroxetine ( N = 30 ) . The mean + /- SD daily dose administered at the last assessment was 102 + /- 44 mg/day for fluvoxamine and 36 + /- 13 mg/day for paroxetine . Sixteen ( 53 % ) fluvoxamine-treated patients and 10 ( 33 % ) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug . Sample size was calculated to provide at least 85 % power at 5 % level of significance to detect at least a 1.00-point difference in mean severity of adverse events , assuming a st and ard deviation of 1.0 . RESULTS Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 + /- 7.3 ( p < .00 ) and 11.5 + /- 7.4 ( p < .00 ) , respectively , in the Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were mostly mild to moderate in severity . The most common events were headache ( N = 17 , 57 % ) , nausea ( N = 14 , 47 % ) , sweating ( N = 10 , 33 % ) , somnolence ( N = 9 , 30 % ) , diarrhea ( N = 9 , 30 % ) , dry mouth ( N = 8 , 27 % ) , dizziness ( N = 8 , 27 % ) , and , among males , impotence ( N = 3 , 21 % ) and ejaculatory abnormality ( N = 3 , 21 % ) in the paroxetine group , and headache ( N = 12 , 40 % ) , somnolence ( N = 12 , 40 % ) , nausea ( N = 11 , 37 % ) , dry mouth ( N = 11 , 37 % ) , insomnia ( N = 9 , 30 % ) , asthenia ( N = 7 , 23 % ) , and dyspepsia ( N = 7 , 23 % ) in the fluvoxamine group . The only statistically significant difference between treatment groups was for sweating ( 33 % paroxetine vs. 10 % fluvoxamine , p = .028 ) . CONCLUSION Observed differences in some side effects , although not statistically significant , indicate that when a patient has difficulty tolerating one SSRI , the clinician may choose to change to a different agent within the same class BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs The effects of treatment with serotonin ( 5-HT ) reuptake inhibitors on platelet 5-HT2 receptors , 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors ( SSRI ) , paroxetine , and fluoxetine , for the treatment of major depression . Hamilton Depression Rating Scale ( HAM-D ) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline , after 4 and 8 weeks of treatment , and were compared to 21 healthy controls . Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites , labelled with [3H]paroxetine , or 5-HT2 receptors , labelled with [3H]LSD . However , a strong correlation was observed between the HAM-D suicidality item and 5-HT2 receptor density at baseline . A marked increase in platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients compared to those with no suicidal ideation and healthy controls . Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively . These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation . Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy , particularly in suicidal depressed patients Results from a single-center , 6-week , double-blind , r and omized prospect i ve study of paroxetine , a selective serotonin reuptake inhibitor ; imipramine ; and placebo are reported . One hundred twenty out patients with a moderate-to-severe DSM-III diagnosis of major depression were r and omly assigned to one of the three treatments following a 4- to 10-day single-blind placebo washout period . Significant differences favoring paroxetine over placebo were present at endpoint on most major efficacy measures .  Paroxetine was also well tolerated ; 5 ( 15 % ) paroxetine and 5 ( 14 % ) placebo patients dropped out of the study due to adverse effects .  Imipramine , however , was comparatively poorly tolerated . Forty-five percent of  imipramine-treated patients ( N = 17 ) dropped out of the study due to adverse effects . None of the efficacy measures showed a significant difference between imipramine and placebo . This finding was probably due to the high number of imipramine patients who discontinued before they could improve . These results support the efficacy of paroxetine in the treatment of major depression and underline its favorable side effect profile compared with tricyclic antidepressants Objective : To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor ( SSRI ) and a serotonin and norepinephrine reuptake inhibitor ( SNRI ) in the treatment of depression in Parkinson disease ( PD ) . Methods : A total of 115 subjects with PD were enrolled at 20 sites . Subjects were r and omized to receive an SSRI ( paroxetine ; n = 42 ) , an SNRI ( venlafaxine extended release [ XR ] ; n = 34 ) , or placebo ( n = 39 ) . Subjects met DSM-IV criteria for a depressive disorder , or operationally defined subsyndromal depression , and scored > 12 on the first 17 items of the Hamilton Rating Scale for Depression ( HAM-D ) . Subjects were followed for 12 weeks ( 6-week dosage adjustment , 6-week maintenance ) . Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR . The primary outcome measure was change in the HAM-D score from baseline to week 12 . Results : Treatment effects ( relative to placebo ) , expressed as mean 12-week reductions in HAM-D score , were 6.2 points ( 97.5 % confidence interval [ CI ] 2.2 to 10.3 , p = 0.0007 ) in the paroxetine group and 4.2 points ( 97.5 % CI 0.1 to 8.4 , p = 0.02 ) in the venlafaxine XR group . No treatment effects were seen on motor function . Conclusions : Both paroxetine and venlafaxine XR significantly improved  depression in subjects with PD . Both medications were generally safe and well tolerated and did not worsen motor function . Classification of Evidence : This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD INTRODUCTION Although a significant amount of evidence indicates the efficacy of some antidepressants in treating psychogenic pain and somatoform disorder , very few studies have investigated their possible therapeutic action in burning mouth syndrome ( BMS ) . The purpose of this 8-week , single-blind study was to provide preliminary data on the efficacy and tolerability of amisulpride and the selective serotonin reuptake inhibitors ( SSRIs ) paroxetine and sertraline for patients with BMS . METHOD Seventy-six patients with BMS ( diagnosed according to the criteria in the literature and integrating the Diagnostic Interview Schedule-Revised for a complete psychiatric assessment ) , with no possible local or systemic causes and without concurrent major depression , were r and omly assigned to receive amisulpride ( 50 mg/day ) , paroxetine ( 20 mg/day ) , or sertraline ( 50 mg/day ) . Efficacy assessment s included a visual analogue scale ( VAS ) for pain intensity , the Hamilton Rating Scale for Depression ( HAM-D ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , and the Clinical Global Impressions scale ( CGI ) . RESULTS All 3 treatment regimens result ed in a significant improvement from baseline in burning mouth symptoms at week 8 as demonstrated by the quantitative ( mean reduction in VAS , HAM-D , and HAM-A scores ) and qualitative ( percentage of responders ) analyses . Amisulpride showed a shorter response latency than the SSRIs . No serious adverse events were reported , and the incidence of side effects did not differ among the 3 groups . None of the patients who received amisulpride withdrew from the trial , whereas withdrawal from the trial occurred within the first week of treatment in 11.5 % of patients ( N = 3 ) treated with paroxetine and in 21.7 % of patients ( N = 5 ) treated with sertraline . CONCLUSION The data suggest that amisulpride and SSRIs may be effective treatments for BMS ; they are equally effective and equally well tolerated in the short-term treatment of BMS . Amisulpride is associated with better compliance within the first week of treatment and with a shorter response latency in comparison with SSRIs . This finding may indicate that amisulpride is especially useful at the beginning of drug therapy of BMS . Double-blind , placebo-controlled trials are needed to further document the efficacy of amisulpride and SSRIs in the treatment of BMS Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor ( SSRI ) . Ninety-one hospitalised patients with a major depression ( DSM-III ) aged 65 and over from six Austrian and one German center were entered into the study , which compared the efficacy and tolerability of paroxetine versus amitriptyline . After 6 weeks both groups showed similarly good therapeutic results . In the paroxetine group , 64.3 % of the patients had a 50 % or more reduction of the HAMD total score compared to 58.1 % in the amitriptyline group . Side effects were distributed similarly in both groups . Patients in the paroxetine group showed a higher incidence of anxiety and agitation ; anticholinergic side effects were registered more often in the amitriptyline group OBJECTIVE In the Treatment of Resistant Depression in Adolescents , study participants who received medication for sleep  had a lower response rate . This report sought to clarify this finding . METHOD Depressed adolescents who had not responded to a previous adequate serotonin-selective reuptake inhibitor ( SSRI ) trial were r and omly assigned to another SSRI , venlafaxine , another SSRI+cognitive behavior therapy ( CBT ) , or venlafaxine+CBT . Augmentation with sleep medication was permitted as clinical ly indicated . RESULTS Youth who received trazodone  were six times less likely to respond than those with no sleep medication ( adjusted odds ratio [OR]=0.16 , 95 % confidence interval [ CI ] : 0.05 - 0.50 , p=0.001 ) and were three times more likely to experience self-harm ( OR=3.0 , 95 % CI : 1.1 - 7.9 , p=0.03 ) , even after adjusting for baseline differences associated with trazodone use . None ( 0/13 ) of those cotreated with trazodone and either paroxetine or fluoxetine responded . In contrast , those treated with other sleep medications had similar rates of response ( 60.0 % vs. 50.4 % , χ(2)=0.85 , p=0.36 ) and of self-harm events ( OR=0.5 , 95 % CI : 0.1 - 2.6 , p=0.53 ) as those who received no sleep medication . CONCLUSIONS These findings should be interpreted cautiously because these sleep agents were not assigned r and omly , but at clinician discretion . Nevertheless , they suggest that the use of trazodone for the management of sleep difficulties in adolescent depression should be re-evaluated and that future research on the management of sleep disturbance in adolescent depression is needed . The very low response rate of participants cotreated with trazodone and either fluoxetine or paroxetine could be due to inhibition of CYP 2D6 by these antidepressants Despite the widespread application of combined selective serotonin reuptake inhibitors ( SSRI ) and benzodiazepine treatment for panic disorder , there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy . Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment , this study is the first to address the critical question of whether continued combined treatment confers superior efficacy . This study is a r and omized , double-blind , three-arm study in patients with panic disorder ( n = 60 ) , comparing the efficacy and safety of paroxetine and placebo ( PP ) , paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase ( PC-D ) , and ongoing combination treatment ( PC-M ) . All treatment groups demonstrated significant improvement by endpoint . There was a significant advantage for the combined treatment groups early in treatment but , subsequently , outcome in all three groups was similar . A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered . The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout . Combined treatment with paroxetine and clonazepam result ed in more rapid response than with the SSRI alone , but there was no differential benefit beyond the initial few weeks of therapy . Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy BACKGROUND Some studies have suggested that selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients . The objective of this study was to compare the 6-week outcome of treatment with nortriptyline and paroxetine in older patients with a major depressive episode . METHOD A double-blind r and omized comparison of nortriptyline and paroxetine was conducted in 80 elderly ( mean + /- SD age = 75.0 + /- 7.4 years ) psychiatric in patients and out patients who presented with a major depressive episode .  Dropout and response rates were compared in patients who began or completed treatment . Rates of response of in patients and patients with melancholic depression were also compared . RESULTS Over 6 weeks , there were no significant differences in dropout rates due to side effects ( nortriptyline , 14 % vs. paroxetine , 19 % ) or for any reason ( 27 % vs. 33 % ) . Similarly , there were no significant differences between the rates of favorable response to nortriptyline or paroxetine ( intent-to-treat analysis , 57 % vs. 44 % ; completer analysis , 78 % vs. 66 % ) . Analyses restricted to in patients or to patients with melancholic depression yielded similar results . CONCLUSION Nortriptyline and paroxetine appear to have similar efficacy and tolerability in the acute ( 6-week ) treatment of older depressed patients , including hospitalized patients and those with melancholic features BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p < .002 vs. placebo ) , 65 % of paroxetine IR patients ( p = .06 vs. placebo ) , and 52 % of placebo patients . Remission , defined as a HAM-D total score < or = 7 , was achieved by 43 % of paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( < or = 2 years ) depression .  Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % for paroxetine IR , and 8.3 % for placebo . CONCLUSION Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients , including those with chronic depression The combined serotonin – norepinephrine reuptake inhibitor , venlafaxine XR , has demonstrated significant response and remission in patients diagnosed with depression when measured with the Hamilton Depression Rating Scale ( HAM-D ) . This pooled analysis of data from five studies compared the sustained remission of depressive symptoms in patients treated with venlafaxine XR , the selective serotonin reuptake inhibitors ( SSRIs ) fluoxetine or paroxetine , or placebo .  Data from 1391 subjects enrolled in five active and placebo-controlled studies who met the DSM-III-R or DSM-IV criteria for major depressive disorder were analysed . Three treatment groups were compared : venlafaxine XR ( n=560 ) , fluoxetine/paroxetine ( n=298 ) and placebo ( n=496 ) . Mean treatment duration was 8 weeks . Responders were defined as those patients whose HAM-D-21 score decreased by ≥50 % from baseline . Remission was defined as a HAM-D-17 score ≤7 . Sustained remission was defined as maintenance of remission through week 8 or the end of treatment ( if before week 8) and for ≥2 weeks . Between-group rate comparisons in outcome measures were carried out using Fisher 's exact and log-rank tests . Venlafaxine XR produced significantly higher rates of sustained remission in depressed patients compared to fluoxetine/paroxetine or placebo over this 8-week treatment period . As early as week 2 , a significantly greater proportion of patients treated with venlafaxine  achieved improved depression scores ( remission and response ) . A significantly greater rate of remission and sustained remission  occurred with venlafaxine compared to placebo  . Remission was achieved earlier with venlafaxine and lasted throughout the remainder of the study . These results demonstrate that venlafaxine XR is more effective than fluoxetine/paroxetine for sustaining remission of depressive symptoms The current study was carried out to investigate the cognitive effects of two serotonin reuptake inhibitors ( SSRIs ) , sertraline and paroxetine , with special reference to differences in their affinity for other neurotransmitter systems , i.e. anticholinergic activity of paroxetine and putative dopamine reuptake activity of sertraline . The study was conducted according to a double-blind , three-way cross-over design . During three treatment periods of 2 weeks , 24 healthy middle-aged ( aged 30–50 years ) subjects of both sexes received sertraline ( 50 mg on days 1–7 , 100 mg on days 8–14 ) , paroxetine ( 20 mg on days 1–7 , 40 mg on days 8–14 ) and placebo . Paroxetine specifically impaired delayed recall in a word learning test at a dose of 20 and 40 mg . Sertraline did not affect word learning but improved performance on a verbal fluency task at a dose of 50 and 100 mg . Neither drug affected performance on a short-term memory scanning task . These subtle but significant changes in cognitive performance can be explained by subtle differences in pharmacological profiles of these SSRIs . The additional anticholinergic effects of paroxetine could account for its induction of long-term memory impairment . Similarly , the additional dopaminergic effects of sertraline could account for its induction of slightly improved verbal fluency . The impairing and facilitating cognitive effects of paroxetine and sertraline , respectively , may be more pronounced in the elderly depressed patient The acute efficacy of selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of major depressive disorder ( MDD ) is well established ; however their role in longer-term prevention of recurrence remains unconfirmed . This study aims at examining : the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up , the effect of concomitant cognitive behavioral therapy ( CBT ) , and the predictors of outcome . In a prospect i ve cohort study , 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine , escitalopram , sertraline and paroxetine-were  followed up over several years . During an average follow-up period of 34.5 months , 76.5 % of patients experienced MDD recurrence . Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant . The prophylactic efficacy for SSRI-only treatment was limited , with a recurrence rate of 82.0 % , compared to 59.0 % of patient recurrence rate in concomitant Cognitive Behavioral Therapy ( CBT ) . The relatively small size of the CBT group and the lack of r and omization may undermine the extrapolation of its findings to clinical practice . Nevertheless , the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence Chronic benzodiazepine ( BDZ ) users often have difficulty with BDZ withdrawal .  To examine clinical effects of selective serotonin reuptake inhibitor ( SSRI ) on tapering BDZ use in non-depressive patients , 97 out patients with a history of BDZ use for at least 3 months were recruited at an internal medicine clinic of a university hospital . After the 4th edition of the Diagnostic and Statistical Manual ( DSM-IV ) clinical interviews for screening major depression , 66 out patients ( 68 % ) without the DSM-IV major depression were r and omly assigned to one of three groups : SSRI-assisted BDZ-reduction group ( 10 - 20 mg of paroxetine , n = 22 ) , simple BDZ-reduction group ( no paroxetine , n = 23 ) , and reference group ( no BDZ-reduction , n = 21 ) . A st and ardized 8-week program involving gradual BDZ discontinuation was performed in the two BDZ-reduction groups . The Hamilton Rating Scales for Depression ( HAM-D ) and Anxiety ( HAM-A ) and the BDZ Withdrawal Symptom Question naire were assessed during the intervention period . Those with major depression were excluded from the BDZ-reduction intervention and treated with a different protocol of medication . In total , 10 ( 45.5 % ) in the SSRI-assisted BDZ-reduction group ( n = 22 ) succeeded in becoming BDZ-free after completing the program , whereas only four ( 17.4 % ) in the simple BDZ-reduction group ( n = 23 ) succeeded . The assistance of the SSRI significantly predicted the success of becoming BDZ-free ( P = 0.023 ) , controlling for the effects of age , gender , period of BDZ use , and baseline HAM-D and HAM-A scores . The score changes on the three question naires were comparable ( all P > 0.05 ) among the three groups during the intervention period . The use of SSRI may have beneficial effects on BDZ withdrawal without the worsening of mood states in cases without major depression Paroxetine , a selective serotonin reuptake inhibitor ( SSRI ) antidepressant , is considered to have fewer side-effects than a typical tricyclic antidepressant . As the elderly frequently suffer from adverse effects of psychotropic drugs , safeties and tolerance of paroxetine and their relationship with dose were studied in a double-blind study . Sixteen nondashhospitalised depressed patients , aged 72 - 86 years , were recruited but 12 patients completed the study . Patients were r and omly selected to receive either 15 mg or 30 mg paroxetine daily for 42 days in a double-blind study . A trained nurse made weekly home visits to monitor their medication and general conditions . Patients were assessed at the hospital on days 1 , 7 , 14 , 28 and 42 . There were four drop-outs during the first week of study due to lack of motivation , skin rash and upper gastrointestinal symptoms ( n=2 ) . Plasma levels of paroxetine  showed a dose-related increase in concentrations and indicated a good compliance . At the dosages used , no changes in blood pressure , heart rate , salivary volume , visual choice reaction time , critical flicker fusion threshold and short-term memory were observed in these patients . However , there was a significant improvement in their subjective symptoms ( as assessed by a symptom check list and Hamilton Rating Scale ) in the 30 mg group , indicating a feeling of well-being Paroxetine is a novel phenylpiperidine antide-pressant agent that acts as a potent and selective inhibitor of serotonin reuptake . We report results of a 6-week , r and omized , double-blind , multicenter study comparing paroxetine and fluoxetine in the treatment of major depression . One hundred seventy-eight in patients , who met DSM-III-R criteria for a major depressive episode and had a Montgomery Asberg Depression Rating Scale ( MADRS ) score of 24 or more , were included in the study . Their ages ranged from 18 to 65 years . Subjects were r and omized to receive either paroxetine or fluoxetine for 6 weeks . A 20-mg fixed dose , given once daily in the morning , was used for both drugs . After baseline , regular assessment s were made at the end of weeks 1,2,3,4 , and 6 . Efficacy measures included the MADRS , the Clinical Global Impression severity of illness scale , the Hamilton Rating Scale for Anxiety , the Hospital Anxiety and Depression scale , and the Visual Analogue Scale for anxiety . Safety and tolerability were assessed by adverse event reports , clinical examinations , vital signs , and laboratory data . A marked antidepressant response and good tolerability were seen with both drugs . These results further support the usefulness of paroxetine in the treatment of depressive illness OBJECTIVE The incidence of  sexual dysfunction  due to antidepressant drugs reported in pre-marketing clinical efficacy trials is often several times lower than in subsequent clinical experiences and independent reports . Although it is commonly believed that the reason for this discrepancy is that the nonleading questions employed in conventional clinical trials underestimate sexual dysfunction while the direct question ing used in independent trials provides more accurate data , few studies have actually compared these 2 methods . METHOD In this study , 119 patients with a DSM-IV-defined major depressive episode ( 82 women and 37 men ) who had been treated with but not responded to a selective serotonin reuptake inhibitor ( SSRI ; either citalopram or paroxetine )  were assessed regarding sexual functioning by means of open-ended questions and direct question ing at baseline ( after SSRI treatment only ) and after 4 weeks of SSRI treatment plus buspirone or placebo . RESULTS More patients reported sexual dysfunction in response to direct question ing ( 41 % ) as compared with spontaneous report ( 6 % ) ( p < .001 ) . Sexual dysfunction correlated with the duration of the depressive episode , but not with age , dose of SSRI , plasma level of SSRI , duration of SSRI treatment , or any measurement of depression . No statistically significant differences regarding the incidence of sexual dysfunction were found between the citalopram and the paroxetine groups . CONCLUSION Open-ended questions are an insufficient tool to estimate sexual dysfunction , and premarketing clinical trials should therefore include basic explicit assessment s. The failure to find a correlation between treatment duration and sexual dysfunction adds to the notion that sexual side effects due to SSRIs do not abate over time Abrupt interruption or cessation of selective serotonin reuptake inhibitor ( SSRI ) treatment may result in discontinuation or treatment interruption symptoms . Recent reports suggested these symptoms occur more frequently with shorter half-life SSRIs . Previous studies indicated a 5–8-day treatment interruption result ed in fewer discontinuation-emergent adverse events in  fluoxetine-treated patients than in paroxetine-treated patients . This study examines the effects of shorter treatment interruption ( 3–5 days ) , as would occur if patients miss just a few doses of medication . Patients successfully treated for depression with fluoxetine or paroxetine  underwent treatment interruption in a double-blind fashion . Treatment interruption-emergent symptoms were assessed using the Discontinuation-Emergent Signs and Symptoms checklist . Other assessment s included the Montgomery – Åsberg Depression Rating Scale , Clinical Global Impressions-Severity scale and a social functioning question naire . Of 150 patients enrolled , 141 completed the study . Following treatment interruption , fluoxetine-treated patients experienced fewer treatment interruption-emergent events than did paroxetine-treated patients . The paroxetine treatment group also experienced significant increases in depressive symptoms , clinical global severity scores and difficulty in social functioning ; the fluoxetine treatment group did not . These results are consistent with reports suggesting abrupt interruption of treatment with paroxetine is more often associated with somatic and psychological symptoms than is abrupt interruption of fluoxetine . Patients treated with fluoxetine appeared to be protected by its longer half-life To underst and the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression , we conducted a r and omized , double-blind , placebo-control head-to-head comparison of maprotiline ( a norepinephrine reuptake blocker ) and paroxetine ( a serotonin reuptake blocker ) in 103 patients with chronic low back pain . Of these 74 completed the trial ; of the 29 who did not complete , 19 were withdrawn because of adverse effects . The intervention consisted of an 8-week course of maprotiline ( up to 150 mg daily ) or paroxetine ( up to 30 mg daily ) or an active placebo , diphenhydramine hydrochloride ( up to 37.5 mg daily ) . Patients were excluded for current major depression .  Reduction in pain intensity ( Descriptor Differential Scale scores ) was significantly greater for study completers r and omized to maprotiline compared to placebo ( P=0.023 ) , and to paroxetine ( P=0.013 ) , with a reduction of pain by 45 % compared to 27 % on placebo and 26 % on paroxetine . These results suggest that at st and ard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors BACKGROUND Bipolar depression is a major clinical problem that remains under- research ed . The current study was intended to evaluate the effects of the novel antipsychotic risperidone , the selective serotonin reup-take inhibitor ( SSRI ) paroxetine , and the combination in patients with bipolar disorder . METHOD Thirty patients with DSM-IV bipolar ( I or II ) disorder , depressed phase , who were receiving a stable dose of a mood stabilizer were r and omly assigned to 12 weeks of double-blind treatment with risperidone ( plus placebo ) , paroxetine ( plus placebo ) , or the combination of risperidone and paroxetine . Data were gathered from August 1999 to September 2001 . RESULTS All 3 groups experienced significant reductions in depression ratings from baseline to endpoint ; there were no significant differences in outcome between groups . There were statistically significant differences in paroxetine dose contrasting paroxetine plus placebo against the combined condition . The switch rate into mania or hypomania was very low , with only 1 patient in the paroxetine plus placebo condition experiencing mild hypomania . CONCLUSION These results suggest that risperidone , paroxetine , and the combination of risperidone and paroxetine are equally but modestly effective when added to a mood stabilizer in bipolar depression . The paroxetine dose differed between groups , possibly because of drug-drug interactions . Using another SSRI in the combined condition could have produced a more robust effect and should be tested Depressed mood has been associated with reduced natural killer cell activity ( NKCA ) . Further , amelioration of depressive symptoms by pharmacotherapy has result ed in augmented NKCA . Serotonin , an indoleamine implicated in the pathophysiology of affective disorders , enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors . The present study evaluated NKCA  in depressed out patients before and during treatment with the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine ( Prozac ® ) . Further , the SSRIs , fluoxetine and paroxetine ( Paxil ® ) , were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA . Depressed out patients were administered fluoxetine  ( 20 mg/day ) for 4 weeks  . NKCA and severity of depression were evaluated at weeks 0 , 1 , 2 , and 4 . Serum concentrations of fluoxetine and norfluoxetine were obtained as well . Mononuclear cells obtained from nonpatient volunteers were incubated with pharmacologic concentrations of fluoxetine or paroxetine and NKCA measured with a st and ard chromium release assay . Fluoxetine treatment result ed in decreased symptoms of depression and increased serum concentrations of fluoxetine and norfluoxetine  . Further , fluoxetine treatment was associated with augmented NKCA in a subgroup of depressed out patients exhibiting low NKCA at baseline . Fluoxetine had no effect on NKCA in depressed individuals exhibiting high NKCA at baseline . Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro . The enhancing effects of antidepressants on NKCA in vivo and in vitro indicate a possible direct drug interaction with lymphoid cells during pharmacotherapy , suggesting that pharmacologic treatment of depression may result in enhanced immune competence as indexed by enhanced NKCA and that NKCA could be pharmacologically augmented with antidepressants in individuals with compromised immune function CONTEXT Major depressive disorder causes significant morbidity and mortality . Current therapies fail to fully treat both emotional and physical symptoms of major depressive disorder . OBJECTIVE To evaluate duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , on improvement of emotional and painful physical symptoms . DESIGN R and omized , double-blind , evaluation of duloxetine at 40 mg/d ( 20 mg twice daily ) and 80 mg/d ( 40 mg twice daily ) versus placebo and paroxetine 20 mg/d in depressed out patients . MAIN OUTCOME MEASURES The primary efficacy measure was the 17-item Hamilton Depression Rating Scale . Visual Analog Scales for pain , Clinical Global Impression of Severity , Patient 's Global Impression of Improvement , and Quality of Life in Depression Scale were also used . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests . RESULTS Duloxetine 80 mg/d was superior to placebo on mean 17-item Hamilton Depression Rating Scale total change by 3.62 points ( 95 % CI 1.38 , 5.86 ; P = 0.002 ) . Duloxetine at 40 mg/d was also significantly superior to placebo by 2.43 points ( 95 % CI 0.19 , 4.66 ; P = 0.034 ) , while paroxetine was not ( 1.51 points ; 95 % CI -0.55 , 3.56 ; P = 0.150 ) . Duloxetine 80 mg/d was superior to placebo for most other measures , including overall pain severity , and was superior to paroxetine on 17-item Hamilton Depression Rating Scale improvement ( by 2.39 points ; 95 % CI 0.14 , 4.65 ; P = 0.037 ) and estimated probability of remission ( 57 % for duloxetine 80 mg/d , 34 % for paroxetine ; P = 0.022 ) . The only adverse event reported significantly more frequently for duloxetine 80 mg/d than for paroxetine was insomnia ( 19.8 % for duloxetine 80 mg/d , 8.0 % for paroxetine ; P = 0.031 ) . Hypertension incidence was not affected by any treatment . CONCLUSION Duloxetine therapy was efficacious for emotional and physical symptoms of depression , with a selective serotonin reuptake inhibitor-like profile of side effects Paroxetine is a selective serotonin reuptake inhibitor with significant antidepressant properties . This was a 6-week placebo- and imipramine-controlled study of 120 out patients with major depression .  Paroxetine was statistically significantly superior to placebo on almost all outcome measures . This was apparent as early as 1 week . Paroxetine was also significantly superior to imipramine on the Hamilton Rating Scale for Depression total score .  Paroxetine was generally better tolerated than imipramine . These results strongly support paroxetine 's effectiveness in the treatment of major depression and suggest that paroxetine will be a valuable addition to the options in treating depressive illness BACKGROUND Social phobia , also known as social anxiety disorder , is a highly prevalent disorder with significant morbidity . Patients with social phobia frequently develop co-morbid psychiatric disorders such as depression and substance abuse , and the disorder impacts significantly on social and occupational functioning . It has been suggested that the selective serotonin reuptake inhibitors ( SSRIs ) are useful in the management of this disorder , but few controlled trials have been undertaken in this regard . There are also few data on the pharmacotherapy of social phobia in South Africa . METHODS A double-blind r and omised placebo-controlled multi-site flexible-dose trial of paroxetine was undertaken over 12 weeks among patients with a primary diagnosis of social phobia . Primary response measures were the Global Improvement item on the Clinical Global Impression scale ( CGI ) and mean change from baseline in the patient-rated Liebowitz Social Anxiety Scale ( LSAS ) total score .  Ninety-three patients participated at 9 South African sites ; their data are reported here . RESULTS There was a significant drug effect on both the CGI Global Improvement score and the LSAS at 12 weeks . In addition , there was no significant difference in overall rate of adverse experiences between those on paroxetine and those on placebo . CONCLUSIONS Paroxetine is both effective and safe in the acute treatment of social phobia . The findings here are consistent with those of previous controlled studies of the SSRIs as well as with previous work done in the USA on the use of paroxetine in the treatment of this disorder . Early diagnosis and treatment of social phobia should be encouraged . However , further research on long-term pharmacotherapy of social phobia is needed Selective serotonin reuptake inhibitor (SSRI)-induced nausea can be severe enough to lead to early treatment discontinuation . However , it is currently not possible to predict the occurrence of nausea before the initiation of SSRI treatment . In this study , we investigated the effect of genetic polymorphisms in the 5-hydroxytryptamine type 2A , 3A , and 3B ( 5-HT3B ) receptors , 5-HT transporter , and CYP2D6 genes on the incidence of  paroxetine-induced nausea . A consecutive series of 72 Japanese patients with depressive or anxiety disorders were treated with paroxetine . Paroxetine-induced nausea was assessed by a pharmacist and was observed in 29.2 % of the patients . A significant ( nominal p=0.00286 ) association was found between the incidence of nausea and the -100_-102AAG insertion/deletion polymorphism of the 5-HT3B receptor gene . No significant associations were observed between the other genetic polymorphisms and the incidence of nausea . The -100_-102AAG deletion variant of the 5-HT3B receptor gene may affect paroxetine-induced nausea Impaired cognitive functioning is often associated with major depressive disorder ( MDD ) . Moreover , a number of agents used to treat MDD are known to have negative effects on cognitive functioning . We report an assessment of the effects of the selective norepinephrine reuptake inhibitor reboxetine , the selective serotonin reuptake inhibitor paroxetine , and placebo on a variety of measures of cognitive functioning in patients with MDD.Cognitive  functioning in 74 adult patients ( aged 18–65 years ) with a confirmed diagnosis of MDD ( DSM-IV ) was assessed as part of two identical , r and omized , double-blind , placebo- and active-treatment-controlled , fixed/flexible dose comparisons of 8 weeks of treatment with reboxetine ( 8–10 mg/day ) , paroxetine ( 20–40 mg/day ) and placebo .  Cognitive function was assessed at baseline , day 14 and day 56 using a selection of tasks from the Cognitive Drug Research computerized assessment system , including Simple Reaction Time , Digit Vigilance , Choice Reaction Time , Numeric Working Memory , Word Recognition and Critical Flicker Frequency . The results in the 74 patients  ( reboxetine n = 25 , paroxetine n = 23 , placebo n = 26 ) showed that reboxetine significantly improved the ability to sustain attention at day 56 compared with baseline ( P = 0.023 ) . In addition , patients who received reboxetine experienced significant improvements in their speed of cognitive functioning when tested at day 56 compared to baseline ( P = 0.024 ) . No significant changes or trends in this direction were seen among patients who received either placebo or paroxetine . The results of the present study provide objective data to support the possibility that reboxetine favourably affects cognitive processes in depressed patients CONTEXT Selective serotonin reuptake inhibitors ( SSRIs ) are the most commonly prescribed class of antidepressant , yet it is not known whether one SSRI is more effective than another . OBJECTIVE To compare the effectiveness of 3 SSRIs ( paroxetine , fluoxetine , and sertraline ) in depressed primary care patients . DESIGN Open-label , r and omized , intention-to-treat trial , with patient enrollment occurring in April-November 1999 . SETTING Thirty-seven clinics in 2 US primary care research networks . PATIENTS A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 189 ) , fluoxetine ( n = 193 ) , or sertraline ( n = 191 ) for 9 months . Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI . MAIN OUTCOME MEASURES The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) Mental Component Summary score ( range , 0 - 100 ) , compared across treatment groups at 1 , 3 , 6 , and 9 months . Secondary outcomes included other depression and psychological measures , multiple measures of social and work functioning , and other domains of health-related quality of life , such as physical functioning , concentration and memory , vitality , bodily pain , sleep , and sexual functioning . RESULTS Follow-up interviews were successfully completed in 94 % of patients at 1 month , 87 % at 3 months , 84 % at 6 months , and 79 % at 9 months . Responses to the 3 SSRIs were comparable on all measures and at all time points . The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group , + 15.1 in the fluoxetine group , and + 17.4 in the sertraline group . The drugs were also associated with similar incidences of adverse effects and discontinuation rates . CONCLUSIONS The SSRI antidepressants paroxetine , fluoxetine , and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial OBJECTIVE The authors sought to identify genetic markers for antidepressant medication intolerance . Genetic variation in drug metabolizing enzymes such as cytochrome P450 2D6 ( CYP2D6 ) has been postulated to underlie antidepressant intolerance ( pharmacokinetic effect ) . However , variation in genes encoding serotonin receptors could also explain antidepressant side effects ( pharmacodynamic effect ) . METHOD An 8-week , double-blind , r and omized pharmacogenetic study compared the widely prescribed antidepressants paroxetine ( a selective serotonin reuptake inhibitor [ SSRI ] ) and mirtazapine ( not an SSRI ) in 246 elderly patients with major depression . Genotypes were determined for the 102 T/C single nucleotide polymorphism ( SNP ) in the serotonin 2A ( 5-HT(2A ) ) locus ( HTR2A ) , previously associated with psychotropic medication treatment outcome . Oligonucleotide microarrays were used to extensively characterize variation in the CYP2D6 gene . Clinical outcomes included treatment discontinuations , adverse events , medication compliance , and change in mood . RESULTS Survival analysis showed discontinuations due to paroxetine-induced side effects were strongly associated with the HTR2A C/C genotype . There was a significant linear relationship between the number of C alleles and the probability of discontinuation . Side effect severity in paroxetine-treated patients with the C/C genotype was also greater . In contrast , HTR2A 102 T/C genotype had no effect on mirtazapine side effects . CYP2D6 genotype did not predict treatment outcome for either medication . CONCLUSIONS Pharmacodynamic differences among patients due to variant 5-HT(2A ) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance . Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram , in the treatment of major depressive disorder ( MDD ) . In total , 357 out patients with MDD were r and omized to treatment with reboxetine 8 - 10 mg or citalopram 20 - 40 mg per day during 24 weeks . Primary end-point was change from baseline in the Hamilton Depression Rating Scale ( HAM-D , 21 items ) . Sexual function/dysfunction was measured by the Sexual Function scale ( SF ) . Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores : reboxetine with -21.4 and citalopram with -22.1 points ( NS ) . LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine ( -19.6 vs. -17.8 ; P = 0.034 ) . The response rate was 90.3 % for reboxetine and 92.7 % for citalopram ( NS ) . The most common side effect in the reboxetine group was dry mouth , and in the citalopram group sexual dysfunction . At week 24 , anorgasmia was reported by 5.9 % of the sexually active women in the reboxetine group vs 39 % in the citalopram group . The  dropout number  was 91 in the  reboxetine group , and 54 in the citalopram group . To summarize , both treatments gave a satisfactory antidepressant effect . The side effect profile differed between the groups , with a notably high prevalence of sexual dysfunctions in the citalopram group . The high number of dropouts in the reboxetine group , is considered as a result of the non-titration starting dose of 8 mg reboxetine per day , which gave a high incidence of early side-effects .  Depressive disorders including major depression ( MDD ) is very common , with a lifetime prevalence of at least 15 % in men and 25 % in women.1,2 Depression can be treated effectively by a range of antidepressant agents . Recent review s have suggested that the selective serotonin reuptake inhibitors ( SSRIs ) offer equal efficacy to the older antidepressant agents , such as tricyclic antidepressants , with the advantage of greater tolerability.3 - 5 Other review ers have reported that non-SSRI antidepressants , such as clomipramine , have been found to be significantly more effective than fluoxetine for the treatment of patients with severe depression.6  Reboxetine ( reboxetine mesylate , Edronax ; Pfizer , New York ) is a highly selective noradrenaline reuptake inhibitor , and the efficacy of reboxetine has been independently demonstrated in multiple r and omized , double-blind , placebo-controlled studies .7 - 9 In addition to improvements in depressive symptoms , treatment-associated improvements in social behavior ( measured using the Social Adaptation Self-evaluation Scale [SASS]),10 were noticed in one of these studies .8 In this study , reboxetine was statistically and clinical ly superior to both placebo and fluoxetine in improving social functioning . The primary objective of the current study was to assess efficacy and tolerability of reboxetine  in comparison with those of citalopram ( Cipramil ; H. Lundbeck , Copenhagen , Denmark ) in patients with MDD .  Citalopram is a highly SSRI . The antidepressant mechanism is presumed to be a result of stimulation of serotonergic neurotransmission in the central nervous system as a consequence of higher serotonin levels result ing from inhibition of the serotonin transporter . The therapeutic efficacy of citalopram in patients with MDD has been investigated in several placebo-controlled studies and in long-term and extension studies .11 The underlying rationale for this comparison was to study 2 different drug profiles , 1 drug being pure " adrenergic " and the other pure " serotonergic . " A secondary objective was to analyze the correlation between the types of depression ( ie , degree of melancholia and the efficacy of the 2 drugs ) Objectives : Selective serotonin reuptake inhibitors ( SSRIs ) are currently considered as the first drug of choice in the treatment of panic disorder ( PD ) . The aim of this long-term , naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD . Outcome measures included relapse rates and adverse effects . Methods : Two hundred patients with PD were enrolled in our study . All subjects met DSM-IV criteria for PD or PD with agoraphobia ( PDA ) . All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram ( n = 50 ) , fluoxetine ( n = 50 ) , fluvoxamine ( n = 50 ) , or paroxetine ( n = 50 ) in a r and omized , nonblinded fashion . Both the treating psychiatrist and the patients were not blind to the assigned treatment , but the clinician raters were blind to the study medication . The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists . The Panic Self- Question naire , which is a self-report scale , was administered at baseline and then once per month during the duration of the 12-month study . The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study . Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits . The body weight of study subjects was measured at baseline , and then at the 12th month visit end point . Results : Of 200 patients who entered the study , 127 patients ( 63.5 % ) completed the full 12-month protocol . Retention rates were highest for paroxetine ( 76 % [ 38/50 ] ) , intermediate for citalopram ( 68 % [ 34/50 ] ) and fluvoxamine ( 60 % [ 30/50 ] ) , and lowest for fluoxetine ( 50 % [ 25/50 ] ) . Patients who completed the 12-month protocol responded favorably to the study treatment . The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8 . At visits on months 3 , 6 , 9 , and 12 , however , there were no statistically significant differences between the 4 groups in relapse rates ( defined as the occurrence of 1 or more panic attacks during the previous week of treatment ) ( F1,127 = 0.17 ; P = 0.13 [ not statistically significant ] ) . At the 12th month end point , patients in all 4 treatment groups had a statistically significant increase in body weight . Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment . Reports of sexual adverse effects at the 12th month visit were similar in the citalopram , fluoxetine , and paroxetine groups , but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit . Conclusions : Most of our PD patients responded well to 12-month treatment with either citalopram , fluoxetine , fluvoxamine , or paroxetine , and the overall response rate was equal after the first 4 weeks of treatment . Although patients treated with paroxetine had the lowest dropout rates during the initiation phase , they had the highest rate of adverse effects as measured at the 12th month visit . Conversely , patients in the fluvoxamine group had the highest dropout rate ( which was primarily caused by adverse effects in the initiation phase of treatment . ) ; however , patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents . Overall , when measured at the 12th month visit , monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine . In addition , monotherapy with paroxetine , citalopram , and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine In this study , we tested the influence of the serotonin type 2A , 3A and 3B receptor genes ( HTR2A , HTR3A , HTR3B ) in addition to a polymorphism in the promoter region of the serotonin transporter ( SERTPR ) , and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine . A total of 100 Japanese patients affected by major recurrent depression were enrolled in a r and omized 6-week study . The clinical response was evaluated using the Hamilton Rating Scale for Depression ( HAM-D ) , and adverse drug reactions were assessed at each visit . Patients with the l allele of SERTPR showed a better response to SSRIs than s/s genotype carriers ( p = 0.015–0.042 ) , more significantly to fluvoxamine . The –1438G/G genotype of HTR2A was associated with a good response to SSRIs ( p = 0.010–0.039 ) , especially to fluvoxamine , and significantly with severe nausea in paroxetine-treated patients ( p = 0.013 ) . The 178C/C genotype of the HTR3A was associated with an antidepressant response ( p = 0.022–0.042 ) , and more significantly in paroxetine-treated patients ( p = 0.002–0.042 ) . These effects were independent of one another . We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs . We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy , and the HTR2A polymorphism is also associated with adverse drug reactions . Furthermore , the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI & NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine  30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors Objective : To test the hypothesis that in patients with major depressive disorder ( MDD ) , the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors ( SSRIs ) and that patterns of response will differ based on symptom severity at baseline . Method : Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD : 7 r and omized , double-blind , fixed-dose , 8-week studies of duloxetine  ( n = 1,133 )  versus SSRI  ( n = 689 )  versus placebo  ( n = 641 ) .  Duloxetine doses were 40 , 60 , 80 and 120 mg/day . SSRI doses were 10 mg/day ( escitalopram ) and 20 mg/day ( fluoxetine and paroxetine ) . Results : Compared to SSRI-treated patients , duloxetine-treated patients had a significantly greater ( p ≤ 0.05 ) reduction in the 17-item Hamilton Depression Rating Scale ( HAMD17 ) total score and HAMD17 items of work and activities , psychomotor retardation , genital symptoms and hypochondriasis . Differences favoring the SSRIs approached significance for middle insomnia ( p = 0.057 ) and late insomnia ( p = 0.06 ) , with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine . Similarly , the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms ( p = 0.056 ) , with an effect size twice that observed for the SSRIs . The HAMD17 total score difference was driven mostly by patients with lower baseline MDD severity ( HAMD17 total score ≤19 ) , where the HAMD17 effect size advantage for duloxetine over combined SSRIs was statistically significant ( p = 0.031 ) . Conclusion : Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity , and different HAMD17 items responded differently to duloxetine compared with SSRIs . Underst and ing these differences may be useful in tailoring antidepressant therapy for individual patients reuptake inhibitors ( SSRIs ) during continuation therapy . This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression , quality of life , and personality outcomes .  Out patients with unipolar major depression ( DSM-III-R ) were r and omly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine ( 20 - 40 mg ) or sertraline ( 50 - 150 mg ) . Assessment s included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression Scale , the Battelle Quality of Life Question naire , and the Structured Clinical Interview for DSM-III-R Personality Disorders screen question naire . One hundred seventy-six patients ( mean age , 43 years ; 64 % female ; baseline MADRS , 30.3 ) were treated with sertraline and 177 patients ( mean age , 42 years ; 71 % female ; MADRS , 30.7 ) with paroxetine .  Antidepressant efficacy during continuation therapy was sustained , with only 2 % of patients receiving sertraline and 9 % of patients receiving paroxetine suffering a relapse . Continuation therapy result ed in a substantial conversion of responders during short-term treatment to full remission : remitter rates increased from 52 % to 80 % for sertraline and from 57 % to 74 % for paroxetine . The improvements in quality of life were related to a reduced depression score .  SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality . A logistic regression analysis identified early response ( 25 % reduction in MADRS scores at week 2 ) as the most important predictor of treatment response , whereas high severity , chronicity , and poor baseline quality of life had no effect . Both treatments were well-tolerated , with sertraline having a somewhat lower side effect profile .  Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy . Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology Depressive disorders are a major health care issue and one of the foremost causes of disability in adults around the world , result ing in significant costs to society and health care systems ( 1 ) . The estimated economic burden associated with depression was $ 83.1 billion in 2000 and is probably higher today ( 2 ) . Depressive disorders include major depressive disorder ( MDD ) ; dysthymia ; and subsyndromal depression , including minor depression . Major depressive disorder is the most prevalent depressive disorder , with an estimated lifetime prevalence of 16 % in the United States ( 3 ) . An average of 8 million ambulatory care visits per year result in a primary diagnosis of MDD ( 4 ) . The American Psychiatric Association ( 5 ) defines MDD as depressed mood or loss of pleasure or interest along with other symptoms , including significant change in weight or appetite , insomnia or hypersomnia , psychomotor agitation or retardation nearly every day , fatigue or loss of energy , feelings of worthlessness or excessive or inappropriate guilt , indecisiveness or decreased ability to concentrate , and recurrent thoughts of death or suicide , that last for at least 2 weeks and affect normal functioning . Dysthymia is less severe , but symptoms last for 2 or more years . In contrast , subsyndromal depression is associated with less severe symptoms of depression that do not qualify for MDD or dysthymia diagnoses . The treatment of depression can be characterized by 3 phases ( Figure 1 ) : acute ( 6 to 12 weeks ) , continuation ( 4 to 9 months ) , and maintenance ( 1 year ) ( 7 ) . Relapse is defined as the return of depressive symptoms during the acute or continuation phases and is therefore considered part of the same depressive episode , whereas recurrence is defined as the return of depressive symptoms during the maintenance phase and is considered a new , distinct episode . Response to treatment ( typically defined as 50 % reduction in measured severity ) can be quantified using various tools , such as the Patient Health Question naire-9 ( PHQ-9 ) ( 7 ) or the Hamilton Depression Rating Scale ( HAM-D ) ( 8) . Figure 1 . Phases of treatment of major depression . Adapted from reference 6 . TX = treatment . Various treatment approaches can be used to manage MDD , such as psychotherapy , complementary and alternative medicine ( CAM ) , exercise , and pharmacotherapy . The psychological interventions used to treat depression include acceptance and commitment therapy , cognitive therapy , cognitive behavioral therapy ( CBT ) , interpersonal therapy , and psychodynamic therapies ( Table 1 ) . The CAM treatments include acupuncture , meditation , -3 fatty acids , S-adenosyl-l-methionine ( SAMe ) , St. John 's wort , and yoga . Exercise includes a broad range of activities that can be done for varying duration s , in classes , individually , or in informal groups . For pharmacologic therapy , the scope of this guideline is limited to second-generation antidepressants ( SGAs ) ( selective serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , and selective serotonin norepinephrine reuptake inhibitors ) . First-generation antidepressants ( tricyclic antidepressants and monoamine oxidase inhibitors ) are very rarely used because SGAs have lower toxicity in overdose than first-generation antidepressants and similar efficacy . Table 1 . Common Psychological Interventions to Treat Depression Guideline Focus and Target Population The purpose of this guideline from the American College of Physicians ( ACP ) is to summarize and grade the evidence on the comparative effectiveness and safety of nonpharmacologic treatments and SGAs ( including serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , bupropion , mirtazapine , nefazodone , and trazodone ) , alone or in combination , for MDD . The target audience for this guideline includes all clinicians , and the target patient population includes all adults with MDD . These recommendations are based on a background evidence article ( 9 ) and a systematic evidence review sponsored by the Agency for Healthcare Research and Quality ( AHRQ ) ( 6 ) . Methods Systematic Review of the Evidence The systematic evidence review was conducted by the AHRQ 's RTI InternationalUniversity of North Carolina at Chapel Hill Evidence -based Practice Center ( 6 ) . Additional method ological details can be found in the Appendix ) , accompanying background evidence article ( 9 ) , and full report ( 6 ) . Review ers search ed several data bases for studies published in English , German , or Italian from 1 January 1990 through September 2015 . Studies on efficacy were limited to r and omized , controlled trials and systematic review s and meta-analyses , although evidence on harms included observational studies . Review ers combined data when possible using meta- analysis and assessed the risk of bias and quality of studies according to established methods . The study population included adult out patients ( aged 18 years ) with MDD during either an initial or a second treatment attempt who did not remit after an initial adequate trial with an SGA . The review evaluated the following classes of interventions : depression-focused psychotherapy , CAM , exercise , and SGAs . Outcomes assessed included benefits in response ( often defined as 50 % improvement in HAM-D scores ) , remission ( often defined as a HAM-D score 7 ) , speed of response , speed of remission , relapse , quality of life , functional capacity ( as assessed by various scales ) , reduction of suicidality , or reduction of hospitalization . Harms assessed included overall adverse events , withdrawals because of adverse events , serious adverse events , and specific adverse events . Quality of life , functional status , suicidality , and hospitalizations were rarely reported . Grading the Evidence and Developing Recommendations This guideline was developed by the ACP Clinical Guidelines Committee according to the ACP guideline development process , which has been described ( 10 ) . The Clinical Guidelines Committee used the evidence tables in the accompanying systematic review and full report ( 9 ) when reporting the evidence and grade d the recommendations using ACP 's guideline grading system ( Table 2 ) . Table 2 . The American College of Physicians ' Guideline Grading System * Peer Review The AHRQ evidence review was sent to invited peer review ers and posted on the AHRQ Web site for public comments . The guideline was peer- review ed through the journal and was posted online for comments from ACP Governors and Regents . Comparative Benefits of Pharmacologic Versus Nonpharmacologic Treatment Options for Initial Management Refer to Appendix Table 1 and the accompanying systematic review ( 9 ) for additional details of the evidence . Appendix Table 1 . First-Line Treatment for MDD : SGAs Versus Nonpharmacologic Therapies * SGA Versus Psychological Interventions SGA Versus CBT Monotherapy . Moderate- quality evidence from 5 trials ( 1115 ) showed no difference in response when comparing SGAs ( fluoxetine , fluvoxamine , paroxetine , or sertraline ) with CBT in patients with MDD after 8 to 52 weeks of treatment . Low- quality evidence from 3 trials ( 11 , 14 , 15 ) showed no difference between remission rates ( fluoxetine , fluvoxamine , and paroxetine ) and functional capacity ( 14 ) ( fluvoxamine and paroxetine ) for SGAs compared with CBT . Combination Therapy . Low- quality evidence from 2 trials ( 14 , 16 ) showed no difference in response or remission when comparing monotherapy using SGAs ( escitalopram , fluvoxamine , or paroxetine ) with combination therapy using SGAs plus CBT ( problem-solving therapy or telephone-based CBT ) in patients with MDD after 12 to 52 weeks of treatment . Low- quality evidence from 2 trials ( 14 , 16 ) assessed function , and 1 trial showed that patients who received the combination therapy reported more improvement on 3 of 5 work-functioning measures than those who received SGA monotherapy , although clinical ly important differences on these measures are uncertain . SGA Versus Interpersonal Therapy Monotherapy . Low- quality evidence showed no difference in response ( 1 trial ; escitalopram ) ( 17 ) or remission ( 2 trials ; citalopram , escitalopram , or sertraline ) ( 17 , 18 ) for SGAs compared with interpersonal therapy for patients with MDD after 12 weeks of treatment . Combination Therapy . Low- quality evidence from 1 trial ( 19 ) showed increased remission for SGA monotherapy compared with SGA combined with interpersonal therapy ( with nefazodone ) in patients with MDD after 12 weeks of treatment . SGA Versus Psychodynamic Therapies Monotherapy . Low- quality evidence from 1 trial ( 20 ) showed no difference in remission for fluoxetine compared with psychodynamic monotherapy in patients with MDD after 16 weeks of treatment . Low- quality evidence from 2 trials ( 20 , 21 ) showed few differences in functional capacity between the treatments . Combination Therapy . Low- quality evidence from 1 trial ( 21 ) showed no difference in functional capacity for SGA monotherapy compared with SGA plus psychodynamic combination therapy . SGA Versus CAM Interventions SGA Versus Acupuncture Monotherapy . Low- quality evidence from 2 trials ( 22 , 23 ) showed no difference in treatment response when comparing fluoxetine with acupuncture monotherapy for patients with MDD after 6 weeks of treatment . Combination Therapy . Low- quality evidence from 2 trials ( 24 , 25 ) showed that combination therapy of SGAs with acupuncture improved treatment response compared with monotherapy with SGAs ( fluoxetine or paroxetine ) in patients with MDD after 6 weeks of treatment . However , low- quality evidence from 1 trial ( 24 ) showed no difference in remission when comparing paroxetine monotherapy with paroxetine plus acupuncture combination therapy . SGA Versus -3 Fatty Acids Monotherapy . Low- quality evidence from network meta- analysis showed that SGAs ( fluoxetine ) were associated with a greater response than -3 fatty acids in patients with MDD .  SGA Versus SAMe Monotherapy . Low- quality evidence from network meta- analysis showed no difference in response between treatment with escitalopram BACKGROUND This study was design ed to evaluate the effect of combining bupropion sustained release ( SR ) with venlafaxine , paroxetine , or fluoxetine in patients who reported unacceptable sexual dysfunction when treated with monotherapy with the latter 3 agents . METHOD Following a minimum of 6 weeks of antidepressant treatment with a selective serotonin reuptake inhibitor ( SSRI ) or venlafaxine ( a serotonin-norepinephrine reuptake inhibitor ) , eligible subjects received a further 8 weeks of monitored combination therapy with bupropion SR at a dose of 150 mg/day with no alterations to index antidepressant dosing . RESULTS There was a clinical ly significant benefit in 14 ( 78 % ) of 18 partial responders or nonresponders , and 33 % ( N = 6 ) achieved a full response ( chi2= 8.06 , df = 2 , p = .017 ) . Sexual dysfunction , particularly a decrease in orgasmic delay , was also significantly improved with combination therapy ( men : paired t = -2.1 , df = 6 , p = .08 ; women : paired t = -3.0 , df = 7 , p = .02 ) . Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels ( F = 6.89 , df = 4,24 ; p = .001 ) accompanied by a decrease in O-desmethylvenlafaxine ( F = 14.26 ; df = 4,24 ; p < .0005 ) during combined treatment with bupropion SR . There were no statistically significant changes in plasma levels of SSRIs ( paroxetine and fluoxetine ) during the trial . CONCLUSION Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs . Further investigation of combination treatments under r and omized , double-blind conditions is recommended BACKGROUND Major depression with high levels of anxiety ( anxious depression ) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment . It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors . For this reason , using head-to-head acute treatment comparison , we compared efficacy and tolerability of fluoxetine , sertraline , and paroxetine among depressed patients with high levels of anxiety . METHODS Patients ( N = 108 ) with DSM-IV major depression and high levels of anxiety ( a HAM-D-Anxiety/Somatization Factor score > or = 7 ) were r and omized to fluoxetine , sertraline , or paroxetine treatment in a double-blind fashion . Changes in overall depression and anxiety were assessed . RESULTS Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores . Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores , except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score . There were no significant differences across treatments in percentages of patients with substantial emergence , any worsening , or improvement at endpoint in individual HAM-D Items 9 ( agitation ) , 10 ( psychic anxiety ) , and 11 ( somatic anxiety ) . Overall , all treatments were well tolerated . CONCLUSION These data showed no significant differences in efficacy and tolerability of fluoxetine , sertraline , and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression . Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression We reported an independent association of the short variant of the serotonin transporter gene‐linked polymorphic region ( SERTPR ) and tryptophan hydroxylase ( TPH ) genes with antidepressant response to  selective serotonin reuptake inhibitors ( SSRIs ) . The aim of the present study was to confirm the effect of the SERTPR and TPH gene variants on the  SSRIs antidepressant activity in a new sample of major and bipolar depressives . Two hundred and twenty one in patients ( major depressives = 128 , bipolar disorder = 93 ) were treated with SSRIs ( fluvoxamine or paroxetine ) for 6 weeks ; the severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression ( HAMD ) . SERTPR and TPH variants were determined using PCR‐based techniques , 220 subjects genotyped for SERTPR and 221 for TPH that were never included in previous studies . SERTPR*s/s variant association with a poor response to SSRI treatment was confirmed , even if with less significant P values ( P = 0.034 ) , independently from clinical variables ; pooling the present sample with previous ones we observed a highly significant effect ( P < 0.000001 ) . TPH*A/A variants showed higher HAMD scores throughout the trial but with only a trend in the same direction of our previous study in terms of a worse response of A/A genotypes . Thus , the previous positive association was not fully replicated for TPH . The present independent replication confirms SERTPR variants as a liability factor for antidepressant efficacy while the TPH effect is not unequivocal . © 2004 Wiley‐Liss , OBJECTIVE To evaluate the efficacy and safety of mirtazapine in depressed out patients who have shown nonresponse or intolerance to selective serotonin reuptake inhibitor ( SSRI ) therapy . METHOD In this open-label , 8-week study , the efficacy and safety of mirtazapine among 103 out patients with DSM-IV major depressive disorder who had failed previous therapy with an SSRI ( fluoxetine , paroxetine , or sertraline )  were evaluated . The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) , and safety assessment s included reported adverse events , routine laboratory assessment s , physical examinations , and assessment s of vital signs . A 4-day washout period followed by mirtazapine treatment was compared with an immediate switch from the SSRI to mirtazapine . RESULTS Based on mean HAM-D-17 scores at endpoint and response rates of 48 % based on the criterion of > or = 50 % reduction in HAM-D-17 score , mirtazapine was found to be an effective treatment for a substantial proportion of patients for whom an SSRI was ineffective and /or poorly tolerated . Mirtazapine was well tolerated , with sedation and appetite increase/weight gain the most commonly reported adverse events . In addition , no difference in efficacy , safety , or tolerability was observed for patients undergoing an immediate switch from an SSRI ( after having been tapered to the minimal effective dose ) to mirtazapine , compared with those undergoing the imposition of a 4-day drug-free washout . CONCLUSION These results suggest that an immediate switch to mirtazapine may be a valid therapeutic option among patients who can not tolerate or do not respond to SSRIs We examined allelic polymorphisms of the serotonin transporter ( 5-HTT ) gene and antidepressant response to 6 weeks ' treatment with the selective serotonin reuptake inhibitor ( SSRI ) drugs fluoxetine or paroxetine . We genotyped 120 patients and 252 normal controls , using polymerase chain reaction of genomic DNA with primers flanking the second intron and promoter regions of the 5-HTT gene . Diagnosis of depression was not associated with 5-HTT polymorphisms . Patients homozygous I/I in intron2 or homozygous s/s in the promoter region showed better responses than all others ( p < 0.0001 , p = 0.0074 , respectively ) . Lack of the I/I allele form in intron 2 most powerfully predicted non-response ( 83.3 % ) . Response to SSRI drugs  is related to allelic variation in the 5-HTT gene in depressed Korean patients BACKGROUND Many patients with depression take benzodiazepine drugs long term despite the absence of continuing therapeutic value . AIMS To evaluate a treatment programme involving gradual discontinuation with or without simultaneous selective serotonin reuptake inhibitor ( SSRI ) prescribing and to determine the long-term outcome after benzodiazepine withdrawal . METHOD Patients went through three phases - change to an equivalent dose of diazepam ; subsequent r and omisation to either 20 mg of paroxetine or placebo ; and gradual reduction of diazepam in depression-free patients - with a follow-up after 2 or 3 years . RESULTS A total of 230 patients were recruited and 75 % in the paroxetine group and 61 % in the placebo group were successfully treated after 6 weeks ( P:=0.067 ) . After 2 or 3 years 13 % of patients were still benzodiazepine free : 26 % of those who had successfully tapered off benzodiazepine and 6 % of the total group . CONCLUSIONS Transfer to diazepam followed by gradual withdrawal is an effective way of discontinuing chronic benzodiazepine use . The addition of SSRI treatment is of limited value The Treatment of SSRI-Resistant Depression in Adolescents study ( TORDIA ) was design ed to inform clinicians as to the best next step in the treatment after a depressed adolescent has not responded to an adequate trial with a selective  serotonin re-uptake inhibitor (SSRI).[1 ] In this six-site study , conducted from 2000 to 2006 , 334 treatment-resistant adolescents with major depressive disorder ( MDD ) were r and omized to one of the four treatment strategies in a two-by-two balanced factorial design : ( a ) switch to another SSRI ; ( b ) switch to venlafaxine ; ( c ) switch to another SSRI and add cognitive behavioral therapy ( CBT ) ; or ( d ) switch to venlafaxine and add CBT . The SSRI switch options were fluoxetine , and for the first half of the trial ( n = 181 ) , paroxetine . Because of the concerns about the safety and efficacy of paroxetine , citalopram was used instead during the second half of the trial ( n = 153 ) . All enrolled youth had not responded to an “ adequate trial ” with an SSRI , defined as treatment for at least 8 weeks , with the last 4 weeks at a dosage that was the equivalent of 40 mg of fluoxetine . This communication focuses on acute treatment , which was 12 weeks in duration OBJECTIVE In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression . METHOD Under double-blind conditions , 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks . RESULTS The response rates were 75 % and 46 % for sertraline and paroxetine , respectively . The dropout rate was substantial ( 41 % ) in the paroxetine group and was attributable to side effects . CONCLUSIONS Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression & NA ; The effect of the selective serotonin reuptake inhibitor paroxetine on  diabetic neuropathy symptoms was examined in comparison to imipramine and placebo in a r and omised , double‐blind , cross‐over study . Paroxetine was given as a fixed dose of 40 mg/day , while the dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 400–600 nM. Paroxetine significantly reduced the symptoms of neuropathy as measured by both observer‐ and self‐rating , but was somewhat less effective than imipramine . However , patients showing a weaker response to paroxetine than to imipramine had lower plasma concentrations of paroxetine than patients with similar response to the 2 drugs . On imipramine 5 patients dropped out because of intolerable side effects and 4 of 19 patients completing the study  reported withdrawal symptoms after discontinuing imipramine . On paroxetine no patients dropped out due to side effects and no withdrawal symptoms were reported . Self‐rating showed no depressive symptoms at baseline , and no changes during the study . Neither paroxetine nor imipramine caused changes in objective measures of peripheral nerve function . In conclusion , 40 mg paroxetine/day  significantly reduced the symptoms in peripheral diabetic neuropathy and it was suggested that by dose adjustment on the basis of drug level monitoring , paroxetine may become as effective as imipramine . Paroxetine was devoid of the often disturbing autonomic side effects limiting the use of imipramine in several patients To compare the safety and efficacy of paroxetine ( n= 167 ) and placebo ( n= 169 ) , data from 4 centres using the same protocol were pooled . A double‐blind parallel group design was used , with therapy lasting 6 weeks . Significant differences between  paroxetine‐  and placebo‐treated patients were found on the major efficacy outcome variables by week 2 and on all efficacy variables by week 4 of the study . Improvement on the sleep factor of the Hamilton Rating Scale for Depression was found after 7 d. Observer and patient global efficacy ratings were in agreement by week 4 . No serious adverse events occurred , and paroxetine had no clinical ly significant effects on vital signs or laboratory safety data . Side effects were more common on paroxetine and were similar to other serotonin reuptake inhibitors . In general , these were well tolerated and did not lead to dropout . Symptoms of increased arousal were not seen during early therapy CONTEXT Depression and ischemic heart disease often are comorbid conditions and , in patients who have had a myocardial infa rct ion , the presence of depression is associated with increased mortality . Patients with heart disease need a safe and effective treatment for depression . OBJECTIVE To compare the efficacy , cardiovascular effects , and safety of a specific serotonin reuptake inhibitor , paroxetine , with a tricyclic antidepressant , nortriptyline hydrochloride , in depressed patients with ischemic heart disease . DESIGN Two-week placebo lead-in followed by a double-blind r and omized 6-week medication trial . SETTING Research clinics in 4 university centers . PATIENTS Eighty-one out patients meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease . INTERVENTIONS Treatment with either paroxetine , 20 to 30 mg/d , or nortriptyline targeted to a therapeutic plasma level , 190 to 570 nmol/L ( 50 - 150 ng/mL ) , for 6 weeks . MAIN OUTCOME MEASURES For effectiveness of treatment , a decline in the score of the Hamilton Rating Scale for Depression by 50 % and final score of 8 or less ; for cardiovascular safety , heart rate and rhythm , supine and st and ing systolic and diastolic blood pressures , electrocardiogram conduction intervals , indexes of heart rate variability , and rate of adverse events . RESULTS By intent-to-treat analysis , 25 ( 61 % ) of 41 patients improved during treatment with paroxetine and 22 ( 55 % ) of 40 improved with nortriptyline . Neither drug significantly affected blood pressure or conduction intervals .  Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability , whereas patients treated with nortriptyline had a sustained 11 % increase in heart rate from a mean of 75 to 83 beats per minute ( P<.001 ) and a reduction in heart rate variability , as measured by the SD of all normal R-R intervals over a 24-hour period , from 112 to 96 ( P<.01 ) . Adverse cardiac events occurred in 1 ( 2 % ) of 41 patients treated with paroxetine and 7 ( 18 % ) of 40 patients treated with nortriptyline ( P<.03 ) . CONCLUSIONS Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease .  Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine BACKGROUND The " long/short"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness . We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS ( CDC stages 2B , 2C , 3B , or 3C ) in a 6 week open-label trial with sertraline , paroxetine , or fluoxetine , to assess their effectiveness and tolerability . We further assessed whether treatment of depression result ed in a reduction in both affective and somatic symptoms in this medically ill population . Twenty-four subjects ( 73 % ) completed the trial ( 7 on sertraline , 7 on paroxetine , 10 on fluoxetine ) , 20 ( 83 % ) of whom were clinical responders . Nine dropped out within 1 - 3 weeks of treatment because of adverse effects , mostly agitation , anxiety , and insomnia . Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms , many of the latter having been attributed to HIV rather than depression . These results suggest that , even in later stages of HIV illness , the contribution of depression to perceived somatic symptoms may be significant , and that these symptoms may improve with antidepressant treatment Genetic variation at the FKBP5 locus has been reported to affect clinical outcomes in patients treated with antidepressant medications  in several studies . However , other reports have not confirmed this association . FKBP5 may regulate the sensitivity of the hypothalamic – pituitary – adrenal axis . We tested two  FKBP5 single nucleotide polymorphisms ( rs1360780 and rs3800373 ) in a sample of 246 geriatric patients treated for 8 weeks in a double‐blind r and omized comparison trial of paroxetine and mirtazapine .  These two polymorphisms had previously been reported to predict efficacy in depressed patients treated with selective serotonin reuptake inhibitors such as paroxetine , and those treated with mirtazapine , an agent with both serotonergic and noradrenergic actions . However , we found no significant associations between these FKBP5 genetic variants and clinical outcomes . Neither mean Hamilton Depression Rating Scale scores nor time to remission or response were predicted by FKBP5 genetic variation . These results suggest that FKBP5 is unlikely to play a major role in determining antidepressant treatment outcomes in geriatric patients . © 2009 Wiley‐Liss , & NA ; The abrupt discontinuation of antidepressants can result in a syndrome of adverse events , including somatic , mood and psychomotor reactions . This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors ( SSRIs ) on cognitive and psychomotor function . Eighty‐seven patients receiving maintenance therapy with fluoxetine , sertraline , paroxetine or citalopram had their treatment interrupted for 4‐7 days using double‐blind placebo . Assessment s of aspects of cognitive and psychomotor performance , mood and symptoms were carried out at each visit . Following interruption of treatment , significant differences between the groups emerged . Paroxetine treated patients experienced significantly more cognitive failures ( P = 0.007 ) , poorer quality of sleep ( P = 0.016 ) , and an increase in depressive symptoms , as rated both subjectively , using the Zung scale ( P = 0.006 ) and by the clinician , using the Montgomery‐Asberg Depression Rating Scale ( P = 0.0003 ) and Clinical Global Impression ( P = 0.0003 ) , compared to some or all of the other drugs . All changes were reversed on reinstatement of treatment . Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning , which may be related to the antidepressant discontinuation syndrome . These effects are not evident in patients receiving fluoxetine , sertraline and citalopram , suggesting they are not an SSRI class phenomenon . Int Clin Psychopharmacol 15:305‐318 © 2000 Lippincott Williams & BACKGROUND Generalized social anxiety disorder ( GSAD ) is a pervasive form of social anxiety that affects approximately 5 % of persons in the community . Among evidence -based pharmacologic treatments for the disorder , selective serotonin reuptake inhibitors ( SSRIs ) have become widely used and are known to be efficacious . Monotherapy with the benzodiazepine clonazepam is also efficacious for GSAD , but the adjunctive use of clonazepam with an SSRI to potentially improve outcomes has not been studied to date . METHOD Twenty-eight patients ( 22 men and 6 women ) with DSM-IV-defined GSAD were r and omly assigned to receive double-blind clonazepam ( or placebo ) , 1.0 to 2.0 mg/day ( divided b.i.d . ) along with open-label paroxetine , 20 to 40 mg/day , for 10 weeks . A 2-week taper of double-blind medication was followed by an additional 8 weeks of open-label paroxetine treatment ( during which the dose of paroxetine could be increased to a maximum of 50 mg/day ) . Twenty-three patients ( 82 % ) met DSM-IV criteria for avoidant personality disorder . The patients ' mean + /- SD age was 31.2 + /- 7.7 years , and their mean duration of illness was 12.1 + /- 5.8 years . Data were gathered from August 2001 to April 2002 . RESULTS Nineteen ( 68 % ) of 28 patients completed treatment . At the end of the 10-week double-blind treatment , there was a trend ( p < .06 ) favoring the paroxetine/clonazepam group , who had a 79 % response rate ( Clinical Global Impressions-Global Improvement scale [ CGI-I ] score of 1 or 2 ) compared with a 43 % response rate for the paroxetine/placebo group . However , no significant differences on other outcome measures were noted between the 2 groups in an intent-to-treat analysis , in terms of either very early ( 2 - 4 weeks ) or not as early ( 5 - 10 weeks ) responses during treatment . Dropout rates due to adverse events were rare ( 1 patient in each group ) , indicating that the paroxetine/clonazepam combination was well tolerated . CONCLUSION Coadministration of clonazepam with an SSRI , in contrast to findings in panic disorder , did not lead to more rapid resolution of symptoms in GSAD . On the other h and , there is some evidence that the clonazepam-added group had superior global outcomes ( e.g. , as measured on the CGI-I ) , although power to detect such differences in this study was small . These observations suggest that a role for adjunctive benzodiazepines in patients with GSAD ( e.g. , for augmenting SSRI partial response or nonresponse ) is deserving of further controlled investigation Abstract . Rationale : The DSM-IV includes the specifier " generalized " to refer to social anxiety disorder ( social phobia ) patients if the fears include " most social situations " . The focus on interventions such as the selective serotonin reuptake inhibitors ( SSRIs ) for generalized social anxiety disorder arguably runs the risk that inadequate treatment will be provided to patients with the non-generalized or discrete subtypes . There are , however , few data to address whether more generalized and less generalized subgroups of social anxiety disorder differ in response to medication . Objective : To compare response of more generalized and less generalized social anxiety disorder to pharmacotherapy . Methods : Data from three r and omized placebo-controlled double-blind multicenter trials of the SSRI paroxetine in social anxiety disorder were pooled . Response on the Clinical Global Impression Global Improvement item was analyzed using logistic regression , and change in total Liebowitz Social Anxiety Score was analyzed using analysis of variance , with both models incorporating treatment ( paroxetine vs placebo ) , subgroup ( more generalized vs less generalized ) , demographic , and clinical variables . Results : The prevalence of more generalized social anxiety disorder was higher in females than in males . However , there was no significant difference in terms of age or clinical characteristics ( duration of condition , baseline pulse , mean arterial blood pressure ) . At treatment endpoint there were significant treatment effects ( for paroxetine vs placebo ) , but no significant subgroup effects ( for more generalized vs less generalized ) . Conclusions : Although the current data base is limited insofar as few patients with discrete social anxiety disorder would have been included , it is helpful in addressing the value of medication for patients lying on the spectrum from generalized to non-generalized and discrete social anxiety disorder .  Paroxetine was effective in both more generalized and in less generalized social anxiety disorder To evaluate the possible influence of buspirone on sexual dysfunction in depressed patients treated with a selective serotonin reuptake inhibitor ( SSRI )  , we analyzed data from a placebo-controlled trial design ed to explore the efficacy of buspirone as add-on treatment for patients not responding to an SSRI alone . At baseline , all patients met the criteria for a major depressive episode according to DSM-IV and had received citalopram or paroxetine during a minimum of 4 weeks without responding to the treatment .  Buspirone ( flexible dosage , 20 - 60 mg/day ) or placebo was added to the SSRI for 4 weeks ; the mean daily dose of buspirone at endpoint was 48.5 mg ( SD = 1.0 ) . Sexual dysfunction was evaluated using a structured interview . Before starting medication with buspirone or placebo , 40 % ( 47 of 117 ) reported at least one kind of sexual dysfunction ( decreased libido , ejaculatory dysfunction , orgasmic dysfunction ) . During the 4 weeks of treatment , approximately 58 % of subjects treated with buspirone reported an improvement with respect to sexual function ; in the placebo group , the response rate was 30 % . The difference between placebo and active drug treatment was more pronounced in women than in men . The response was obvious during the first week , with no further improvement during the course of the study . It is suggested that the effect of buspirone on sexual dysfunction is a result of a reversal of SSRI-induced sexual side effects rather than of an antidepressant effect of the drug BACKGROUND Approximately half of patients who are prescribed selective serotonin re-uptake inhibitors ( SSRIs ) either do not respond to treatment or do not experience a sustained response . OBJECTIVE The purpose of this study was to assess the efficacy of venlafaxine immediate-release ( IR ) and extended-release ( XR ) in out patients who either did not respond to SSRI treatment or did not maintain a sustained response . METHODS Out patients who met the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria for major depressive disorder who were previously treated with an SSRI ( fluoxetine > or = 20 mg/d ; sertraline > or = 50 mg/d ; paroxetine > or = 20 mg/d ) for > or = 6 weeks , but demonstrated an inadequate or unsustained response , were switched  to venlafaxine ( IR or XR formulation , 50 - 400 mg/d , titrated from 37.5 mg/d ) for > or = 6 weeks . Response at 6 to 8 weeks was defined as total score < or = 10 on the modified 25-item Hamilton Depression ( HAM-D25 ) rating scale or total score > or = 5 on the 21-item Patient Global Improvement ( PGI-21 ) scale . Remission was defined as a HAM-D25 total score < or = 8 or PGI-21 score > or = 7 . Tests were administered by an unblinded , board-certified psychiatrist . RESULTS A total of 73 patients ( 54 women , 19 men ; mean age , 38.6 years ) were enrolled and treated with venlafaxine IR ( n = 63 ) or venlafaxine XR ( n = 10 ) ; 33 were SSRI nonresponders and 36 had an unsustained response to SSRI treatment . Four patients receiving venlafaxine IR discontinued due to drug-related adverse events ( agitation , sedation , or nausea ) . Data from these patients were excluded from the analysis . After 6 to 8 weeks of treatment , 94.2 % ( 65/69 ) of patients were considered responders ( HAM-D25 or PGI-21 criteria ) ; 91.3 % ( 63/69 ) of patients responded to treatment as assessed by both measures . Eighty-seven percent ( 60/69 ) and 85.5 % ( 59/69 ) of patients achieved remission based on HAM-D,5 and PGI-21 criteria , respectively . Response/remission rates were comparable among patients treated with SSRIs , regardless of whether patients had failed to respond to treatment with 1 or 2 SSRIs . CONCLUSION Venlafaxine IR/venlafaxine XR may be effective in out patients with major depressive disorder who do not respond or have an unsustained response to SSRIs . However , r and omized , controlled trials are needed before any conclusions can be drawn about the efficacy of this agent in this population OBJECTIVE To determine the relative cost-effectiveness of three classes of antidepressants : tricyclic antidepressants ( TCAs ) , selective serotonin reuptake inhibitors ( SSRIs ) , and the modified TCA lofepramine , as first choice treatments for depression in primary care . DESIGN Open , pragmatic , controlled trial with three r and omised arms and one preference arm . Patients were followed up for 12 months . SETTING UK primary care : 73 practice s in urban and rural areas in Engl and . PARTICIPANTS Patients with a new episode of depressive illness according to GP diagnosis . INTERVENTIONS Patients were r and omised to receive a TCA ( amitriptyline , dothiepin or imipramine ) , an SSRI ( fluoxetine , sertraline or paroxetine ) or lofepramine . Patients or GPs were able to choose an alternative treatment if preferred . MAIN OUTCOME MEASURES At baseline the Clinical Interview Schedule , Revised ( CIS-R PROQSY computerised version ) was administered to establish symptom profiles . Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression ( HAD-D ) , CIS-R , EuroQol ( EQ-5D ) for quality of life , Short Form ( SF-36 ) for generic health status , and patient and practice records of use of health and social services . The primary effectiveness outcome was the number of depression-free weeks ( HAD-D less than 8 , with interpolation of intervening values ) and the primary cost outcome total direct NHS costs . Quality -adjusted life-years ( QALYs ) were used as the outcome measure in a secondary analysis . Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed . Estimates were bootstrapped with 5000 replications . RESULTS In total , 327 patients were r and omised . Follow-up rates were 68 % at 3 months and 52 % at 1 year . Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients r and omised to TCAs entered the preference arm than those allocated to the other choices . Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm . There were no significant differences between arms in mean cost per depression-free week . For values placed on an additional QALY of over 5000 pounds , treatment with SSRIs was likely to be the most cost-effective strategy .  TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively , but these differences were relatively modest . CONCLUSIONS When comparing the different treatment options , no significant differences were found in outcomes or costs within the sample , but when outcomes and costs were analysed together , the result ing cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option , although the probability of this did not rise above 0.6 . Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks . Further research is still needed on the management of depressive illness in primary care . This should address areas such as the optimum severity threshold at which medication should be used ; the feasibility and effectiveness of adopting structured depression management programmes in the UK context ; the importance of factors such as physical co-morbidity and recent life events in GPs ' prescribing decisions ; alternative ways of collecting data ; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early This study was aim ed at resolving the time course of clinical action of antidepressants ( ADs ) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients . The first goal was to identify , during the first 2 weeks of treatment , the onset of clinical actions of the selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , and the selective noradrenergic reuptake inhibitor , desipramine ( DMI ) . The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients . The design was a r and omized , parallel group , placebo-controlled , double-blind study for 6 weeks of treatment following a 1-week washout period . The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity . The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days , averaged 13 days for paroxetine , and was 16–42 days for placebo . Furthermore , as hypothesized , the different types of ADs initially impacted different behavioral aspects of the disorder . After 1 week of treatment , DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo , and this difference persisted at the second week of treatment . Early improvement in depressed mood – motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not . Paroxetine initially reduced anxiety more in responders than in nonresponders , and by the second week , significantly improved depressed mood and distressed expression in responders to a greater extent . Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement . Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs , results that could eventually be applied directly to clinical practice Dose escalation is often used in depressed patients who fail to respond to st and ard doses of selective serotonin reuptake inhibitors , but clinical efficacy is equivocal . We aim ed to reassess the efficacy of paroxetine dose escalation and quantify whether paroxetine dose escalation increases occupancy of the serotonin transporter ( SERT ) more than placebo dose escalation in a r and omized controlled trial . We recruited 107 nonpsychotic , unipolar depressed out patients ( 18 - 70 years ; Hamilton Depression Rating Scale ( HDRS(17 ) ) > 18 ) from primary care and psychiatric outpatient departments . After 6 weeks , open-label paroxetine 20 mg per day ( T0 ) , nonresponding patients ( HDRS(17 ) decrease < 50 % ; n=60 ) were r and omized to double-blind paroxetine ( 30 - 50 mg per day as tolerable ) or placebo dose escalation ( paroxetine 20 mg per day+placebo ) . Patients were followed until 6 weeks after r and omization ( T1 ) . Forty-nine patients , drug free at study entry , underwent single-photon emission-computed tomography ( SPECT ) scanning before treatment and were scanned repeatedly at T0 and T1 .  Paroxetine serum concentrations and SERT occupancy were determined at T0 and T1 ( n=32 ) . We terminated the dose-escalation trial after an interim analysis . Thirty nonresponding patients were r and omized to paroxetine ( 46.7+/-5.5 mg per day ) , 27 to placebo dose escalation . Response rates were 10/30 ( 33.3 % ) and 10/27 ( 37.0 % ) , respectively . Repeated measurement analyses showed no significant effect for treatment ( p=0.88 , exceeding a priori stopping rules for futility ( p>0.5 ) ) . Overall dropout was higher for placebo ( 26.7 % ) than paroxetine ( 3.3 % ; p=0.03 ) . Paroxetine dose escalation increased  paroxetine serum concentrations ( p<0.001 ) . SPECT measurements ( 12 patients r and omized to paroxetine ( 46.9+/-4.8 mg ) and 14 to placebo dose escalation ) showed no significant increase of midbrain SERT occupancy ( 2.5+/-26.4 % , paroxetine ; 3.1+/-25.8 % placebo ; p=0.687 ) nor in diencephalon ( p=0.529 ) . Paroxetine dose escalation in depressed patients has no clinical benefit over placebo dose escalation . This is explained by the absence of significant increases of SERT occupancy by paroxetine dose escalation , despite increased paroxetine serum concentrations ( IS RCT N44111488 ) This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents . Adolescents ( n = 334 ) with major depression who had not responded to a selective serotonin reuptake inhibitor ( SSRI )  were r and omized to 1 of 4 treatments : switch to another SSRI ( fluoxetine , citalopram , or paroxetine ) , switch to venlafaxine , switch to SSRI plus cognitive behavior therapy , or switch to venlafaxine plus cognitive behavior therapy . Adolescents who did not improve by 6 weeks had their dose increased . Plasma concentrations of medication and metabolites were measured at 6 weeks in 244 participants and at 12 weeks in 204 participants . Adolescents treated with citalopram whose plasma concentration was equal to or greater than the geometric mean ( GM ) showed a higher response rate compared to those with less than the GM , with parallel but nonsignificant findings for fluoxetine . A dose increase of citalopram or fluoxetine at week 6 was most likely to result in response when it led to a change in concentration from less than the GM at 6 weeks to the GM or greater at week 12 . Plasma levels of paroxetine , venlafaxine , or O-desmethylvenlafaxine were not related to clinical response . Exposure was associated with more cardiovascular and dermatologic side effects in those receiving venlafaxine . Antidepressant concentration may be useful in optimizing treatment for depressed adolescents receiving fluoxetine or citalopram Paroxetine ( 30 mg ) , a selective serotonin ( 5-HT ) reuptake inhibitor , was compared in a double-blind trial to amitriptyline ( 150 mg ) in a sample of 40 in patients aged 18 - 65 years who fulfilled Research Diagnostic Criteria for major depression . Patients were studied after a placebo drug washout period of 10 days and after an active 4-week treatment period . Sleep EEG recordings were performed before and at the end of the study as well as during acute treatment ( first 2 days ) and following withdrawal of active medication . Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile typical of 5-HT reuptake inhibition . Paroxetine and amitriptyline decreased the amount of REM sleep , a well-known effect of classical antidepressants . Paroxetine also shared with other 5-HT reuptake inhibitors an alerting effect on sleep that was not shown to be detrimental on subjective sleep quality OBJECTIVE To compare the efficacy and tolerability of paroxetine ( a selective serotonin reuptake inhibitor ) with that of amitriptyline ( a tricyclic antidepressant ) in the treatment of depression in 191 patients with rheumatoid arthritis ( RA ) . METHODS A r and omized , double blind , double dummy , parallel group study . A placebo washout period of 3 - 7 days was followed by an 8 week active treatment phase during which patients received either paroxetine ( 20 - 40 mg daily ) or amitriptyline ( 75 - 150 mg daily ) . The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint . RESULTS Paroxetine was as effective as amitriptyline for the treatment of depression , with similar improvements in RA associated pain and disability also seen in both groups . However , paroxetine was better tolerated than amitriptyline , with an overall frequency of adverse experiences of 56.4 % and 67.7 % in the 2 groups , respectively . The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group ( 18.1 % vs 43.8 % taking amitriptyline ) and paroxetine treated patients also experienced fewer severe ( 16.0 % vs 21.9 % ) , serious nonfatal ( 0 % vs 4.2 % ) , and drug related adverse experiences ( 12.8 % vs 29.2 % ) . CONCLUSION Tolerability is an important consideration in this patient population , which is largely composed of elderly patients who are taking additional medications for RA .  Paroxetine shows a number of advantages in the management of depression comorbid with RA A r and omized , double‐blind , parallel‐group , 6‐week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine . After a 1‐week placebo wash‐out , patients suffering from DSM‐III major depression and with a score of 18 or more on the 21‐item Hamilton Rating Scale for Depression ( HRSD ) received either paroxetine or fluoxetine . The patients were assessed for efficacy using the HRSD , Montgomery‐Åsberg Depression Rating Scale and Clinical Global Impression ; for tolerability , adverse events were elicited by the use of a non‐leading question and a side effects checklist . The groups of patients were comparable on entry to the study . One hundred patients were recruited into the study , of whom 78 were evaluable for the efficacy analysis .  Paroxetine and fluoxetine showed comparable efficacy at the end of the 6‐week treatment period , but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed . This could suggest an earlier onset of action with paroxetine .  Also , associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3 . Patients on paroxetine reported fewer adverse events than those on fluoxetine . The most commonly reported adverse events were nausea and vomiting in both groups The relationship of the serotonin transporter gene promoter region polymorphism ( 5-HTTLPR ) to antidepressant response was examined in 95 elderly patients receiving a protocol ized treatment for depression with paroxetine or nortriptyline .  Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations . Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele . There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression ( HRSD ) scores or anxiety symptoms . During acute treatment with paroxetine , mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele , despite equivalent paroxetine concentrations . Onset of response to  nortriptyline  was not affected . Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor Depressive illness among the elderly is an important public health concern . However , treatment of the elderly may be complicated by age-related changes in physiology , general medical status , and susceptibility to side effects . There is therefore a need for improved treatment modalities for depressed elderly patients .  Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake . It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants . The authors present the combined data from two similarly design ed comparisons of paroxetine and doxepin in out patients over 60 years of age with major depression . The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression ( HAM-D ) total score , the Montgomery and Asberg Depression Rating Scale ( MADRS ) , and the Hopkins Symptom Checklist ( SCL ) depression factor score .  Paroxetine was significantly superior to doxepin on the Clinical Global Impressions ( CGI ) scale for severity of illness , the HAM-D retardation factor , and the HAM-D depressed mood item .  Doxepin produced significantly more anticholinergic effects , sedation , and confusion . Paroxetine was associated with more reports of nausea and headache . These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly Abrupt onset of hot flashes poses a significant problem for women treated with chemotherapy for breast cancer . Alternatives to hormone replacement , such as the use of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine hydrochloride , are being explored as therapies for hot flashes in this patient population . The present study investigated the efficacy of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer . This study included 13 patients who were seen in the Psychosocial Clinic at Moffitt Cancer Center . They were referred by their medical oncologist after reporting complaints of significant difficulty with hot flashes . Baseline question naires were completed and a structured diagnostic interview for clinical depression was conducted , all of which were repeated 5 weeks after the paroxetine 20 mg daily was started . Significant improvements were seen in the ratings of hot flash severity ( P = 0.002 ) . In addition , significant improvements were observed in general , emotional , and mental fatigue . Rates of clinical ly significant depressive symptomatology also decreased and sleep quality improved significantly as well . Finally , the incidence of clinical depression improved from 39 % at baseline to 8 % after treatment . These preliminary data suggest that the antidepressant paroxetine can be helpful in the treatment of hot flashes and associated fatigue , sleep disturbance , and depression in women with breast cancer treated with chemotherapy . Further controlled studies are needed to more fully evaluate the efficacy of the SSRIs for hot flashes in women with breast cancer Objective : The alpha 2A-adrenergic receptor ( ADRA2A ) plays a central role in the regulation of systemic sympathetic activity . Recently , the functional defect of ADRA2A has been implicated as a cause of depression , attention deficit hyperactivity disorder , and Tourette syndrome . In this study , the effect of genetic variants of the ADRA2A gene on the response to selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors ( SNRIs ) was examined in depressed patients . Method : Ninety-three Japanese depressed patients were recruited in the present study , assigned r and omly to paroxetine or milnacipran , and assessed by the Hamilton Rating Scale for Depression ( HAM-D ) scoring every 2 weeks before and after drug administration . The ADRA2A C-1297 G polymorphism was considered in the association analysis with the efficacy of antidepressants . Results : There were significant differences in the HAM-D percent score change over time ( P = 0.019 ) among C/C , C/G , and G/G of the ADRA2A C-1297 G polymorphism in the total subjects . The C allele carriers of the ADRA2A C-1297 G polymorphism showed a significantly better improvement than G/G subjects at weeks 2 , 4 , and over time ( P = 0.037 ) in the milnacipran group . Discussion : Our findings suggest that ADRA2A plays an important role in depression therapy . The level of ADRA2A expression could be associated with the efficacy of SSRIs/SNRIs , especially milnacipran , although the functional change brought about by C-1297 G polymorphism has not yet been fully identified in vivo and in vitro . Conclusions : The ADRA2A polymorphism could be a reasonable c and i date to predict the response to milnacipran . Our results are still preliminary , and a large sample size will be required to confirm our findings . However , to the best of our knowledge , this study is the first to suggest a possible association of ADRA2A variants with the SNRI response BACKGROUND Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors . In a 12-week r and omized , multicenter , double-blind trial , the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression . METHODS A total of 203 patients were r and omized to fixed doses ( 20 mg/day ) of paroxetine or fluoxetine for the first six weeks of therapy . From week 7 - 12 , dosing could be adjusted biweekly , as required ( paroxetine 20 - 50 mg/day , and fluoxetine 20 - 80 mg/day ) . The mean prescribed doses were paroxetine 25.5 mg/day ( range 20.0 - 40.2 mg/day ) , and fluoxetine 27.5 mg/day ( range 20.0 - 59.5 mg/day ) . Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia . RESULTS Both active treatments demonstrated comparable antidepressant efficacy ( HAM-D , CGI ) . Anxiolytic activity of the two drugs ( COVI , STAI , HAM-D ) was also comparable . However , paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy ( HAM-D Agitation item , p < 0.05 ; Psychic Anxiety item , p < 0.05 ) , with no differences detected after week 2 . The overall incidence of adverse effects was comparable in the two treatment groups . Constipation , dyspepsia , tremor , sweating and abnormal ejaculation were more common in paroxetine-treated subjects , whereas nausea and nervousness were more frequent in fluoxetine-treated patients . Weight loss was more common in the fluoxetine versus paroxetine group ( 11.88 % versus 2.94 % , respectively ) . ESRS scores for akathisia were low throughout the study and showed little change . LIMITATIONS Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others . DISCUSSION The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy .  Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine Paroxetine is a selective serotonin reuptake inhibitor which is being developed as an antidepressant . Previous studies suggest it is effective in the treatment of depression and has a low incidence of side effects . The authors report on a 6-week , r and omized , prospect i ve trial of paroxetine , imipramine , and placebo in 120 out patients with major depression . The results showed that paroxetine was significantly superior to placebo in relieving depression . There were no significant differences in antidepressant efficacy between paroxetine and imipramine . However , paroxetine was also significantly superior to placebo on several measures of anxiety . Imipramine either was not superior on these measures or took longer to show a significant difference . Paroxetine lacked the typical anticholinergic side effects that accompanied imipramine therapy . The results show that paroxetine is an effective antidepressant that may have value especially when depression is accompanied by significant anxiety Objective To assess the potential economic impact of new and more expensive antidepressants on the overall cost of treatment using cost-effectiveness analysis . Method For this analysis , a computerized decision tree of clinical practice was developed to model the 12-month treatment of moderate to severe depression in Canada . To complete the model , data were obtained from physician panels , the Ontario Ministry of Health , and clinical comparative trials of paroxetine , a selective serotonin reuptake inhibitor , and Imipramine , a tricyclic antidepressant . Results The overall cost of treatment when paroxetine 30 mg per day was used first-line was found to be lower than when generic imipramine was used as the initial therapy ( $ 1697 versus $ 1793 ) . The higher drug cost of paroxetine ( $ 1.69 per day ) versus imipramine ( $ 0.05 per day ) was offset by a higher rate of treatment failures with the tricyclic necessitating an alternate therapy , additional physician visits and /or hospitalization . Sensitivity analysis of key variables determined that drug price and relapse rates after discontinuation were relatively insensitive predictors of the overall cost of care . More important was the continuation rate while on different therapies . Conclusion Paroxetine demonstrated a cost-benefit relative to Imipramine when the continuation rate was ≥ 47 % . Clinical trials of paroxetine have reported continuation rates of 41 % to 65 % , suggesting that paroxetine is a cost-effective alternative to Imipramine in the 1-year management of patients with moderate to severe depression Paroxetine , a phenylpiperidine derivative , is an antidepressant that selectively inhibits serotonin reuptake . In this study 111 out patients with major depression diagnosed by DSM-III criteria were treated with either paroxetine or placebo in a 6-week , r and omized , double-blind study . Paroxetine was significantly superior to placebo on six of the seven major efficacy variables . Significant differences in favor of paroxetine were apparent by Week 2 . Paroxetine was also well tolerated . These results support the efficacy and safety of paroxetine as a treatment for patients with major depression Paroxetine is an investigational antidepressant that acts through selective inhibition of serotonin reuptake at the synapse . In this study , 81 out patients with major depression according to DSM-III criteria were treated with either paroxetine or placebo in a 6-week , r and omized , double-blind study . Paroxetine was significantly superior to placebo on all major efficacy variables , including depression as well as anxiety , cognitive disturbance , insomnia , psychomotor retardation , and sleep disturbance . Significant differences in favor of paroxetine were apparent by Week 2 . Paroxetine was also well tolerated . The results support the efficacy and safety of paroxetine as a treatment for patients with major depression Paroxetine is a selective serotonin uptake inhibitor , which is being investigated as an antidepressant . In this double‐blind , six‐week study 120 out patients with DSM‐I11 major depression were r and omly assigned to treatment with paroxetine , imipramine , or placebo . Results showed a statistically significant superiority of paroxetineover placebo on almost all outcome measures . Paroxetine was significantly superior to imipramine on the HAMD total score and was generally better tolerated than imipramine . The results support paroxetine 's effectiveness in the treatment of major depression and suggest that further studies with this compound are warranted Purpose : Hot flash ( HF ) is a common side effect in prostate cancer patient undergoing and rogen-deprivation therapy ( ADT ) . In this study , we evaluated the efficacy of paroxetine ( selective serotonin reuptake inhibitors ( SSRIs ) ) for HF . Patients and methods : In total , 10 men with prostate cancer under ADH who were suffering with HF entered this study . Self-report question naire was used for the evaluation . Results : The average rating for HF frequency decreased ( P=0.009 ) and HF severity decreased ( P=0.0332 ) also , reported QOL score increased ( P=0.0218 ) . Conclusion : These preliminary data suggest that low dose ( 10 mg/day ) of antidepressant paroxetine can be helpful in the treatment of HFs in patients under ADT for prostate cancer . Further controlled studies are needed to more fully evaluate the efficacy of the SSRIs Objective : To assess the efficacy of a selective serotonin reuptake inhibitor ( paroxetine ) for relief of tinnitus . Design : One hundred twenty tinnitus sufferers participated in a r and omized double-blind placebo-controlled trial . Paroxetine or placebo was increased to a maximally tolerated dose ( up to 50 mg/day ) , and patients were treated for a total of 31 days at the maximal dose . Methods : Patients with chronic tinnitus were recruited from our university-based specialty clinic by referral from otolaryngologists and audiologists in the local community and by advertisement . Patients with psychotic or substance use disorders or suicidal ideation were excluded , as were those using psychoactive medications  ( this result ed in only 1 subject with major depression in the study ) or any other medications that interact with paroxetine and those with inability to hear at one ’s tinnitus sensation level . Fifty-eight percent of patients were male , 92 % were Caucasian , and the average age was 57 . Outcomes Measures : Tinnitus matching , the Tinnitus H and icap Question naire , the question : How severe ( bothered , aggravating ) is your tinnitus ? Quality of Well-Being and other psychological question naires . Results : Paroxetine was not statistically superior to placebo on the following tinnitus measures ( tinnitus matching , 5- or 10-db drop , Tinnitus H and icap Question naire , quality of well-being measures , how severe , how bothered , positive change ) . There was a significant improvement in the single item question , How aggravating is your tinnitus ? for those in the paroxetine group compared with the placebo group . Conclusions : These results suggest that the majority of individuals in this study did not benefit from paroxetine in a consistent fashion . Further work remains to be done to determine if subgroups of patients ( e.g. , those who tolerate higher doses , those who are depressed ) may benefit . UCSD = University of California , San Diego Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors . The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine . However , most data were collected in sample s of out patients . To overcome this restriction , a six-week double-blind control-group study , comparing 30 mg paroxetine with 150 mg amitriptyline per day , was performed in a sample of in patients suffering from major depression . Generally speaking , the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline , either with respect to the total score on the Hamilton Depression Scale ( HAMD ) and the Clinical Global Impressions or with respect to the subscores of the HAMD . One exception was the retardation subscore , in which amitriptyline showed a greater degree of reduction . Both drugs had a characteristic side-effect profile .  Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea Considerable research shows that serotonin dysfunction is implicated in major depression .  Paroxetine is an investigational antidepressant that appears to act by selectively blocking neuronal serotonin uptake . Seventy-two out patients with moderate-to-severe major depression entered this 6-week , double-blind comparison of paroxetine and placebo . The results showed clear and significant superiority of paroxetine on all of the major outcome variables . These included physician-rated measures such as the Hamilton Rating Scale for Depression and its four factor scores , the Clinical Global Impressions scale , the Montgomery and Asberg Depression Rating Scale , and the Raskin Depression Scale . Results on these agreed well with patient-rated measures like the Hopkins Symptom Checklist and Patient Global Evaluation Scale .  Paroxetine was also very well tolerated . Nausea and constipation occurred significantly more often with paroxetine , but only 9 % of paroxetine patients dropped out of the study due either in whole or in part to an adverse effect . This compares to 8 % of the placebo patients who were discontinued for the same reason . This study suggests that paroxetine is a safe and effective medication for the treatment of major depression Summary Background . Fatigue can significantly interfere with a cancer patient ’s ability to fulfill daily responsibilities and enjoy life . It commonly co-exists with depression in patients undergoing chemotherapy , suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue . Methods . We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy r and omly assigned to receive either  20 mg of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine ( Paxil ® , SmithKline Beecham Pharmaceuticals ) or an identical-appearing placebo . Patients began their study medication seven days following their first on- study treatment and continued until seven days following their fourth on- study treatment . Seven days after each treatment , participants completed question naires measuring fatigue ( Multidimensional Assessment of Fatigue , Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist ) and depression ( Profile of Mood States-Depression subscale [ POMS-DD ] and Center for Epidemiologic Studies -Depression [ CES-D ] ) . Results . Repeated- measures ANOVAs , after controlling for baseline measures , showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D ( p=0.006 ) and the POMS-DD ( p=0.07 ) but not in reducing fatigue ( all measures , ps > 0.27 ) . Conclusions . Although depression was significantly reduced in the 44 patients receiving paroxetine  compared to the 50 patients receiving placebo , indicating that a biologically active dose was used , no significant differences between groups on any of the measures of fatigued were observed . Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment The phenylpiperidine derivative paroxetine is a selective serotonin reuptake inhibitor . In a double-blind 6-week trial , paroxetine was compared with amitriptyline in hospitalized patients suffering from major depression ( DSM-III ) . One hundred fifty-three patients were enrolled in the study in seven centers in Austria and Germany . Results showed similar efficacy of both drugs after 6 weeks . The differences between groups in Mont-gomery-Asberg Depression Rating Scale and Clinical Global Impression ratings did not reach statistical significance at any time . Side effects were distributed similarly but with a significantly higher incidence of anticholinergic effects in patients treated with amitriptyline ( p < 0.001 ) , whereas agitation and insomnia were registered more often in the paroxetine group . This study supports the antidepressive efficacy of paroxetine in a sample of severely depressed in patients In view of the fact that controlled prospect i ve studies on the benefits of dose escalation of the selective serotonin re‐uptake inhibitor ( SSRI ) paroxetine are lacking , we conducted a double‐blind , r and omized , parallel‐group multicentre study design ed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria ( RDC ) with inadequate treatment response . The study sample consisted of 544 out‐ patients with different degrees of severity of depression . Patients received either 20 mg paroxetine ( n=271 ) or 100 mg maprotiline ( n=273 ) for the first 3 weeks in a double‐blind manner . Response after 3 weeks was defined using explicit operationalized criteria . Patients with inadequate treatment response ( paroxetine group , n=86 ; maprotiline group , n=88 ) were again r and omized to either continuation of the previous dosage ( paroxetine , n=36 ; maprotiline , n=48 ) or increased doses , i.e. 40 mg paroxetine ( n=50 ) or 150 mg maprotiline ( n=40 ) , respectively . Intention‐to‐treat and completer analyses were performed . Defining response as a reduction in Hamilton Depression Rating Scale ( 17‐item version ) ( HAMD‐17 ) score of at least 50 % from baseline , no significant benefits of dose escalation were found for either paroxetine or maprotiline . Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation . After dose escalation , new adverse events that had not been present during treatment with lower doses rarely occurred . Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients BACKGROUND Depression is frequently observed in patients with heart failure and is associated with poor quality of life and adverse prognosis . However , the prevalence of depression in heart failure could be overestimated because symptoms of depression overlap with those of heart failure . Similarly , the importance of depression may be overestimated if depression merely reflects worse heart failure . Because the response to depression treatment has not been evaluated in this patient population , we evaluated the efficacy of controlled-release paroxetine ( paroxetine CR ) , a selective serotonin reuptake inhibitor , on depression and quality of life in chronic heart failure . METHODS A double-blind , r and omized , placebo-controlled design was used to evaluate reductions in depression following 12 weeks of treatment with paroxetine CR ( n = 14 , age 62.1 + /- 12.3 years ) or placebo ( n = 14 , age = 61.9 + /- 9.0 years ) . Patients with symptomatic congestive heart failure and a score of at least 10 on the Beck Depression Inventory ( BDI ) were eligible .  Beck Depression Inventory was obtained at baseline and 4 , 8 , and 12 weeks of follow-up . Quality of life was assessed using the Medical Outcomes Study Short Form and the Minnesota Living with Heart Failure Question naire . RESULTS Controlled-release paroxetine result ed in significantly more recovery from depression ( BDI < 10 ) than placebo ( 69 % vs 23 % , P = .018 ) and result ed in lower continuous BDI scores throughout the intervention ( P = .024 ) . Controlled-release paroxetine was associated with higher general health levels compared with placebo on the Medical Outcomes Study 36-Item Short Form survey ( 38 + /- 10 vs 30 + /- 6 , P = .016 ) at 12 weeks of follow-up . Reductions in depression were correlated with improvements in psychological aspects of quality of life ( P < .05 ) but not with physical quality of life measures ( P > .10 ) . CONCLUSION Antidepressant therapy with paroxetine CR results in significant reductions in depression among patients with heart failure . The reductions in depression with paroxetine CR are accompanied by improvements in psychological aspects of quality of life . Larger controlled trials are needed to further document the effectiveness of paroxetine CR and other selective serotonin reuptake inhibitors in patients with heart failure and to determine patient subgroups that are most likely to benefit from antidepressive interventions BACKGROUND Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness , insomnia , nervousness , nausea , and agitation . We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment , based on fluoxetine 's longer half-life . METHODS In this 4-week study , 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine , sertraline , or paroxetine for 4 - 24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5 - 8 days . The  Symptom Question naire ( SQ ) , the Discontinuation-Emergent Signs and Symptoms checklist , the 28-item Hamilton Depression Rating Scale , and the Montgomery-Asberg Depression Rating Scale  were used to assess somatic distress and stability of antidepressant response . RESULTS Two hundred twenty patients ( 91 % ) completed the study . Following interruption of therapy , fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients ( p < .001 ) . The mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients ( p < .001 ) . Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients ( p < .001 ) . CONCLUSIONS Abrupt interruption of antidepressant therapy for 5 - 8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline , with few symptoms seen with fluoxetine BACKGROUND 60%-90 % of patients with a primary diagnosis of depression also experience symptoms of anxiety , and such patients have a poorer prognosis than those with uncomplicated depression . The serotonin selective reuptake inhibitors have demonstrated efficacy in the treatment of both depression and certain anxiety states . Furthermore , in a meta analysis of the paroxetine clinical trial data base of 2963 patients in whom depression predominated , there was a concomitant reduction in the Hamilton Rating Scale for Depression anxiety factor . The purpose of the present study was to prospect ively compare the efficacy of paroxetine and clomipramine in patients specifically selected for coexisting depression and anxiety . METHOD This was a 12-week , double-blind , parallel-group trial comparing paroxetine 20 - 40 mg/day with clomipramine 75 - 150 mg/day in 1002 patients with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score > or = 20 and a Clinical Anxiety Score ( CAS ) > or = 11 after a 3 - 7 day placebo run-in period . RESULTS Both paroxetine and clomipramine reduced the MADRS and CAS ratings at 2 , 6 , and 12 weeks and at endpoint , with no significant differences between treatment groups at any time point . CGI severity of illness and global improvement ratings were also similar throughout the trial ; however , there was a statistically significant difference in the CGI efficacy index at 6 weeks and at endpoint , favoring paroxetine ( p = .015 and p = .015 , respectively ) . Paroxetine result ed in fewer treatment-emergent adverse experiences and related withdrawals than clomipramine ( p = .025 and p = .008 , respectively ) . The number of serious adverse experiences was not significantly different in the paroxetine group compared with the clomipramine group ( 14 [ 2.8 % ] vs. 27 [ 5.4 % ] ) , but did approach statistical significance ( p = .056 ) . Anticholinergic-emergent adverse experiences were reported twice as frequently by patients in the clomipramine group as in the paroxetine group ( 36.1 % vs. 18.6 % ) . CONCLUSION There was no evidence of any significant difference in efficacy between paroxetine and clomipramine in patients with coexisting depression and anxiety . However , paroxetine was better tolerated as shown by total treatment-emergent adverse experiences , anticholinergic adverse experiences , and withdrawals due to adverse experiences BACKGROUND Depression is a serious and widespread emotional disorder among the elderly . This study compared the efficacy and safety of bupropion sustained release ( SR ) with the selective serotonin reuptake inhibitor paroxetine in the treatment of major depression in elderly out patients . METHOD Elderly ( > or = 60 years ) out patients with major depressive disorder ( DSM-IV criteria ) were evaluated in this 6-week multicenter , r and omized , double-blind study comparing bupropion SR , 100 - 300 mg/day , and paroxetine , 10 - 40 mg/day . Efficacy was assessed by changes in scores on the Hamilton Rating Scales for Depression ( HAM-D ) and Anxiety ( HAM-A ) and the Clinical Global Impressions-Severity of Illness and -Improvement scales . Safety was assessed by monitoring adverse events , vital signs , and body weight . RESULTS A total of 100 patients ranging in age from 60 to 88 years were r and omly assigned to treatment with bupropion SR ( N = 48 ) or paroxetine ( N = 52 ) . Measurements of efficacy were similar between the 2 treatment groups , with both groups showing improved scores on all depression rating scales . Headache , insomnia , dry mouth , agitation , dizziness , and nausea occurred in > 10 % of patients in both groups ; somnolence , diarrhea , constipation , and anorexia occurred in > 10 % of patients in the paroxetine group . No statistically significant differences between groups in vital signs or weight were found . CONCLUSION Both bupropion SR and paroxetine were safe and effective for the treatment of depression in the elderly . Because of its favorable side effect profile , bupropion SR may provide a safe and effective nonserotonergic treatment alternative that is well suited as an antidepressant for the elderly The primary objective of this multicentre , r and omized , double-blind study carried out in France was to compare the efficacy and safety of a 6-week treatment with paroxetine ( 20 mg/day ) or mianserine ( 30 mg/day ) in geriatric hospitalized or ambulatory patients ( > or = 60 years ) treated for a major depressive disorder ( according to DSM III-R ) . A secondary objective was to discriminate those items predicting the response to an agent according to its serotoninergic or noradrenergic pharmacologic profile . The tool used for this latter purpose was the Aubin-Jouvent-Rating-Scale ( AJRS ) which was design ed to assess the deficit of serotonin : this is a scale with 10 items , some of them regrouped into a " general " factor ( irritability , sudden mood change , impatience , aggressivity ) or a " depression " factor ( pain , anxiety , suicidal ideas ) with additional items related to sleep disorders , abnormalities in eating behavior and inability to tolerate isolation . In the perspective of this assessment , paroxetine was chosen due to its potential to inhibit serotonin re-uptake , as compared to mianserin which blocks presynaptic alpha-adrenergic receptors with negligible action on serotonin . This was a multicenter study carried out in France in 50 hospital or private practice psychiatrists . The assessment criteria included the MADRS , the AJRS , the COVI 's anxiety scale , the Folstein 's Mini-mental state ( MMS ) as well as a global assessment by the investigator at the end of the study . Safety was measured with a nondirective question naire , routine laboratory tests as well as a global assessment by the investigator . The primary efficacy criteria was the change in the MADRS global score . Statistical analysis included chi-square or Fisher 's test as well as Student 's and Wilcoxon tests for comparability at baseline , and analysis of variance for the changes in scores as during the study . A total of 116 patients was r and omised ( paroxetine : 54 ; mianserine : 62 ) , of whom 96 completed the study ( paroxetine : 43 ; mianserine : 53 ) . With the exception of MADRS moderately higher in the paroxetine group , both groups were comparable at baseline . After 6 weeks of treatment , a marked improvement was recorded in both groups for all criteria except MMS ; there was a consistent tendency favouring paroxetine which reached statistical significance for the COVI ' scale ( p = 0.001 ) . For a given criterion , the difference paroxetine versus mianserine appeared related to the score at baseline ; it was also more marked in those patients with a AJRS baseline score > or = 20 with a difference for MADRS reduction of marginal significance in favor of paroxetine ( p = 0.061 ) . As regards safety , at least one adverse event was reported in 31.5 % of the patients receiving paroxetine versus 41.9 % in those receiving mianserin ( NS ) ; premature withdrawal related to an adverse event was reported in 11.1 % of the patients in the paroxetine group versus 12.9 % in the mianserin group . No abnormality of clinical significance was reported in either group concerning laboratory tests . In conclusion , this study confirmed the therapeutic value and good safety of paroxetine as an antidepressant in geriatric population s , especially when exist a concomitant anxiety or symptoms likely to reflect a deficit of serotonine ( irritability , emotional lability , restlessness , aggressivity ) and to predict a good response to an agent such as this one INTRODUCTION Sexual dysfunction is common with serotonergic antidepressants , including selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-norepinephrine reuptake inhibitors ( SNRIs ) , and does not resolve in most patients . Vortioxetine , an antidepressant with a multimodal mechanism of action , has shown low rates of sexual dysfunction in previous major depressive disorder ( MDD ) trials . AIM This study compared the effects of vortioxetine and escitalopram on sexual functioning in adults with well-treated MDD experiencing treatment-emergent sexual dysfunction ( TESD ) . METHODS Participants treated with , and responding to , citalopram , paroxetine , or sertraline were r and omized to switch to either vortioxetine ( 10/20 mg ; n = 225 ) or escitalopram ( 10/20 mg ; n = 222 ) for 8 weeks . Sexual function was assessed using the Changes in Sexual Functioning Question naire Short Form ( CSFQ-14 ) , and antidepressant efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions ( CGI ) scale , and Profile of Mood States brief form ( POMS-brief ) . Safety and tolerability were also assessed . MAIN OUTCOME MEASURES The primary endpoint was change from baseline in the CSFQ-14 total score after 8 weeks of treatment . The MADRS , CGI , and POMS-brief were used to assess antidepressant efficacy . Safety was assessed via adverse events , vital signs , electrocardiograms , laboratory values , weight , and physical examination findings . RESULTS Vortioxetine showed significantly greater improvements in CSFQ-14 total score ( 8.8 ± 0.64 , mean ± st and ard error ) vs. escitalopram ( 6.6 ± 0.64 ; P = 0.013 ) . Benefits vs. escitalopram were significant on four of five dimensions and all three phases of sexual functioning assessed by the CSFQ-14 ( P < 0.05 ) . Antidepressant efficacy continued in both groups , with similar , but slight , improvements in MADRS and CGI scores . Vortioxetine and escitalopram had similar clinical efficacy profiles in this study , with safety profiles similar to previous trials . Nausea ( n = 9 , 4.0 % ) was the most common treatment-emergent adverse event leading to discontinuation of vortioxetine . CONCLUSION Switching antidepressant therapy to vortioxetine may be beneficial for patients experiencing sexual dysfunction during antidepressant therapy with SSRIs Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage Abstract Objective : To examine the factors that contribute to the occurrence of the discontinuation syndrome in patients who have received paroxetine to treat depression . Method : The clinical records of individuals from the outpatient units of two centres in the western area of Japan who had had a single episode of major depressive disorder ( MDD ) and had completed monotherapy with paroxetine in the previous 5 years were retrospectively review ed . All patients had been diagnosed with MDD according to the DSM-IV criteria . The patients were divided into two groups , according to whether or not they had experienced the discontinuation syndrome when paroxetine was stopped . The syndrome was diagnosed according to st and ard criteria for the SSRI discontinuation syndrome . The two groups were compared for sex , age , maintenance dosage of paroxetine , duration of treatment with paroxetine , presence of adverse reactions in the early phase of treatment with paroxetine , and method of paroxetine withdrawal ( abrupt or tapered ) . Results : Of the 385 patients included in the review , 41 patients experienced the discontinuation syndrome . The occurrence of the discontinuation syndrome did not correlate with sex , maintenance dosage of paroxetine or duration of treatment with the drug . However , there was a relationship between the method of drug withdrawal and the occurrence of the discontinuation syndrome , with the syndrome occurring significantly more frequently in those patients in whom paroxetine was abruptly discontinued . There was an association between the occurrence of the discontinuation syndrome and age , but this association seemed to have been caused by the fact that younger patients were more inclined to abruptly stop taking the medication . It was also found that the discontinuation syndrome occurred at a significantly higher rate in patients who had experienced adverse reactions to paroxetine in the early phase of treatment . Conclusion : The discontinuation syndrome in patients taking paroxetine  was more likely to occur in those patients who stopped taking the drug abruptly . The occurrence of the discontinuation syndrome was also correlated with younger age , but this association seemed to be secondary to the fact that younger patients tended to be more likely to abruptly stop taking the medication . It appears that the discontinuation syndrome can be prevented by carefully tapering the dosage of paroxetine when treatment is withdrawn . Interestingly , the discontinuation syndrome was more likely to occur in those patients who experienced adverse reactions in the early phase of treatment with paroxetine . When the drug is discontinued , additional attention should be paid to patients who have presented with adverse reactions in the early phase of paroxetine therapy BACKGROUND Case reports and open studies have reported beneficial therapeutic effects of adding buspirone to a selective serotonin reuptake inhibitor ( SSRI ) in the management of treatment-refractory depression .  This is the first placebo-controlled study to evaluate the efficacy and safety of this combination . METHOD One hundred nineteen patients ( 82 women , 37 men ) who fulfilled criteria for a major depressive episode according to DSM-IV and who had failed to respond to a minimum of 4 weeks ( mean = 211 days ) of treatment with citalopram or paroxetine  were r and omly assigned to 4 weeks of treatment with an SSRI plus buspirone ( N = 58 ) or an SSRI plus placebo ( N = 61 ) . In addition , 97 patients participated in an optional open-label post study treatment phase with the SSRI plus buspirone for 2 weeks . The primary outcome measure was the score on the Clinical Global Impressions-Improvement ( CGI-I ) scale . RESULTS A total of 50.9 % of patients in the buspirone group and 46.7 % in the placebo group responded after 4 weeks of treatment . The difference in response rate was not statistically significant . No statistically significant differences were found in the frequency of adverse events . At the follow-up of the open SSRI plus buspirone treatment , 69.4 % of patients had responded . CONCLUSION Adding buspirone to an SSRI is a safe and well-tolerated drug regimen . This study failed to demonstrate any difference in efficacy between buspirone or placebo augmentation of an SSRI . It could be argued , however , that the study was inconclusive due to the unusually high placebo response Objective : This is a retrospective study to add to the existing body of clinical information regarding male sexual side effects associated with antidepressants . From the chart review , thirty-four out of eighty male patients were identified to have reported loss of libido , erectile difficulty , anorgasmia , and delayed ejaculation while receiving pharmacotherapy of selective serotonin reuptake blockers ( fluoxetine , paroxetine , and sertraline ) ; tricyclic antidepressants ( nortriptyline , imipramine , amitriptyline , desipramine , and clomipramine ) ; and a monoamine oxidase inhibitor ( phenelzine ) . Method : The authors also discussed the management of these sexual side effects by waiting for spontaneous remission , reducing the dosage level , and substituting the offending drug with other antidepressants . Results : This article underscores the underreported nature of antidepressant-associated sexual dysfunction , the high incidence of SSRI-associated sexual side effects , equal potentials in causing sexual side effects among the three SSRI 's , the low incidence rate of sexual adverse effects from bupropion , and the minimal need to add an antidote if the side effects are to be managed systematic ally . Conclusions : Finally , male sexual side effects can occur r and omly and involve any sexual phase r and omly , and the treatment approaches are similar , regardless of the types of sexual dysfunction associated with antidepressants BACKGROUND The cost-effectiveness of tricyclic antidepressants ( TCAs ) and selective serotonin reuptake inhibitors ( SSRIs ) has not been compared in a prospect i ve study in primary care . AIMS To determine the relative cost-effectiveness of TCAs , SSRIs and lofepramine in UK primary care . METHOD An open-label , three-arm r and omised trial with a preference arm . Practitioners referred 327 patients with incident depression . RESULTS No significant differences were found in effectiveness or cost-effectiveness . The numbers of depression-free weeks over 12 months ( on the Hospital Anxiety and Depression Scale ) were 25.3 ( 95 % CI 21.3 - 29.0 ) for TCAs , 28.3 ( 95 % CI 24.3 - 32.2 ) for SSRIs and 24.6 ( 95 % CI 20.6 - 28.9 ) for lofepramine .  Mean health service costs per patient were pound 762 ( 95 % CI 553 - 1059 ) for TCAs , pound 875 ( 95 % CI 675 - 1355 ) for SSRIs and pound 867 ( 95 % CI 634 - 1521 ) for lofepramine .  Cost-effectiveness acceptability curves suggested SSRIs were most cost-effective ( with a probability of up to 0.6 ) . CONCLUSIONS The findings support a policy of recommending SSRIs as first-choice antidepressants in primary care The aim of the present study was to test a possible effect of the monoamine oxidase A ( MAOA ) and serotonin receptor 2A ( 5-HT-2A ) gene variants on the antidepressant activity of fluvoxamine and paroxetine in a sample of major ( n = 248 ) and bipolar ( n = 195 ) depressives , with or without psychotic features . A total of 443 in- patients were treated with 300 mg fluvoxamine ( n = 307 ) or 20 - 40 mg paroxetine ( n = 136 ) for 6 wk . The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression ( HAMD ) . Allele variants were determined in each subject using a PCR-based technique . We observed a marginal association between 5-HT-2A variants and antidepressant response while MAOA genotypes were not associated . Possible stratification factors , such as sex , diagnosis , presence of psychotic features , HAMD scores at baseline , pindolol augmentation and SSRIs plasma levels did not significantly influence the observed results . The investigated MAOA and 5-HT-2A gene variants , therefore , do not seem to play a major role in SSRI antidepressant activity OBJECTIVE There is substantial evidence that depression constitutes a risk factor for type 2 diabetes mellitus . A recent study has shown that high salivary cortisol levels are associated with decreased insulin sensitivity in unmedicated , depressed patients . Further , antidepressive treatment might have differential effects on hypothalamus-pituitary-adrenal ( HPA ) system activity . Therefore , the aim of the present study was to examine whether insulin sensitivity improves during anti-depressive treatment in depressed patients with declining HPA system activity . METHOD Eighty in patients with an episode of major depressive disorder ( DSM-IV criteria ) were treated in a double-blind , r and omized protocol with either amitriptyline or paroxetine over a period of 5 weeks . After 6 drug-free days , an oral glucose tolerance test was performed on day 1 and again 35 days after antidepressive treatment . For quantification of free cortisol levels , saliva was obtained daily at 8:00 a.m. during weeks -1 ( washout ) and 5 . The study was conducted from May 2005 to December 2005 . RESULTS The insulin sensitivity index(Matsuda ) increased in only those patients who remitted from major depressive disorder as a result of treatment with either antidepressant ( F = 7.0 , df = 1,74 ; p < .01 ) , while correcting for body mass index . Further , cortisol concentrations declined in remitters and responders to amitriptyline ( F = 2.1 , df = 1,70 ; p < .05 ) , but not in any other subgroup . CONCLUSION Successful antidepressive treatment with either a selective serotonin reuptake inhibitor or a tricyclic substance increases the sensitivity to insulin in nondiabetic depressed patients . The herein presented longitudinal data do not exclude the HPA system as a major contributor to insulin resistance in depressed patients , but underscore the assumption of additional factors We assessed the tolerability and antidepressant response to citalopram in a group of patients who could not tolerate a recent trial of paroxetine therapy . Sixty-one out patients with major depressive disorder and a confirmed history of intolerance to paroxetine ( mean final dose : 26.7 mg/day ) were switched after at least a 1 week washout to citalopram therapy ( 20 mg/day ) . During the 6-week , open label treatment protocol , citalopram could be titrated up to a maximum dose of 40 mg/day . Response was evaluated using the Clinical Global Impressions CGI scale , the 24-item Hamilton Rating Scale for Depression , and several other measures of symptoms and quality of life . Fifty-three patients ( 87 % ) completed 6 weeks of citalopram therapy ( mean intent-to-treat dose : 23.9 mg/day ) . The specific side effects that were reported to be intolerable during the earlier paroxetine trial typically recurred only less than 30 % of the time during citalopram therapy ; only 6 patients ( 10 % ) dropped out because of adverse events . The intent-to-treat CGI response rate was 56 % at study endpoint ; 62 % of the completers responded . Significant improvement from pretreatment was observed on various symptom measures after two weeks of citalopram therapy . Citalopram therapy was well tolerated , and more than one half of the patients who began treatment improved significantly . Although further work is necessary to assess the relative merits of this within-class switching strategy ( as compared to other options ) , these data provide further evidence that the various selective serotonin reuptake inhibitors do not have interchangeable tolerability profiles We aim ed to evaluate the effectiveness of paroxetine and tadalafil combination in the treatment of  premature ejaculation ( PE ) . A total of 150 primary (lifelong)PE patients were r and omly distributed into three groups of 50 patients each . Group 1 received 20 mg paroxetine every day for 1 month , Group 2 received 20 mg tadalafil on dem and 2 h before intercourse , and Group 3 received paroxetine and tadalafil on dem and 2 h before intercourse . Intravaginal ejaculatory latency times ( IELT ) scores were evaluated at baseline , at the end of the first month of therapy and 1 month after discontinuation of the treatment , while International Index of Erectile Function ( IIEF ) question naire scores were evaluated both prior to and after the treatment . At the end of the first month of therapy , IELT scores were compared with the basal values and statistically significant changes were detected ( 60.6 ± 30.2–117.3 ± 67.3 , 68.5 ± 21.4–110.2 ± 37.3 , 71.56 ± 40.23–175.2 ± 60.2)(P < 0.01 ) . IELT scores after discontinuation of treatment were found to be close to the baseline IELT scores ( P > 0.05 ) . IIEF scores were evaluated both prior to and after the treatment , and no statistically significant difference was detected ( P > 0.05 ) . It is concluded that utilisation of selective serotonin reuptake inhibitors ( SSRI ) and phosphodiesterase‐5 inhibitors ( PDE5i ) combination before intercourse seems to provide significantly longer ejaculatory latency times as compared with SSRI alone for a long time in patients with PE This study evaluated the effects of serotonergic psychoactive agents on  gastrointestinal functions in healthy human subjects . Participants received one of four regimens in a r and omized , double-blind manner : buspirone , a 5-HT(1A ) receptor agonist ( 10 mg twice daily ) ; paroxetine , a selective serotonin reuptake inhibitor ( 20 mg daily ) ; venlafaxine-XR , a selective serotonin and norepinephrine reuptake inhibitor ( 75 mg daily ) ; or placebo for 11 days . Physiological testing performed on days 8 - 11 included scintigraphic assessment of gastrointestinal and colonic transit , the nutrient drink test , and assessment of the postpr and ial change in gastric volume .  Fifty-one healthy adults ( 40 females , 11 males ) participated in this study . No effects on gastric emptying or colonic transit were identified with any agent . Small bowel transit of a solid meal was accelerated by paroxetine . Buspirone decreased postpr and ial aggregate symptom and nausea scores .  Venlafaxine-XR increased the postpr and ial change in gastric volume .  Buspirone , paroxetine , and venlafaxine-XR affect upper gastrointestinal functions in healthy humans . These data support the need for clinical and physiological studies of these agents in functional gastrointestinal disorders BACKGROUND This r and omized , open-label , rater-blinded , multicenter study compared treatment outcomes with the serotonin-norepinephrine reuptake inhibitor ( SNRI ) venlafaxine extended release ( ER ) with selective serotonin reuptake inhibitors ( SSRIs ) in primary care patients with major depressive disorder . METHOD Study data were collected from November 29 , 2000 , to March 4 , 2003 . Out patients who met diagnostic criteria for major depressive disorder according to the Mental Health Screener , a computer-administered telephone interview program that screens for the most common mental disorders , and had a total score on the 17-item Hamilton Depression Rating Scale ( HDRS(17 ) ) ≥ 20 were r and omly assigned to receive up to 6 months of open-label venlafaxine ER 75 - 225 mg/d ( n = 688 ) or an SSRI ( n = 697 ) : fluoxetine 20 - 80 mg/d , paroxetine 20 - 50 mg/d , citalopram 20 - 40 mg/d , and sertraline 50 - 200 mg/d . The primary outcome was remission ( HDRS(17 ) score ≤ 7 ) at study end point using the last-observation-carried-forward method to account for early termination . A mixed-effects model for repeated measures ( MMRM ) analysis evaluated secondary outcome measures . RESULTS Fifty-one percent of patients completed the study . Month 6 remission rates did not differ significantly for venlafaxine ER and the SSRIs ( 35.5 % vs 32.0 % , respectively ; P = .195 ) . The MMRM analysis of HDRS(17 ) scores also did not differ significantly ( P = .0538 ) . Significant treatment effects favoring the venlafaxine ER group were observed for remission rates at days 30 , 60 , 90 , and 135 and a survival analysis of time to remission ( P = .006 ) , as well as Clinical Global Impressions-severity of illness scale ( P = .0002 ) ; Hospital Anxiety and Depression Scale-Anxiety subscale ( P = .03 ) ; 6-item Hamilton Depression Rating Scale , Bech version ( P = .009 ) ; and Quick Inventory of Depressive Symptomatology-Self-Report ( P = .0003 ) . CONCLUSIONS Remission rates for patients treated with venlafaxine ER or an SSRI did not differ significantly after 6 months of treatment . Results of most secondary analyses suggested that SNRI treatment had a greater antidepressant effect versus the SSRIs studied We report results from a multicenter , placebo-controlled , r and omized , double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in out patients with major depression . Across five U.S. sites , 128 out patients ( mean age : 41.3 + /- 12.6 ; 63 men and 65 women ) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994 . All 128 patients completed a 1-week placebo washout period , and were then r and omized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day ( n = 55 ) , fluoxetine up to 80 mg/day ( n = 54 ) , or placebo ( n = 19 ) . Subjects were evaluated weekly for the first 4 weeks , then at weeks 6 , 9 , and 12 with the 21-item HAMD and the Covi Anxiety Scale . There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity , as well as in the degree of depression and anxiety improvement . There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients . In summary , our results , although limited by the lack of a significant difference from placebo in treatment outcome , suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed out patients , as well as similar safety and tolerability profiles CONTEXT Only about 60 % of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor ( SSRI ) . There are no data to guide clinicians on subsequent treatment strategy . OBJECTIVE To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI .  DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI , conducted at 6 US academic and community clinics from 2000 - 2006 . INTERVENTIONS Twelve weeks of : ( 1 ) switch to a second , different SSRI ( paroxetine , citalopram , or fluoxetine , 20 - 40 mg ) ; ( 2 ) switch to a different SSRI plus cognitive behavioral therapy ; ( 3 ) switch to venlafaxine ( 150 - 225 mg ) ; or ( 4 ) switch to venlafaxine plus cognitive behavioral therapy . MAIN OUTCOME MEASURES Clinical Global Impressions-Improvement score of 2 or less ( much or very much improved ) and a decrease of at least 50 % in the Children 's Depression Rating Scale-Revised ( CDRS-R ) ; and change in CDRS-R over time . RESULTS Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate ( 54.8 % ; 95 % confidence interval [ CI ] , 47%-62 % ) than a medication switch alone ( 40.5 % ; 95 % CI , 33%-48 % ; P = .009 ) , but there was no difference in response rate between venlafaxine and a second SSRI ( 48.2 % ; 95 % CI , 41%-56 % vs 47.0 % ; 95 % CI , 40%-55 % ; P = .83 ) . There were no differential treatment effects on change in the CDRS-R , self-rated depressive symptoms , suicidal ideation , or on the rate of harm-related or any other adverse events . There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment . CONCLUSIONS For adolescents with depression not responding to an adequate initial treatment with an SSRI , the combination of cognitive behavioral therapy and a switch to another antidepressant result ed in a higher rate of clinical response than did a medication switch alone . However , a switch to another SSRI was just as efficacious as a switch to venlafaxine and result ed in fewer adverse effects . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00018902 OBJECTIVE This study examined whether a selective serotonin reuptake inhibitor ( paroxetine ) had comparable efficacy but greater tolerability than a tricyclic antidepressant ( imipramine ) in depressed patients with HIV infection . METHOD Seventy-five HIV-positive patients ( 45 % of whom had AIDS ) were blindly and r and omly assigned to receive paroxetine ( N = 25 ) , imipramine ( N = 25 ) , or placebo ( N = 25 ) in a 12-week trial . The Hamilton Anxiety Rating Scale , the Hamilton Depression Rating Scale , the Clinical Global Impression scale , and the SAFETEE general inquiry ( for safety and tolerability ) were administered at weeks 2 , 4 , 6 , 8 , and 12 . RESULTS Fifty-six ( 75 % ) of the 75 patients completed 6 weeks and 34 ( 45 % ) completed 12 weeks of the trial . The mean daily doses of both paroxetine ( 33.9 mg ) and imipramine ( 162.5 mg ) were significantly more effective than placebo ; they were comparably effective at weeks 6 , 8 , and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial ( for them , only imipramine was superior to placebo at week 12 ) . There were significantly more dropouts due to side effects from imipramine ( 48 % ) than from both paroxetine ( 20 % ) and placebo ( 24 % ) . CONCLUSIONS Depressed patients with HIV infection  responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression . Because paroxetine was much better tolerated than imipramine , its overall effectiveness may be greater . However , because of the small study group and the high attrition rate , these findings can not be generalized and may need replication in a larger study group Selective serotonin re-uptake inhibitors ( SSRIs ) and cognitive behavioral therapies ( CBTs ) are both considered as first-line treatments for panic disorder , but the advantages of a combined therapy have yet to be definitively demonstrated . We evaluated in this pilot study the effects of combining SSRIs ( vs. a placebo ) with a very brief form of cognitive-behavioral therapy provided to all participants . Thirty-three subjects with DSM-IV panic disorder , with or without agoraphobia , were r and omized to receive either paroxetine or a placebo with flexible dosing ( 10 - 50 mg/day ) . Medication visits were brief ( 15 min ) , infrequent ( 6 in total ) and non-directive . An expert cognitive-behavior therapist administered one initial 45-min session and one subsequent 30-min session of very brief CBT ( vbCBT ) at weeks 5 and 7 , respectively . Sessions were supplemented with educational and directive reading material s. Patients in both groups ( i.e. vbCBT+paroxetine ; vbCBT+placebo ) improved similarly and substantially on most measures during the 10 weeks of acute treatment . At week 10 , the proportion of panic-free patients was significantly higher in the paroxetine-treated group than in the placebo group ( 80 vs. 25 % ; P<0.007 ) , as was the proportion of subjects who rated themselves as ' very much improved ' at week 10 ( 60 vs. 13 % ; P<0.017 ) . These findings point to the need for additional studies to confirm the effectiveness of very brief forms of CBT , and to document the circumstances in which combined treatment with an SSRI would be warranted OBJECTIVE This study was design ed to determine the minimum paroxetine dose effective for treating panic disorder . METHOD Of 425 patients with DSM-III-R panic disorder with or without agoraphobia who underwent a 2-week drug-free screening period , 278 patients were r and omly assigned to double-blind treatment with a 10-week course of placebo or paroxetine at a dose of 10 , 20 , or 40 mg/day . RESULTS At 40 mg/day , paroxetine was superior to placebo across the majority of outcome measures . Despite a mean of 9.5 to 11.6 full panic attacks during the screening period , 86.0 % of the patients taking 40 mg of paroxetine , 65.2 % of those taking 20 mg , 67.4 % of those taking 10 mg , and 50.0 % of the placebo-treated patients were free of full panic attacks during the 2 weeks ending at week 10 . The 40-mg paroxetine group experienced significantly greater global improvement than the placebo group and significantly greater improvement in frequency of full and limited-symptom panic attacks , intensity of full panic attacks , phobic fear , anxiety , and depressive symptoms , usually evident by week 4 . All doses of paroxetine were well tolerated , and adverse effects were consistent with those associated with selective serotonin reuptake inhibitors . CONCLUSIONS Paroxetine is an effective and well-tolerated short-term treatment of panic disorder . The minimum dose demonstrated to be significantly superior to placebo was 40 mg/day , although some patients did respond at lower doses BACKGROUND Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors ( SSRIs ) have proved to be effective in the treatment of panic disorder . The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone . METHOD 161 patients with panic disorder with or without agoraphobia ( DSM-IV criteria ) underwent a manual-guided cognitive-behavioral therapy of 15 sessions . Forty-three unsuccessfully treated patients from this group were included in a double-blind , placebo-controlled , next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo . RESULTS Overall , patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior ( p < .05 ) and anxiety discomfort ( p < .01 ) , whereas patients in the cognitive-behavioral therapy plus placebo condition did not . Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition , from 0.4 to 1.0 . CONCLUSION Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality . The importance of timely evaluation of treatment results is emphasized BACKGROUND Inositol has been reported to be an effective treatment in depression , and we hypothesized that inositol addition might enhance or speed up response to  serotonin selective reuptake inhibitors ( SSRI ) . METHODS Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol .  Hamilton Depression Rating Scale was used as an assessment tool at baseline , and 1 , 2 , 3 , and 4 weeks . RESULTS No significant difference was found between the two treatment groups . CONCLUSIONS Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [ e.g. , monoamine oxidase inhibitors ( MAOI ) plus tricyclic antidepressants ( TCA ) , TCA plus lithium ] . By contrast , augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol
We found no clear evidence that paroxetine was more or less effective compared with other antidepressants at increasing response to treatment at acute ( six to 12 weeks ) , early ( one to four weeks ) , or longer term follow-up ( four to six months ) .
Paroxetine was associated with a lower rate of adverse events than amitriptyline , imipramine and older ADs as a class , but was less well tolerated than agomelatine and hypericum .
Some possibly clinical ly meaningful differences between paroxetine and other ADs exist , but no definitive conclusions can be drawn from these findings .
In terms of early response to treatment ( one to four weeks ) there was moderate quality of evidence that mirtazapine was better than paroxetine and that paroxetine was better than reboxetine .
However there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any time point .
BACKGROUND Paroxetine is the most potent inhibitor of the reuptake of serotonin of all selective serotonin reuptake inhibitors ( SSRIs ) and has been studied in many r and omised controlled trials ( RCTs ) .
However , these comparative studies provided contrasting findings and systematic review s of RCTs have always considered the SSRIs as a group , and evidence applicable to this group of drugs might not be applicable to paroxetine alone .
The present systematic review assessed the efficacy and tolerability profile of paroxetine in comparison with tricyclics ( TCAs ) , SSRIs and newer or non-conventional agents .
OBJECTIVES 1 .
To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of Major Depressive Disorder.2  .
To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.3 .
To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents .