Antidepressant treatment for post-natal depression. Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group. A randomized controlled clinical trial comparing "guideline exposed" and "guideline naive" physicians in respect to dosage selection and treatment outcome with doxepin in depressive disorders. Efficacy of Computer-Aided Dosing of Warfarin Among Patients in a Rehabilitation Hospital A double-blind study of fluoxetine and imipramine in major depression. Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial. Efficacy and mood conversion rate during long-term fluoxetine v. lithium monotherapy in rapid- and non-rapid-cycling bipolar II disorder. An analysis of systematic reviews indicated low incorpororation of results from clinical trial quality assessment. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. How many Cochrane reviews are needed to cover existing evidence on the effects of healthcare interventions? Continuation and Maintenance Use of Antidepressants in Recurrent Depression A comparative trial of fluoxetine versus trazodone in outpatients with major depression. Commentary on the Cochrane Review of acupuncture and assisted conception. Safe use of SSRIs in young adults: how strong is evidence for new suicide warning? Resolution of sexual dysfunction during double-blind treatment of major depression with reboxetine or paroxetine Male Sexual Side Effects Associated with Antidepressants: A Descriptive Clinical Study of 32 Patients Testosterone Versus Fluoxetine for Depression and Fatigue in HIV/AIDS: A Placebo-Controlled Trial Self-help interventions for depressive disorders and depressive symptoms: a systematic review Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. Adequacy and Duration of Antidepressant Treatment in Primary Care Prevalence and rates of recognition of depressive disorders in internal medicine outpatient departments of 23 general hospitals in Shenyang, China. A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics Randomized Clinical Trial of a Primary Care Internet-based Intervention to Prevent Adolescent Depression: One-year Outcomes. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. The International Personality Disorder Examination. The World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration international pilot study of personality disorders. Systematic Reviews of Diagnostic Test Accuracy Three-year outcomes for maintenance therapies in recurrent depression. Risk factors for antidepressant-related switch to mania. Do antidepressants selectively suppress spontaneous (unexpected) panic attacks? A replication. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder. A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. Protocol for a systematic review of psychological interventions for cancer-related fatigue in post-treatment cancer survivors Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial. Risperidone for Treatment-Refractory Major Depressive Disorder Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder. Influence of fluoxetine on positive and negative affect in a clinic-based smoking cessation trial Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomized comparison of fluoxetine and a tricyclic antidepressant. How fast does oral dexamethasone work in mild to moderately severe croup? A randomized double‐blinded clinical trial Amitriptyline Versus Amitriptyline Combined With Fluoxetine in the Preventative Treatment of Transformed Migraine: A Double‐Blind Study Moclobemide versus fluoxetine for a major depressive episode [Penfluridol. Results of a year-long clinical trial]. Quality of treatment and disability compensation in depression: comparison of 2 nationally representative samples with a 10-year interval in Finland. Intensive Nutritional Counselling in Bulimia Nervosa: A Role for Supplementation with Fluoxetine? Psychometric testing of fatigue instruments for use with cancer patients. Moclobemide versus fluoxetine for a major depressive episode A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression. Effects of high and low dosage of haloperidol on the brain in relation to schizophrenic thought disorder. [Factor XIII in the treatment of postoperative refractory wound-healing disorders. Results of a controlled study]. A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. Long-term effects from a randomized trial of two public health preventive interventions for parental depression. Mapping randomized controlled trials of treatments for eczema - The GREAT database (The Global Resource of Eczema Trials: a collection of key data on randomized controlled trials of treatments for eczema from 2000 to 2010) [A comparison between low doses of amitriptyline and low doses of fluoxetin used in the control of depression in patients suffering from Parkinson's disease]. Beliefs about the causes of depression and recovery and their impact on adherence, dosage, and successful tapering of antidepressants Is the Comparison between Exercise and Pharmacologic Treatment of Depression in the Clinical Practice Guideline of the American College of Physicians Evidence-Based? Assessing the adequacy of past antidepressant trials: a clinician's guide to the antidepressant treatment response questionnaire. Low dosage lithium augmentation in venlafaxine resistant depression: an open-label study. Fluoxetine in posttraumatic stress disorder. Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects Dosage adjustment and clinical outcomes of long-term use of high-dose tobramycin in adult cystic fibrosis patients. Efficacy of an acceptance-based behavior therapy for generalized anxiety disorder: evaluation in a randomized controlled trial. Methodological developments in searching for studies for systematic reviews: past, present and future? Predictors of persistence of comorbid generalized anxiety disorder among veterans with major depressive disorder. [Efficacy and safety of fluoxetine versus clomipramine in ambulatory patients with a depressive syndrome in a clinical trial with private practitioners]. Use of topiramate, a new anti-epileptic as a mood stabilizer. Comparison of three methods to assess therapeutic quality control of treatment with vitamin K antagonists. Reliability of point‐of‐care prothrombin time testing in a community clinic: a randomized crossover comparison with hospital laboratory testing Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial. Predictors of relapse in a prospective study of fluoxetine treatment of major depression. 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BACKGROUND : Postnatal depression is a common disorder , which can have profound short and long term effects on maternal morbidity , the new infant and the family as a whole . Social factors appear to be particularly important in the aetiology and prognosis of postnatal depression and treatment is often largely social support and psychological interventions . It is not known whether antidepressants are an effective and safe choice for treatment of this disorder . OBJECTIVES : To evaluate the effectiveness of different antidepressant drugs  and compare their effectiveness with other forms of treatment . To assess any adverse effects of antidepressants in the mother or the nursing baby . SEARCH STRATEGY : The registers of clinical trials maintained and up date d by the Cochrane Depression , Anxiety and Neurosis Group and the Cochrane Pregnancy and Childbirth Group were search ed . Other data bases ( outlined below ) were also search ed and contacts were made with pharmaceutical companies and experts in the field . SELECTION CRITERIA : All trials were considered in which women with depression in the first six months postpartum were r and omised to receive antidepressants alone or in combination with another treatment , or to receive any other treatment including placebo . DATA COLLECTION AND ANALYSIS : Data was extracted independently from the trial reports by the review ers . Missing information was requested from investigators wherever possible . Data was sought to allow an " intention to treat " analysis . MAIN RESULTS : Only one trial could be included in this review , leaving most of the objectives of the review unfulfilled . Appleby et al ( 1997 ) reported that Fluoxetine was significantly more effective than placebo and , after an initial session of counselling , as effective as a full course of cognitive-behavioural counselling in the treatment of postnatal depression . There was no interaction between medication and counselling . REVIEW ER 'S CONCLUSIONS : Women with postnatal depression can be effectively treated with fluoxetine , which is as effective as a course of cognitive-behavioural counselling in the short-term . However , more trials with a longer follow-up period are needed to compare different antidepressants in the treatment of postnatal depression , and to compare antidepressant treatment with psychosocial interventions .  This is an area that has been neglected despite the large public health impact described above OBJECTIVE Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both , we investigated whether tryptophan , an amino acid with both antidepressant-augmenting and hypnotic effects , would benefit patients with depression at the beginning of treatment with fluoxetine .  DESIGN R and omized , double-blind , placebo-controlled trial . PATIENTS Thirty individuals with major depressive disorder . INTERVENTIONS Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan ( 2 to 4 g per day ) or placebo . OUTCOME MEASURES Mood was assessed using the 29-item Hamilton Depression Rating Scale ( HDRS-29 ) and the Beck Depression Inventory ( BDI ) . Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using st and ard procedures . RESULTS During the first week of treatment , there was a significantly greater decrease in HDRS-29 depression scores , and a similar trend in BDI scores , in the tryptophan/fluoxetine group than in the placebo/fluoxetine group . No significant differences were noted at later time points . With respect to sleep measures , there was a significant group-by-time interaction for slow-wave sleep at week 4 . Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group , but not in the tryptophan/fluoxetine group . No cases of serotonin syndrome occurred , and the combination was well tolerated , although the 4 g per day dosage of tryptophan produced daytime drowsiness . CONCLUSIONS Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep . Further large-scale studies are needed to confirm these initial findings OBJECTIVE To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed in patients and out patients . METHOD Patients with a major depressive episode ( DSM-III-R ) , a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) , and > or=2 on HAM-D Item 1 ( depressed mood ) were r and omly assigned to a 6-week treatment with either mirtazapine ( N=66 , 15 - 60 mg/day ) or fluoxetine ( N=67 , 20 - 40 mg/day ) . The upper limit of the mirtazapine dose range was above the dose range approved in the United States ( 15 - 45 mg/day ) . Efficacy was evaluated by the HAM-D , Clinical Global Impressions , the Visual Analogue Mood Rating Scale ( VAMRS ) , and the Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method . RESULTS Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group . The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period , reaching statistical significance at days 21 and 28 . At assessment s from day 21 and onward , the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points , the magnitude of difference usually seen between an efficacious antidepressant drug and placebo . Mean dosages at weeks 1 - 4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine ; the respective dosages at weeks 5 - 6 were 56.3 mg and 35.8 mg . Similar numbers of patients dropped out due to adverse events ; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group . CONCLUSION We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy INTRODUCTION Can prescribing of insufficient dosages and outcome of treatment with antidepressants in routine care be improved by guidelines ? METHODS 161 general practitioners and 162 psychiatrists in private practice documented 1319 patients , receiving doxepin for individual clinical reasons . Physicians were r and omly divided into a guideline exposed and a control group . All physicians treated their patients according to individual clinical considerations . RESULTS Average maximum daily dosage was 83 mg/d in the control and 95 mg/d in the intervention group ( F=19.15 ; p<0 ) . Only 3 % of patients in both groups got the recommended dosage of 150 mg/d . Guideline exposure result ed in increased dosages preferably for milder forms of depression and in comparatively lower rates of improvement . CONCLUSION Guideline exposure did not reach its goal in respect to the recommended dosage . It missed its goal in respect to improvement of outcome and even showed negative effects . Guidelines should be evidence -based not only by referring to literature review s but by testing their clinical effects in controlled clinical trials Mitra R , Marciello MA , Brain C , Ahangar B , Burke DT : Efficacy of computer-aided dosing of warfarin among patients in a rehabilitation hospital . Am J Phys Med Rehabil 2005;84:423–427 . Objective : To determine whether computer-aided dosing of warfarin is superior to physician dosing to maintain a patient in a rehabilitation hospital within a target international normalized ratio goal . Design : R and omized , double-blinded , clinical trial in an inpatient rehabilitation hospital . A total of 30 consecutive patients admitted receiving warfarin were r and omized to either clinician dosing  or computer-aided warfarin dosing for the duration of their hospitalization . The main outcome measures included the percentage of days in a therapeutic anticoagulation range and the number of blood draws .  Exclusion criteria included short length of stay ( n = 110 , 39 % ) and a physician declared international normalized ratio target range of < 2.0 ( n = 67 , 23 % ) . A total of 73 patients were excluded because of heme-positive stools at admission , recent gastrointestinal bleed , early discharge or consent refusal .  Dawn AC software was used to determine warfarin dosage and frequency of blood draws to maintain a target international normalized ratio of 2.0–3.0 for the computer-dosed group ( n = 14 ) . Several physicians recommended warfarin dosages for the second group ( n = 16 ) . Two were dropped from the computer model secondary to lost data files for these two patients . Results : Computer-aided dosing of warfarin result ed in 61.7 % of days within the therapeutic range ( international normalized ratio , 2–3 ) , whereas clinician dosing result ed in only 44.1 % . There were no significant differences in the number of blood draws or demographic variables between the two groups . Conclusion : Computers were significantly better at maintaining patients within a therapeutic international normalized ratio range than physicians . There were no significant differences in the number of recommended blood draws Eighteen out patients with major depression ( diagnosis was made according to DSM-III criteria ) were treated in a 5-week double-blind parallel group comparison of the new antidepressant fluoxetine with imipramine . From these results it can be shown that the drugs were comparable in efficacy , although because of the small sample size a moderate clinical difference between treatments may not have been detected . Imipramine and fluoxetine have already been compared in other studies , but never at such a low dosage ( 20 mg ) for fluoxetine . At this dosage the fluoxetine  safety profile seems to be very different from previous scheduled studies with higher dosages . In fact clinical efficacy seems to remain comparable while side-effects are significantly less frequent As many as 45 % of patients with major depressive episode also meet DSM-IV criteria for bipolar II ( BP II ) disorder . Although some clinicians advocate using a mood stabilizer in treating BP II depression , antidepressant monotherapy has been less well studied in this disorder . As part of a prospect i ve , placebo-controlled , relapse-prevention study in 839 patients , the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar ( UP ) major depression was retrospectively examined . Eighty-nine BP II patients ( mean age , 41+/-11 years ) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients ( mean age , 39+/-11 years ) . All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks . Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks . Remitted patients were then r and omly assigned to receive double-blind treatment with one of the following : ( 1 ) fluoxetine 20 mg daily for 52 weeks ; ( 2 ) fluoxetine for 38 weeks , then placebo for 14 weeks ; ( 3 ) fluoxetine for 14 weeks , then placebo for 38 weeks ; or ( 4 ) placebo for 52 weeks . Antidepressant efficacy was similar in BP and UP patients during short-term therapy . Discontinuation for lack of efficacy was lower in BP II ( 5 % ) than in UP ( 12 % ) patients ( p = not significant [ NS ] ) , whereas dropouts for adverse events were similar in BP II ( 11 % ) and UP ( 9 % ) patients . During long-term relapse-prevention therapy , relapse rates were similar in BP II and UP patients ( p = NS ) . During short-term fluoxetine therapy , three BP II ( 3.8 % ) versus no matched UP ( p = NS ) and 0.3 % unmatched UP ( p = 0.01 ) patients had a " manic switch . " During long-term fluoxetine therapy , one ( 2 % ) BP II and three ( 1 % ) unmatched UP patients ( one taking placebo ) had a manic switch ( p = NS ) . In conclusion , fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate . Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder BACKGROUND Previous small trials have suggested that nefazodone does not suppress rapid-eye-movement ( REM ) sleep or increase REM latency in depressed patients , in contrast to fluoxetine . The effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures were directly compared in this 8-week , multicenter , double-blind , r and omized , parallel-group study . METHOD Forty-four out patients with moderate to severe , nonpsychotic major depressive disorder ( DSM-III-R ) and insomnia were r and omly assigned to receive nefazodone ( Days 1 - 7 , 200 mg/day ; Days 8 - 56 , 400 mg/day ) or fluoxetine ( Days 1 - 56 , 20 mg/day ) . Sleep measures were obtained at baseline , while patients were unmedicated , and at Weeks 2 , 4 , and 8 of treatment . RESULTS In 43 evaluable patients ( 23 nefazodone , 20 fluoxetine ) , nefazodone and fluoxetine demonstrated similar antidepressant efficacy . All significant values were p < .05 . Fluoxetine significantly decreased sleep efficiency and REM sleep and increased number of awakenings , Stage 1 sleep , and REM latency compared with baseline . In contrast , nefazodone significantly decreased percentage of awake and movement time and did not alter sleep efficiency or number of awakenings , Stage 1 or REM sleep , or REM latency compared with baseline . Nefazodone was associated with significantly less change from baseline for sleep efficiency , number of awakenings , percentage of awake and movement time , percentage of REM and Stage 1 sleep , and REM latency compared with fluoxetine . Both fluoxetine- and nefazodone-treated patients also showed significant improvement in some clinician- and patient-rated sleep disturbance scores , but nefazodone-treated patients improved to a significantly greater extent than fluoxetine-treated patients in most measures . CONCLUSION While nefazodone and fluoxetine showed equivalent antidepressant efficacy , more objective , subjective , and clinician-rated measures of sleep disturbance were improved during treatment with nefazodone than with fluoxetine . These results suggest that antidepressant effects of medications can occur independently of drug-induced changes in objective , subjective , and clinician-rated measures of sleep . Further studies , including parallel placebo-controlled comparisons with nefazodone , are needed to further test this hypothesis BACKGROUND Controversy exists over antidepressant use in rapid-cycling bipolar disorder . AIMS Exploratory analysis of safety and efficacy of fluoxetine v. lithium monotherapy in individuals with rapid- v. non-rapid-cycling bipolar II disorder . METHOD R and omised , double-blind , placebo-controlled comparison of fluoxetine v. lithium monotherapy in patients initially stabilised on fluoxetine monotherapy ( trial registration NCT00044616 ) . RESULTS The proportion of participants with depressive relapse was similar between the rapid- and non-rapid-cycling groups ( P = 0.20 ) . The odds of relapse were similar between groups ( P = 0.36 ) . The hazard of relapse was similar between groups ( hazard ratio 0.87 , 95 % CI 0.40 - 1.91 ) . Change in mania rating scores was similar between groups ( P = 0.86 ) . There was no difference between groups in the rate of syndromal ( P = 0.27 ) or subsyndromal ( P = 0.82 ) hypomania . CONCLUSIONS Depressive relapse and treatment-emergent mood conversion episode rates were similar for lithium and fluoxetine monotherapy and placebo during long-term , relapse-prevention therapy of rapid- and non-rapid-cycling bipolar II disorder OBJECTIVE We investigated the frequency of quality assessment of r and omized controlled trials within systematic review s and the incorporation of the quality assessment in the analysis . STUDY DESIGN AND SETTING We included new systematic review s of at least five trials of therapeutic or preventive interventions that appeared in issue 2 , 2003 , of the Cochrane Data base of Systematic Review s. All systematic review s in the 2002 issues of the Annals of Internal Medicine , BMJ , JAMA , and Lancet were identified in Pubmed . All review s were assessed under unblinded conditions using preprinted extraction forms . RESULTS Trial quality was assessed in all Cochrane review s and most ( 74 % ) of the paper review s. When we excluded 11 paper review s that were also published as Cochrane review , the percentage remained similar ( 67 % ) . Fifty percent of all Cochrane review s and 61 % of all paper review s incorporated the results of the quality assessment in the analysis . CONCLUSION Half of the review s did not incorporate the results of the quality assessment in the analysis . Authors , peer- review ers , and editors should no longer focus exclusively on whether quality assessment has been performed but should also concentrate on incorporation of quality assessment s in the analysis of the systematic review & 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 & Anxious depression , defined as major depressive disorder ( MDD ) accompanied by high levels of anxiety , seems to be both common and difficult to treat , with antidepressant monotherapy often yielding modest results . We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression . We conducted a post-hoc analysis of an existing data set ( N=80 ) , from a 3-week , r and omized , double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD . The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement . Anxious depression status was not found to predict symptom improvement , or serve as a moderator of clinical improvement to cotherapy versus monotherapy . However , the advantage in remission rates in favor of cotherapy versus monotherapy was , numerically , much larger for patients with anxious depression ( 32.2 % ) than it was for patients without anxious MDD ( 9.7 % ) . The respective number needed to treat statistic for these two differences in response rates were , approximately , one in three for patients with anxious depression versus one in 10 for patients without anxious depression . The efficacy of fluoxetine-clonazepam cotherapy  compared with fluoxetine monotherapy  was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression The efficacy and safety of fluoxetine , a new antidepressant agent , were assessed in a double-blind , parallel , r and omized study of 44 out patients with major depressive disorder . Following a 1-week placebo period , patients were r and omly assigned to either fluoxetine or amitriptyline for a period of 5 weeks . The mean maintenance dosages were 55 mg/day for fluoxetine and 159 mg/day for amitriptyline . Both drugs were effective in relieving the symptoms of depression . The most frequently reported side effects were nausea and nervousness for fluoxetine , and dry mouth , dizziness , and drowsiness for amitriptyline Clinicians are faced with the challenge of keeping abreast of the rapidly growing clinical literature . One method that can help clinicians meet this challenge is the provision of synthesis ed evidence by such groups as the Cochrane Collaboration . The Cochrane Library contains the full text of Cochrane review s , which bring together information on controlled studies ( mostly r and omised controlled trials ) in a st and ard format . The first 1000 review s were prepared by early 2001 , and there are now more than 1600 available.1 The task of synthesis ing the clinical literature is a huge undertaking , and in this editorial we will use the number of studies in a typical Cochrane review to provide an estimate of the number of Cochrane review s that are needed to cover all trials currently in the Cochrane Central Register of Controlled Trials ( CENTRAL ) .2–3 CENTRAL is the main source used by Cochrane review ers to locate studies . It contains citations to more than 300 000 reports of studies , which may be eligible for inclusion in Cochrane review s. CENTRAL is reference-based rather than study -based , and therefore multiple references may be included for a single trial . We examined 1000 review s from the Cochrane Data base of Systematic Review s in Issue 1 , 2001 , of the Cochrane Library to determine the average number of studies , and references to the studies , included in a typical Cochrane review . Comparing this with an estimate for the number of relevant references in CENTRAL , it is possible to predict how many more Cochrane review s are needed to cover the healthcare research already in CENTRAL . Of the 1000 review s , 11 had been replaced by notices of withdrawal , leaving 989 complete review s. The included studies in these review s were h and counted by 1 author Background : Maintenance antidepressant ( AD ) medication is the most commonly used preventive strategy in a highly recurrent disease , i.e. depression . Little is known about the discontinuation of maintenance AD use and the association with recurrence in daily clinical practice . The purpose was to examine the discontinuation rate of maintenance AD in daily clinical practice in recurrently depressed patients and the associated risk of recurrence . Methods : Prospect ively AD maintenance medication and recurrence were examined in 172 euthymic patients with recurrent depression .  AD user profiles before recurrence ( nonusers , intermittent users , continuous users ) were examined and related to recurrence over a 2-year follow-up period . Results : Less than half of the patients ( 42 % ) used AD continuously . Taking into account the minimal required adequate used dosage ( ≧20 mg fluoxetine equivalent ) , only 26 % of the patients used AD as recommended by international guidelines . Despite continuous use of AD , 60.4 % relapsed in 2 years . This relapse rate was comparable to the rate of the intermittent users ( 63.6 % ) . In patients who stopped taking AD after remission and who received additional preventive CT , the recurrence rates were significantly lower than in non-AD-using patients treated with usual care ( 8 vs. 46 % ) . Conclusions : The majority of recurrently depressed patients treated with AD  discontinue maintenance AD therapy in daily primary and secondary clinical practice . AD seems to offer poor protection against relapse in this patient group . Patients who stopped using AD experienced less relapse , especially if they were treated with preventive CT . Alternative maintenance treatments ( including preventive cognitive therapy after discontinuation of AD ) should be studied in recurrently depressed patients with intermittent good remission , not only in secondary but also in primary care The effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients . The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment . However , that difference was no longer apparent during the remainder of the study . The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone Background —Acupuncture has recently been studied in assisted reproductive treatment ( ART ) although its role in reproductive medicine is still debated . Objectives —To determine the effectiveness of acupuncture  in the outcomes of ART . Search strategy —All reports which describe r and omised controlled trials of acupuncture in assisted conception were obtained through search es of the Menstrual Disorders and Subfertility Group Specialised Register , CENTRAL , Ovid MEDLINE ( 1996 to August 2007 ) , EMBASE ( 1980 to August 2007 ) , CINAHL ( Cumulative Index to Nursing & Allied Health Literature ) ( 1982 to August 2007 ) , AMED , National Research Register , Clinical Trials register ( www . clinical trials.gov ) , and the Chinese data base of clinical trials . Selection Criteria —R and omised controlled trials of acupuncture for couples who were undergoing ART comparing acupuncture treatment alone or acupuncture with concurrent ART versus no treatment , placebo or sham acupuncture plus ART for the treatment of primary and secondary infertility . Women with medical illness deemed contraindications for ART or acupuncture were excluded . Data Collection and Analysis —Sixteen r and omised controlled trials were identified that involved acupuncture and assisted conception . Thirteen trials were included in the review and three were excluded . Quality assessment and data extraction were performed independently by two review authors . © 2010 Elsevier Inc. All rights reserved . Corresponding author : Eric Manheimer , MS , Research associate , University of Maryl and School of Medicine , Center for Integrative Medicine East Hall , 520 W. Lombard Street Baltimore , MD 21201 , emanheimer@compmed.umm.edu , Telephone : 410 - 706 - 6169 , Fax : 410 - 706 - 6214 . * Both authors contributed equally to this work . The Cochrane Complementary Medicine Field is the group within the Cochrane Collaboration focused on facilitating the conduct of Cochrane systematic review s of CAM therapies . The CAM Field represents an international collaborative effort among research ers , clinicians , consumers , and CAM practitioners from nearly every continent . The Field ’s central office is located at the Center for Integrative Medicine , University of Maryl and School of Medicine , 520 W. Lombard St , Baltimore , MD 21201 . For more information , contact Eric Manheimer at : emanheimer@compmed.umm.edu . Publisher 's Discl aim er : This is a PDF file of an unedited manuscript that has been accepted for publication . As a service to our customers we are providing this early version of the manuscript . The manuscript will undergo copyediting , type setting , and review of the result ing proof before it is published in its final citable form . Please note that during the production process errors may be discovered which could affect the content , and all legal discl aim ers that apply to the journal pertain . NIH Public Mr. B , age 20 , has taken a semester leave from college because of gradually worsening depressed mood . Over the past 2 months he has lost interest in jogging and playing piano -- which he usually enjoys . He reports reduced libido , middle insomnia , loss of appetite , feeling as if his head is " full of cotton , " trouble concentrating , and waking in the morning with a sense of dread . His anxiety dissipates during the day , but he continues to feel sad and sometimes weepy , which is unusual for him . [ ILLUSTRATION OMITTED ] Mr. B reports feeling hopeless at times and has had vague thoughts about life being " not worth it if I continue to feel like this " but denies specific suicide plans . Your initial impression is that Mr. B is in the midst of a major depressive episode and that a selective serotonin reuptake inhibitor ( SSRI ) is indicated . As you finish taking his history , you run through your mind the pros and cons of the recommendation you will make to him . Do SSRIs raise or lower the risk for suicidal behavior in young adults such as Mr. B ? The answer is complicated and goes beyond an " either/or " question , as the FDA acknowledged in May 2007 when it : * extended the black-box warning of increased suicidality risk with antidepressants to cover adults age 18 to 24 as well as children and adolescents * included language in the warning about the benefits of treating depression and the suicide risk associated with untreated depression , given concerns about declining antidepressant prescriptions and rising suicides among youth . ( 1 ) To help you make informed decisions when treating depression in adults , this article review s the studies leading up to and following the FDA 's meta- analysis of antidepressant trial data in patients age 18 and older . Our goal is to provide a framework for clinical treatment of adults age 18 to 24 and those age [ greater than or equal to]25 . First hints of suicidality  SSRIs revolutionized depression treatment . From 1985 to 1999 , annual U.S. antidepressant prescriptions quadrupled , with SSRIs accounting for 70 % of the increase ( see " Antidepressants and suicide risk , 1985 to 2007 , " pages 36 - 37 ) . At the same time , the age-adjusted suicide rate : * dropped 22.5 % for women ( who account for twice as many antidepressant prescriptions as men ) * dropped 12.8 % for men ( without change in the rank order of suicide methods ) . ( 2 ) For many patients , increased antidepressant use improved treatment of major depressive and other antidepressant-responsive disorders . In 1990 , however , case reports suggested SSRIs might cause suicidal thoughts or behavior . ( 3 ) Hypothesized mechanisms included increased aggression ( 4 ) and akathisia . ( 5 ) An FDA review found no proof , and a meta- analysis of data from 17 double-blind , r and omized , controlled trials found no association between fluoxetine and suicidal thoughts or behavior . ( 6 ) The debate rekindled in June 2003 when the British Committee on Safety of Medicines warned against using paroxetine or venlafaxine in children . After conducting its own meta- analysis , the FDA in 2004 ordered a black-box warning about suicidality and the use of  antidepressants in children and adolescents ( Box ) . ( 7 ) After the pediatric ' black box . '  Antidepressant prescriptions for  children and adolescents declined in the years 2003 to 2004 , as did diagnosis of pediatric depression . ( 8 - 10 ) Antidepressant prescribing also showed signs of shifting from general practitioners to psychiatrists . ( 8) At the same time , the suicide rate  among youth age 60 ,  SSRI prescriptions continued to rise and suicide rates fell , ( 9 ) a pattern of change consistent with antidepressants protecting against suicide . An independent meta- analysis by Bridge et al ( 12 ) examined the pediatric trial data used in the FDA meta- analysis plus 7 additional studies . The selective noradrenaline re-uptake inhibitor reboxetine may have advantages over the selective serotonin re-uptake inhibitors fluoxetine and citalopram , in effects on sexual function and satisfaction . The effects of reboxetine and paroxetine on sexual function were compared by examining data from the UK centres in an international double-blind flexible-dose parallel-group multi-centre r and omized controlled trial of acute treatment of patients with DSM-IV major depression . Patients were r and omly assigned to receive reboxetine ( 4 mg b.d . ) or paroxetine ( 20 mg mane ) using a double-dummy technique to preserve the blind . The dosage could be increased at day 28 ( to reboxetine 4 mg mane , 6 mg nocte ; or paroxetine 20 mg b.d . ) . Antidepressant efficacy was assessed by the 21-item Hamilton Rating Scale for Depression ( HAM-D ) and Clinical Global Impression Scale for Severity ( CGI-S ) at all study visits , and the Clinical Global Impression of Improvement ( CGI-I ) at each visit after r and omization . Sexual function and satisfaction was assessed by visual analogue scale ( VAS ) items of the Rush Sexual Inventory completed at baseline and days 28 and 56 . There were no significant differences between groups in demographic or clinical features at baseline . There was a gradual reduction in severity of depressive symptoms  ( reboxetine , 14.3 ; paroxetine , 12.0 : observed case analysis ) , with no significant differences between groups . There were significant differences ( p 0.05 ) , with advantages for reboxetine , at Week 4 and Week 8 on the VAS item assessing ability to become sexually excited , and non-significant trends with advantages for reboxetine , in frequency of sexual thoughts at Week 4 ( p 0.05 ) and Week 8 ( p 0.08 ) ; and in desire to initiate sexual activity at Week 4 ( p 0.09 ) . Exclusion of patients who had ever experienced sexual dysfunction with any medication prior to participation in this study ( n 10 ) reduced the statistical significance of the findings , although there were still numerical advantages for reboxetine .  Sexual function and satisfaction in depressed patients improves during double-blind acute treatment with reboxetine or paroxetine , but this improvement is greater and more rapid with reboxetine 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 : While testosterone 's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature , no placebo-controlled trial selecting for depressive disorders and including a st and ard antidepressant has been conducted . Accordingly , this double-blind trial was design ed to determine whether testosterone , as well as fluoxetine , is superior to placebo for depression , fatigue , or both . Method : One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition depressive disorder entered the 8-week trial and were r and omized to testosterone ( up to 400 mg IM testosterone cypionate biweekly ) , fluoxetine ( up to 60 mg/d ) , or double placebo . Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue , the Hamilton Rating Scale for Depression , and the Chalder Fatigue Scale . Results : Ninety men completed the trial . In intention-to-treat analyses , mood response rates were 54 % , 47 % , and 44 % for fluoxetine , testosterone , and placebo , respectively . Among completers , mood response rates were 70 % , 57 % , and 53 % , respectively ; in neither analysis were differences between treatments statistically significant . In contrast , testosterone was superior to fluoxetine and placebo for completers regarding fatigue . In intention-to-treat analysis , response rates were 39 % , 56 % , and 42 % for fluoxetine , testosterone , and placebo , respectively , and for study completers , 41 % , 63 % , and 52 % , respectively , ( P < 0.05 ) , Conclusion : While over 50 % of patients treated with testosterone reported improved mood , this rate was not statistically superior to placebo . Thus , our findings do not support prescription of testosterone as a first-line treatment for depressive disorders  in HIV-positive men . However , if vali date d in additional studies , testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression Background Research suggests that depressive disorders exist on a continuum , with subthreshold symptoms causing considerable population burden and increasing individual risk of developing major depressive disorder . An alternative strategy to professional treatment of subthreshold depression is population promotion of effective self-help interventions that can be easily applied by an individual without professional guidance . The evidence for self-help interventions for depressive symptoms is review ed in the present work , with the aim of identifying promising interventions that could inform future health promotion campaigns or stimulate further research . Methods A literature search for r and omised controlled trials investigating self-help interventions for depressive disorders or depressive symptoms was performed using PubMed , PsycINFO and the Cochrane Data base of Systematic Review s. Reference lists and citations of included studies were also checked . Studies were grouped into those involving participants with depressive disorders or a high level of depressive symptoms , or non- clinical ly depressed participants not selected for depression . A number of exclusion criteria were applied , including trials with small sample sizes and where the intervention was adjunctive to antidepressants or psychotherapy . Results The majority of interventions search ed had no relevant evidence to review . Of the 38 interventions review ed , the ones with the best evidence of efficacy in depressive disorders were S-adenosylmethionine , St John 's wort , bibliotherapy , computerised interventions , distraction , relaxation training , exercise , pleasant activities , sleep deprivation , and light therapy . A number of other interventions showed promise but had received less research attention . Research in non- clinical sample s indicated immediate beneficial effects on depressed mood for distraction , exercise , humour , music , negative air ionisation , and singing ; while potential for helpful longer-term effects was found for autogenic training , light therapy , omega 3 fatty acids , pets , and prayer . Many of the trials were poor quality and may not generalise to self-help without professional guidance . Conclusion A number of self-help interventions have promising evidence for reducing subthreshold depressive symptoms . Other forms of evidence such as expert consensus may be more appropriate for interventions that are not feasible to evaluate in r and omised controlled trials . There needs to be evaluation of whether promotion to the public of effective self-help strategies for subthreshold depressive symptoms could delay or prevent onset of depressive illness , reduce functional impairment , and prevent progression to other undesirable outcomes such as harmful use of substances BACKGROUND Tricyclic antidepressants and serotonin reuptake inhibitors are considered to be equally effective , but differences may have been obscured by internally inconsistent measurement scales and inefficient statistical analyses . AIMS To test the hypothesis that escitalopram and nortriptyline differ in their effects on observed mood , cognitive and neurovegetative symptoms of depression . METHOD In a multicentre part-r and omised open-label design ( the Genome Based Therapeutic Drugs for Depression ( GENDEP ) study ) 811 adults with moderate to severe unipolar depression were allocated to flexible dosage escitalopram or nortriptyline for 12 weeks . The weekly Montgomery-Asberg Depression Rating Scale , Hamilton Rating Scale for Depression , and Beck Depression Inventory were scored both conventionally and in a more novel way according to dimensions of observed mood , cognitive symptoms and neurovegetative symptoms . RESULTS Mixed-effect linear regression showed no difference between escitalopram and nortriptyline on the three original scales , but symptom dimensions revealed drug-specific advantages . Observed mood and cognitive symptoms improved more with escitalopram than with nortriptyline .  Neurovegetative symptoms improved more with nortriptyline than with escitalopram . CONCLUSIONS The three symptom dimensions provided sensitive descriptors of differential antidepressant response and enabled identification of drug-specific effects Among a sample of 119 distressed high-utilizers of primary care , 45 % of patients evaluated by a psychiatrist as needing antidepressant treatment had been treated in the year before the examination . However , only 11 % of the patients needing antidepressants had received adequate dosage and duration of pharmacotherapy . In the year following the intervention , study patients whose physicians were advised regarding treatment during a psychiatric consultation  were more likely to receive  antidepressant medications  ( 52.7 % ) relative to a r and omized control group ( 36.1 % ) . However , the intervention did not significantly increase the provision of adequate antidepressant therapy  ( 37.1 % vs 27.9 % ) . Among study patients using antidepressants , patient characteristics did not differentiate patients who received adequate dosage and duration of antidepressant medications from those who did not . Analysis of data on the duration of antidepressant therapy for all health maintenance organization enrollees initiating use of antidepressants showed that only 20 % of patients who had been given prescriptions for first-generation antidepressants ( amitriptyline , imipramine , or doxepin ) filled four or more prescriptions in the following six months , compared to 34 % of patients who had prescriptions for newer antidepressants ( nortriptyline , desipramine , trazodone and fluoxetine ) . Experimental research evaluating whether these newer medications ( with more favorable side effect profiles ) improve adherence , and thereby patient outcome , is needed BACKGROUND One important approach to increasing recognition and treatment rates for depression in urban China is to identify persons with depression who have contact with primary health care services  , most of which are provided in the outpatient departments of general hospitals . We aim to assess the prevalence , risk factors and rates of recognition of depressive disorders in internal medicine outpatient departments of general hospitals . METHODS Out patients with depression among 5312 consecutive attendees at outpatient internal medicine departments of 23 r and omly selected general hospitals in Shenyang are identified by a two-stage screening process using the General Health Question naire and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders . Charts of subjects with DSM-IV depressive disorders are review ed to determine if treating clinicians made a diagnosis of depression or prescribed anti-depressant medications . RESULTS The current prevalence of any type of depressive disorder was 11.0 % ( 95 % CI : 10.1%-12.1 % ) ; and those of major depressive disorder , dysthymia , and depression not otherwise specified were 3.6 % ( 3.1%-4.2 % ) , 2.8 % ( 2.4%-3.4 % ) , and 4.1 % ( 3.5%-4.8 % ) respectively . Only 4.0 % ( 2.5%-6.1 % ) of the depressed patients were identified by the treating clinician and only 3.0 % ( 1.6%-4.9 % ) were provided with antidepressant medication . Older age , female gender , reporting religious beliefs , low educational level , low income level and widowhood were independently associated with the occurrence of depression . CONCLUSIONS The prevalence of depression in primary care setting s in urban China is lower than that reported in most western countries but the risk factors for depression are similar . The very low rates of recognition and treatment are related both to the low rates of care seeking for psychological problems and to the high-volume collective model of hospital-based primary care delivery . Increasing the recognition and treatment of depression in Chinese general hospitals will require changing the attitudes of patients and clinicians and , more importantly , altering the structure of care delivery 1 . The study evaluated the efficacy of amisulpride , fluoxetine and clomipramine at the beginning of the re-feeding phase of the treatment of restricting anorexia nervosa according to DSM-IV criteria . 2 . 13 patients , mean weight 37.61 kg + /- 9.80 SD , were treated with clomipramine at a mean dosage of 57.69 mg + /- 25.79 SD ; 10 patients , mean weight 40.90 kg + /- 6.98 SD , were treated with fluoxetine at a mean dosage of 28.00 mg + /- 10.32 SD ; 12 patients , mean weight 38.41 kg + /- 8.33 SD , were treated with amisulpride at a mean dosage of 50.00 mg + /- 0.00 SD . 3 . Clinical evaluation was carried out under single-blind condition at basal time and after three months by a structured clinical interview , the Eating Disorder Interview based on Long Interval Follow-up Evaluation ( LIFE II BEI ) . 4 . Patients treated with amisulpride showed a more significant increase ( p=0.016 ) of mean weight . Concerning weight phobia , body image disturbance and amenorrhoea , no significant difference result ed OBJECTIVE We developed a primary care/Internet-based intervention for adolescents at risk for depression ( CATCH-IT , Competent Adulthood Transition with Cognitive-behavioral , Humanistic and Interpersonal Training ) . This phase II clinical trial compares two forms of primary care provider ( PCP ) engagement ( motivational interview [ MI ] and brief advice [ BA ] ) for adolescents using the Internet program .  METHOD ADOLESCENTS SCREENING POSITIVE FOR DEPRESSION WERE RECRUITED FROM PRIMARY CARE PRACTICE S AND R AND OMLY ASSIGNED TO A VERSION OF THE INTERVENTION : PCP MI + Internet program or PCP BA + Internet program .  Between-group and within-group comparisons were conducted on depressive disorder outcome measures at baseline and one-year post-enrollment . Regression analyses examined factors predicting declines in depressed mood . RESULTS Both groups demonstrated significant within-group decreases in depressed mood , loneliness , and self-harm ideation . While no between-group differences were noted in depressed mood or depressive disorder measures at one-year , fewer participants in the MI group had experienced a depressive episode . Greater participant automatic negative thoughts and more favorable ratings of a component of the Internet-based training experience predicted declines in depressed mood at one-year . CONCLUSIONS A primary care/Internet-based intervention for depression prevention demonstrated sustained reductions in depressed mood , and , when coupled with motivational interviewing , reduction in the likelihood of being diagnosed with a depressive episode . This tool may help extend the services at the disposal of a primary care provider and can provide a bridge for adolescents at risk for depression prior to referral to mental health specialists 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 BACKGROUND In 2001 , the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments ( CANMAT ) partnered to produce evidence -based clinical guidelines for the treatment of depressive disorders .  A revision of these guidelines was undertaken by CANMAT in 2008 - 2009 to reflect advances in the field . This article , one of five in the series , review s new studies of psychotherapy in the acute and maintenance phase of MDD , including computer-based and telephone-delivered psychotherapy . METHODS The CANMAT guidelines are based on a question -answer format to enhance accessibility to clinicians . Evidence -based responses are based on up date d systematic review s of the literature and recommendations are grade d according to the Level of Evidence , using pre-defined criteria . Lines of Treatment are identified based on criteria that included evidence and expert clinical support . RESULTS Cognitive-Behavioural Therapy ( CBT ) and Interpersonal Therapy ( IPT ) continue to have the most evidence for efficacy , both in acute and maintenance phases of MDD , and have been studied in combination with antidepressants . CBT is well studied in conjunction with computer-delivered methods and bibliotherapy . Behavioural Activation and Cognitive-Behavioural Analysis System of Psychotherapy have significant evidence , but need replication . Newer psychotherapies including Acceptance and Commitment Therapy , Motivational Interviewing , and Mindfulness-Based Cognitive Therapy do not yet have significant evidence as acute treatments ; nor does psychodynamic therapy . LIMITATIONS Although many forms of psychotherapy have been studied , relatively few types have been evaluated for MDD in r and omized controlled trials . Evidence about the combination of different types of psychotherapy and antidepressant medication is also limited despite widespread use of these therapies concomitantly . CONCLUSIONS CBT and IPT are the only first-line treatment recommendations for acute MDD and remain highly recommended for maintenance . Both computer-based and telephone-delivered psychotherapy -- primarily studied with CBT and IPT -- are useful second-line recommendations . Where feasible , combined antidepressant and CBT or IPT are recommended as first-line treatments for acute MDD BACKGROUND One of the aims of the World Health Organization/Alcohol , Drug Abuse , and Mental Health Administration joint program on psychiatric diagnosis and classification is the development and st and ardization of diagnostic assessment instruments for use in clinical research worldwide . The International Personality Disorder Examination ( IPDE ) is a semistructured clinical interview compatible with the International Classification of Diseases , Tenth Revision , and the DMS-III-R classification systems . This is the first report of the results of a field trial to investigate the feasibility of using the IPDE to assess personality disorders worldwide . METHODS The IPDE was administered by 58 psychiatrists and clinical psychologists to 716 patients enrolled in clinical facilities at 14 participating centers in 11 countries in North America , Europe , Africa , and Asia . To determine interrater reliability , 141 of the IPDEs ( 20 % ) were independently rated by a silent observer . To determine temporal stability , 243 patients ( 34 % ) were reexamined after an average interval of 6 months . RESULTS The IPDE proved acceptable to clinicians and demonstrated an interrater reliability and temporal stability roughly similar to instruments used to diagnose the psychoses , mood , anxiety , and substance use disorders . CONCLUSION It is possible to assess personality disorders with reasonably good reliability in different nations , language s , and cultures using a semistructured clinical interview that experienced clinicians find relevant , meaningful , and user-friendly Diagnosis is a critical component of health care , and clinicians , policymakers , and patients routinely face a range of questions regarding diagnostic tests . They want to know whether testing improves outcome ; what test to use , purchase , or recommend in practice guidelines ; and how to interpret test results . Well- design ed  diagnostic test accuracy studies can help in making these decisions , provided that they transparently and fully report their participants , tests , methods , and results as facilitated , for example , by the STARD ( St and ards for Reporting of Diagnostic Accuracy ) statement ( 1 ) . That 25-item checklist was published in many journals and is now adopted by more than 200 scientific journals worldwide . As in other areas of science , systematic review s and meta- analysis of accuracy studies can be used to obtain more precise estimates when small studies addressing the same test and patients in the same setting are available . Review s can also be useful to establish whether and how scientific findings vary by particular subgroups , and may provide summary estimates with a stronger generalizability than estimates from a single study . Systematic review s may help identify the risk for bias that may be present in the original studies and can be used to address questions that were not directly considered in the primary studies , such as comparisons between tests . The Cochrane Collaboration is the largest international organization preparing , maintaining , and promoting systematic review s to help people make well-informed decisions about health care ( 2 ) . The Collaboration decided in 2003 to make preparations for including systematic review s of diagnostic test accuracy in their Cochrane Data base of Systematic Review s. To enable this , a working group ( Appendix ) . was formed to develop methodology , software , and a h and book The first diagnostic test accuracy review was published in the Cochrane Data base in October 2008 . In this paper , we review recent method ological developments concerning problem formulation , location of literature , quality assessment , and meta- analysis of diagnostic accuracy studies by using our experience from the work on the Cochrane H and book . The information presented here is based on the recent literature and up date s previously published guidelines by Irwig and colleagues ( 3 ) . Definition of the Objectives of the Review Diagnostic test accuracy refers to the ability of a test to distinguish between patients with disease ( or more generally , a specified target condition ) and those without . In a study of test accuracy , the results of the test under evaluation , the index test , are compared with those of the reference st and ard determined in the same patients . The reference st and ard is an agreed-on and accurate method for identifying patients who have the target condition . Test results are typically categorized as positive or negative for the target condition . By using such binary test outcomes , the accuracy is most often expressed as the test 's sensitivity ( the proportion of patients with positive results on the reference st and ard that are also positive on the index test ) and specificity ( the proportion of patients with negative results on the reference st and ard that are also negative on the index test ) . Other measures have been proposed and are in use ( 46 ) . It has long been recognized that test accuracy is not a fixed property of a test . It can vary between patient subgroups , with their spectrum of disease , with the clinical setting , or with the test interpreters and may depend on the results of previous testing . For this reason , inclusion of these elements in the study question is essential . In order to make a policy decision to promote use of a new index test , evidence is required that using the new test increases test accuracy over other testing options , including current practice , or that the new test has equivalent accuracy but offers other advantages ( 79 ) . As with the evaluation of interventions , systematic review s need to include comparative analyses between alternative testing strategies and should not focus solely on evaluating the performance of a test in isolation . In relation to the existing situation , 3 possible roles for a new test can be defined : replacement , triage , and add-on ( 7 ) . If a new test is to replace an existing test , then comparing the accuracy of both tests on the same population and with the same reference st and ard provides the most direct evidence . In triage , the new test is used before the existing test or testing pathway , and only patients with a particular result on the triage test continue the testing pathway . When a test is needed to rule out disease in patients who then need no further testing , a test that gives a minimal proportion of falsenegative results and thus a relatively high sensitivity should be used . Triage tests may be less accurate than existing ones , but they have other advantages , such as simplicity or low cost . A third possible role of a new test is add-on . The new test is then positioned after the existing testing pathway to identify false-positive or false-negative results after the existing pathway . The review should provide data to assess the incremental change in accuracy made by adding the new test . An example of a replacement question can be found in a systematic review of the diagnostic accuracy of urinary markers for primary bladder cancer ( 10 ) . Clinicians may use cytology to triage patients before they undergo invasive cystoscopy  , the reference st and ard for bladder cancer . Because cytology combines high specificity with low sensitivity ( 11 ) , the goal of the review was to identify a tumor marker with sufficient accuracy to either replace cytology or be used in addition to cytology . For a marker to replace cytology , it has to achieve equally high specificity with improved sensitivity . New markers that are sensitive but not specific may have roles as adjuncts to conventional testing . The review included studies in which the test under evaluation ( several different tumor markers and cytology ) was evaluated against cystoscopy or histopathology . Included studies compared 1 or more of the markers , cytology only , or a combination of markers and cytology . Although information on accuracy can help clinicians make decisions about tests , good diagnostic accuracy is a desirable but not sufficient condition for the effectiveness of a test ( 8) . To demonstrate that using a new test does more good than harm to patients tested , r and omized trials of test- and -treatment strategies and review s of such trials may be necessary . However , with the possible exception of screening , in most cases , such r and omized trials are not available and systematic review s of test accuracy may provide the most useful evidence available to guide clinical and health policy decision making and use as input for decision and cost-effectiveness analysis ( 12 ) . Identification and Selection of Studies Identifying test accuracy studies is more difficult than search ing for r and omized trials ( 13 ) . There is not a clear , unequivocal keyword or indexing term for an accuracy study in literature data bases comparable with the term r and omized , controlled trial . The Medical Subject Heading sensitivity and specificity may look suitable but is inconsistently applied in most electronic bibliographic data bases . Furthermore , data on diagnostic test accuracy may be hidden in studies that did not have test accuracy estimation as their primary objective . This complicates the efficient identification of diagnostic test accuracy studies in electronic data bases , such as MEDLINE . Until indexing systems properly code studies of test accuracy , search ing for them will remain challenging and may require additional manual search es , such as screening reference lists . In the development of a comprehensive search strategy , review authors can use search strings that refer to the test(s ) under evaluation , the target condition , and the patient description or a subset of these . For tests with a clear name that are used for a single purpose , search ing for publications in which those tests are mentioned may suffice . For other review s , adding the patient description may be necessary , although this is also often poorly indexed . A search strategy in MEDLINE should contain both Medical Subject Headings and free text words . A search strategy for articles about tests for bladder cancer , for example , should include as many synonyms for bladder cancer as possible in the search strategy , including neoplasm , carcinoma , transitional cell , and hematuria . Several method ological electronic search filters for diagnostic test accuracy studies have been developed , each attempting to restrict the search to articles that are most likely to be test accuracy studies ( 1316 ) . These filters rely on indexing terms for research methodology and text words used in reporting results , but they often miss relevant studies and are unlikely to decrease the number of articles one needs to screen . Therefore , they are not recommended for systematic review s ( 17 , 18 ) . The incremental value of search ing in language s other than English and in the gray literature has not yet been fully investigated . In systematic review s of intervention studies , publication bias is an important and well-studied form of bias in which the decision to report and publish studies is linked to their findings . For clinical trials , the magnitude and determinants of publication bias have been identified by tracing the publication history of cohorts of trials review ed by ethics committees and research boards ( 19 ) . A consistent observation has been that studies with significant results are more likely to be published than studies with nonsignificant findings ( 19 ) . Investigating publication bias for diagnostic tests is problematic , because many studies are done without ethical review or study registration ; therefore , identification of cohorts of studies from registration to final publication status We conducted a r and omized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy .  A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence . A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a " maintenance " dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed . Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy . We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication OBJECTIVE Treatment of bipolar depression with antidepressants is strongly debated on the basis of the method ologically poor and insufficient data supporting their use and the widely held belief that antidepressants can induce new episodes of abnormal mood elevation or accelerate the rate of cycling . The present study aim ed at identifying clinical risk factors for switch into hypomania , mania , or mixed states , within 8 weeks after introduction of an antidepressant or after increasing its dosage , in a prospect i ve , longitudinal design . METHOD 221 consecutive DSM-IV-TR depressed bipolar I and II disorder patients were treated with antidepressants , which were added to previously prescribed mood stabilizers and /or atypical antipsychotics . No patient was on antidepressant monotherapy .  The patients were enrolled from October 2005 through January 2010 . The primary outcome was the assessment of switch to mania or hypomania within 8 weeks after the introduction or dose increase of an antidepressant  . Both groups were compared with analysis of variance and χ² procedures . RESULTS Treatment-emergent affective switch was detected in 54 patients ( 24.4 % ) ( switch group ) while 167 patients ( 75.6 % ) ( nonswitch group ) did not experience a treatment-related switch . The main clinical differences significantly associated with the occurrence of an antidepressant-related switch , after performing logistic regression analysis , were higher rate of previous switches ( P < .001 ) in the switch versus the nonswitch group , lower rate of responses to antidepressants ( P < .001 ) in the switch versus the nonswitch group , and earlier age at onset ( P = .026 ) in the switch versus the nonswitch group . DISCUSSION Bipolar patients with an earlier age at onset and an illness course characterized by lower rate of response to antidepressants and higher rate of switches into mania or hypomania were found to be the ones with higher switch risk . Nevertheless , a greater number of previous antidepressant exposures was not associated with the occurrence of an antidepressant-associated switch . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01503489 The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a small therapeutic study : ( 1 ) the pathogenesis of panic disorder includes at least two identifiable components : a biological component represented by spontaneous ( unexpected ) panic attacks , and a cognitive component represented by situational attacks and especially by phobias ; ( 2 ) these components respond differently to treatment ; ( 3 ) many biological processes respond to an effective intervention in proportion to their deviance from " normal " prior to treatment ( " Law of Initial Value " ) ; and ( 4 ) the response of spontaneous panic attacks to an effective treatment conforms to that model . Previously , the authors reanalyzed an 8-week therapeutic study of panic disorder that included groups treated with  placebo  and with  imipramine ( 225 mg daily ) . The criteria of response were spontaneous panic attacks ( biological component ) , situational panic attacks ( both components ) , and agoraphobia ratings ( cognitive component ) . The analyses compared the regression lines for posttreatment status on pretreatment status in the imipramine and placebo groups . The effect of imipramine on spontaneous panic attacks fitted the hypothesized model : the pre-post slope in the placebo group was approximately 1 ( 45 degrees ) , whereas the slope in the imipramine group was approximately 0 . There was no significant difference in pre-post slopes between the imipramine and placebo groups for situational panic attacks or agoraphobia ratings . For this report , the authors applied the same approach to another larger data set from a study using a similar design , but a different antidepressant . In this multicenter , double-blind study , patients with panic disorder were r and omly assigned to receive 10 weeks of treatment with  placebo ( N = 78 ) or fluoxetine 10 mg ( N = 84 ) or 20 mg ( N = 81 ) daily . Spontaneous and situational panic attacks were registered in a daily diary , and agoraphobia was rated at each visit . Using baseline and endpoint data , fluoxetine had a statistically significant , dose-dependent , suppressive effect on spontaneous panic attacks , as measured by the pre-post slopes in the three treatment groups . The placebo group showed some response ( slope = 0.69 ) . There were no significant drug effects on situational panic attacks . On ratings of agoraphobia , the slopes in the placebo and the fluoxetine 20 mg groups did not differ , but the slope in the fluoxetine 10 mg group was significantly less than that in the placebo group , suggesting a therapeutic drug effect on agoraphobia only at the lower dose . These results are consistent with the stated hypotheses . They suggest that the therapeutic effects of antidepressants on panic disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings . Implication s of these results for concepts of pathogenesis , clinical practice , and therapeutic research regarding panic disorder are discussed 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 Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine . METHOD A r and omized , single-blind , parallel-group study of 10 weeks ' duration comparing the efficacy of sertraline , 50 mg/day ; sertraline , 100 mg/day ; and fluoxetine , 20 mg/day , was conducted in 44 psychiatric out patients with DSM-IV unipolar major depressive disorder . Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission . Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impressions-Improvement scale ( CGI-I ) , with scores of < or = 7 on the HAM-D and < or = 2 on the CGI-I representing a positive treatment response , i.e. , remission . RESULTS At 4 weeks , significant differences in rate of positive treatment response were noted , with 0 % for sertraline , 50 mg ; 46 % for sertraline , 100 mg ; and 31 % for fluoxetine , 20 mg ( p = .023 ) . At 6 weeks , positive treatment response rates were 21 % , 43 % , and 31 % for subjects taking 50 mg of sertraline , those taking 100 mg of sertraline , and those taking 20 mg of fluoxetine , respectively , with treatment groups no longer differing significantly from each other . In subjects for whom antidepressant dose was doubled at week 6 , response rates at week 10 ( 4 weeks on increased dose ) were 40 % for sertraline , 100 mg ; 43 % for sertraline , 200 mg ; and 55 % for fluoxetine , 40 mg . CONCLUSION Subjects taking sertraline , 100 mg , and  fluoxetine , 20 mg , demonstrated an earlier treatment response compared with subjects taking sertraline , 50 mg . For patients without a positive response at 6 weeks , an increased antidepressant dose result ed in remission for a substantial proportion of patients when assessed 4 weeks later BACKGROUND Previous reports have suggested that lamotrigine is effective as an antidepressant augmentation agent in patients with treatment-resistant unipolar depression . This study is the largest double-blind placebo-controlled study conducted to date of lamotrigine in this role . METHOD In this multicenter trial , conducted at 19 sites , patients aged 18 - 65 years with a DSM-IV/ICD-10 diagnosis of unipolar , nonpsychotic major depressive disorder ( confirmed by the Mini-International Neuropsychiatric Interview ) who had failed at least 1 adequate trial of an antidepressant ( N = 183 ) were first treated for 8 weeks with open-label paroxetine or paroxetine controlled-release in dosages up to 50 mg/d or 62.5 mg/d , respectively . Individuals with a 17-item Hamilton Depression Rating Scale ( HDRS-17 ) score ≥ 15 ( n = 96 ) were then r and omized on a double-blind basis to receive either placebo or lamotrigine in dosages titrated upward to a maximum of 400 mg/d for 10 weeks . Sixty-five patients completed the study . The primary outcome measure was the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the main secondary outcome measures were the HDRS-17 and Clinical Global Impressions-Severity of Illness ( CGI-S ) and Clinical Global Impressions-Improvement ( CGI-I ) ratings . Data were collected from 2003 to 2006 . RESULTS Results of the primary efficacy analysis of the r and omized patients using the MADRS , HDRS-17 , CGI-S , and CGI-I did not demonstrate a statistically significant difference between lamotrigine and placebo groups , although some secondary analyses were suggestive of efficacy , particularly in those patients who completed the study ( completer analysis ) and in more severely ill patients ( HDRS-17 ≥ 25 ) . CONCLUSIONS This add-on study of patients with treatment-resistant depression failed to detect a statistically significant difference between lamotrigine and placebo given for 10 weeks . However , post hoc analyses suggest that future studies of lamotrigine 's efficacy might focus on specific subgroups with depression . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00901407 BACKGROUND In 2001 , the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments ( CANMAT ) partnered to produce evidence -based clinical guidelines for the treatment of depressive disorders . A revision of these guidelines was undertaken by CANMAT in 2008 - 2009 to reflect advances in the field . There is renewed interest in refined approaches to brain stimulation , particularly for treatment resistant major depressive disorder ( MDD ) . METHODS The CANMAT guidelines are based on a question -answer format to enhance accessibility to clinicians . An evidence -based format was used with up date d systematic review s of the literature and recommendations were grade d according to Level of Evidence using pre-defined criteria . Lines of Treatment were identified based on criteria that included evidence and expert clinical support . This section on " Neurostimulation Therapies " is one of 5 guidelines articles . RESULTS Among the four forms of neurostimulation review ed in this section , electroconvulsive therapy ( ECT ) has the most extensive evidence , spanning seven decades . Repetitive transcranial magnetic ( rTMS ) and vagus nerve stimulation ( VNS ) have been approved to treat depressed adults in both Canada and the United States with a much smaller evidence base . There is also emerging evidence that  deep brain stimulation ( DBS )  is effective for otherwise treatment resistant depression , but this is an investigational approach in 2009 . LIMITATIONS Compared to other modalities for the treatment of MDD , the data based is limited by the relatively small numbers of r and omized controlled trials ( RCTs ) and small sample sizes . CONCLUSIONS There is most evidence to support ECT as a first-line treatment under specific circumstances and rTMS as a second-line treatment . Evidence to support VNS is less robust and DBS remains an investigational treatment Background Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase . Some evidence has been reported for interventions for fatigue during active treatment . However , to date , there is no systematic review on psychological interventions for fatigue after the completion of curative treatment for cancer . This is a protocol for a systematic review that aims to evaluate the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors . This systematic review protocol was registered with the International Prospect i ve Register of Systematic Review s ( PROSPERO ) data base . Methods / design We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ; The Cochrane Library ) , PubMed , MEDLINE , EMBASE , CINAHL , PsycINFO , and relevant sources of grey literature . R and omised controlled trials ( RCTs ) which have evaluated psychological interventions in adult cancer patients after the completion of treatment , with fatigue as an outcome measure , will be included . Two review authors will independently extract data from the selected studies and assess the method ological quality using the Cochrane Collaboration Risk of Bias Tool . Discussion Most existing evidence on cancer-related fatigue is from those in active cancer treatment . This systematic review and meta- analysis will build upon previous evaluations of psychological interventions in people during and after cancer treatment . With the growing need for stage-specific research in cancer , this review seeks to highlight a gap in current practice and to strengthen the evidence base of r and omised controlled trials in the area . Systematic review registration PROSPERO CRD42014015219 Introduction Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) , the main forms of inflammatory bowel disease ( IBD ) , are chronic , progressive and disabling disorders of the gastrointestinal tract . Although data from r and omised controlled trials ( RCTs ) provide the foundation of evidence that vali date s medical therapy for IBD , considerable heterogeneity exists in the measured outcomes used in these studies . Furthermore , in recent years , there has been a paradigm shift in IBD treatment targets , moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance , inflammatory biomarkers and histological and radiographic end points . The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development . Accordingly , there exists a need to harmonise measures used in clinical trials through the development of a core outcome set ( COS ) . Methods and analysis The development of an IBD-specific COS includes four steps . First , a systematic literature review is performed to identify outcomes previously used in IBD RCTs . Second , semistructured qualitative interviews are conducted with key stakeholders , including patients , clinicians , research ers , pharmaceutical industry representatives , healthcare payers and regulators to identify additional outcomes of importance . Using the outcomes generated from literature review and stakeholder interviews , an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS . Finally , a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials . Ethics and dissemination Given that over 30 novel therapeutic compounds are in development for IBD treatment , the design of robust clinical trials measuring relevant and st and ardised outcomes is crucial . St and ardising outcomes through a COS will reduce heterogeneity in trial reporting , facilitate valid comparisons of new therapies and improve clinical trial quality OBJECTIVE This study assesses the efficacy and tolerability of fluoxetine in the acute treatment of child and adolescent obsessive-compulsive disorder ( OCD ) during a 13-week , double-blind , placebo-controlled study . METHOD Eligible patients aged 7 to 17 ( N = 103 ) were r and omized at a ratio of 2:1 to receive either fluoxetine or placebo . Dosing was initiated at 10 mg daily for 2 weeks , then increased to 20 mg daily . After 4 weeks of treatment , and again after 7 weeks of treatment , non-responders could have their dosage increased by 20 mg daily , for a maximum possible dosage of 60 mg daily . Primary measure of efficacy was improvement in OCD symptoms as measured by the Children 's Yale-Brown Obsessive Compulsive Scale ( CY-BOCS ) . All analyses were intent-to-treat . RESULTS Fluoxetine was associated with significantly greater improvement in OCD as assessed by the CY-BOCS ( p = .026 ) and other measures than was placebo . Fluoxetine was well tolerated and had a rate of discontinuation for adverse events similar to that of placebo ( p = 1.00 ) . CONCLUSIONS Fluoxetine 20 to 60 mg daily was effective and well tolerated for treatment of OCD in this pediatric population Context Does augmentation with an atypical antipsychotic improve symptoms in patients with major depression that is suboptimally responsive to antidepressant monotherapy ? Contribution This double-blind r and omized trial found that 6 weeks of treatment with risperidone improved symptoms more than placebo in 274 adults with major depression that was suboptimally responsive to antidepressant monotherapy . Risperidone , compared with placebo , result ed in more remissions ( 25 % vs. 11 % ) , as well as more cases of somnolence ( 5 % vs. 2 % ) and dry mouth ( 5 % vs. 1 % ) . Caution The trial duration was short , and 19 % of risperidone recipients did not complete treatment . Implication Risperidone augmentation may improve symptoms in some patients with suboptimal response to antidepressant monotherapy . The Editors Major depressive disorder is the leading cause of disability worldwide ( 1 ) , affecting nearly 121 million people . It is associated with increased overall mortality ( 2 , 3 ) ; premature cardiovascular-related death ( 4 , 5 ) ; and morbidity , including disability , lost productivity , and decreased wages , compared with individuals without depression ( 6 ) . Selective serotonin reuptake inhibitors ( SSRIs ) and serotoninnorepinephrine reuptake inhibitors are generally considered first-line treatments for depression . Despite a sufficient dose and duration of antidepressant treatment , symptoms do not resolve in 30 % to 40 % of patients with major depressive disorder ( 710 ) . Remission , defined as the virtual absence of depressive symptoms , is important because it is associated with improved patient prognosis and functioning relative to response ( generally defined as 50 % reduction in symptoms ) ( 11 , 12 ) . In an effort to improve the therapeutic efficacy of antidepressant monotherapy , several pharmacologic strategies to modulate different or additional neurotransmitters ( 1315 ) are commonly used , despite a paucity of evidence from r and omized clinical trials . These strategies include switching monotherapy within ( 10 , 1618 ) or between antidepressant classes ( 10 , 1921 ) , combination regimens consisting of 2 antidepressants ( 2226 ) , and augmentation of antidepressants with nonst and ard treatmentsfor example , thyroid hormone ( 27 ) ; S-adenosyl-l-methionine ( 28 ) ; lithium ( 29 ) ; cyclooxygenase-2 inhibitors ( 30 ) ; or an atypical antipsychotic ( 3133 ) , such as risperidone . Findings of several open-label studies ( 3135 ) suggest that atypical antipsychotic augmentation provides benefit in major depressive disorder that is suboptimally responsive to antidepressant monotherapy . Risperidone , whose activity includes blockade of certain serotonin and dopamine receptors , is considered an atypical antipsychotic . It is approved in the United States for treatment of bipolar mania and schizophrenia and in other countries for additional uses . The efficacy of risperidone has also been studied for various psychoses and behavioral disorders , including treatment-resistant depression and anxiety spectrum disorders ( 34 , 3639 ) . We hypothesized that low-dose risperidone augmentation would reduce symptoms of major depressive disorder , enhance clinical response and remission rates , and reduce disability and improve quality of life compared with continued antidepressant monotherapy . Preliminary data suggest that persons with a confirmed suboptimal response to previous treatment may respond to risperidone augmentation within 4 to 6 weeks ( 38 ) . We therefore conducted a large , multicenter , double-blind , placebo-controlled trial to assess the clinical efficacy of risperidone augmentation from the clinician and patient perspectives and to evaluate tolerability in patients with major depressive disorder who continue to experience symptoms despite an adequate trial of st and ard antidepressants . Methods Design Consenting persons entered a 4-week prospect i ve open-label run-in period during which they received their current antidepressant monotherapy at the dosages recommended in product labeling , so that we could confirm an insufficient response to st and ard monotherapy . The run-in period was followed by a 6-week double-blind treatment phase ; during this phase , patients who continued to experience depressive symptoms , defined as a Clinical Global ImpressionSeverity of illness ( CGI-S ) score of 4 or greater and a Carroll Depression Scale ( 40 ) score of 20 or greater , were r and omly assigned to receive risperidone augmentation therapy or placebo . A 4-week follow-up phase of open-label risperidone augmentation therapy was available to participants who completed at least 4 weeks of double-blind treatment ( results not shown ) . Setting and Participants Out patients 18 to 65 years of age who had received antidepressant monotherapy for at least 4 weeks and met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( 41 ) , criteria for unremitting major depressive disorder ( single or recurrent episodes ) and a CGI-S score of 4 or more ( 42 ) at the start of both the open-label and double-blind phases were eligible . The CGI-S is scored on a scale of increasing intensity from 1 to 7 , with 4 representing moderate illness . We recruited participants by using various methods , including media advertisements , and enrolled persons from 75 public and private primary care ( n= 41 ) and psychiatric ( n= 34 ) centers in the United States between 19 October 2004 and 17 November 2005 . Ethical approval was obtained from the institutional review board of each site , and written informed consent was obtained from all patients . Exclusion criteria were pregnancy ; serious suicidal risk or serious medical or neurologic illness ; active substance or alcohol use disorders ; or current treatment with a tricyclic antidepressant , monoamine oxidase inhibitor , mood stabilizer , antiepileptic , or a central ly acting agent for attention deficit disorder/attention deficit hyperactivity disorder or narcolepsy . R and omization and Interventions Patients who were eligible for r and omization continued their st and ard antidepressant regimen and dosage and were assigned to receive risperidone or placebo . Tablets were identical in appearance . The investigators , study staff , and patients were blinded to the treatment assignment . The r and omization code was central ly generated and administered by a telephone interactive voice response system , was stratified by antidepressant class ( SSRI or non-SSRI ) and center , and occurred in r and om permuted blocks . An independent statistician provided the r and omization codes . The dosing schedule was 0.25 mg for the first 3 days , 0.5 mg on days 4 to 15 , and 1.0 mg on days 16 to 28 . On day 29 , patients with insufficient treatment response in the opinion of the investigator could continue augmentation at the current dosage , have the dosage increased to 2 mg/d , or discontinue double-blind treatment . Concomitant medications were allowed as necessary for medical conditions . Sedative agents ( zolpidem , 2.5 to 10 mg/d , or zaleplon , 5 to 20 mg/d , as needed ) were allowed for insomnia . During double-blind treatment , benztropine mesylate was permitted as needed for potential treatment-emergent motor effects . Measurements and Outcomes At each visit ( end of the open-label phase and weeks 1 , 2 , 4 , and 6 ) , trained personnel administered the grid version of the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) ( 43 , 44 ) and the CGI-S ( 42 ) , both clinician-rated instruments . Scores on the HRSD-17 range from 0 to 52 ; higher scores indicate more severe depression . Patients also independently rated their response by using the telephone interactive voice response system at baseline and weekly thereafter . Other patient-reported outcomes were scores on 3 vali date d instruments : the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) ( 45 ) , the Patient Global Improvement Scale ( 7-point rating from 1 [ very much improved ] to 7 [ very much worse ] ) , and the Sheehan Disability Scale ( SDS ) . Change in HRSD-17 total score from baseline to study end was the a priori primary efficacy measure . Response ( 50 % reduction in HRSD-17 total score from baseline ) and remission ( HRSD-17 total score 7 ) were assessed at each time point . Secondary measures were changes in the CGI-S , Q-LES-Q , SDS , and Patient Global Improvement Scale scores . Follow-up Patients underwent physical examination , including assessment of vital signs , at regular intervals . Research staff maintained records of trial medication and assessed treatment compliance by matching doses taken with the number of treatment days . To assess adverse effects , patients were interviewed at each study visit with open-ended questions about potential adverse events ; spontaneous reports were also taken into account . All adverse events were recorded , and the investigator assessed each event for severity and relationship to the study drug ( probable , possible , not related ) . Statistical Analysis A sample of 116 patients per group was anticipated to have 90 % power to detect an arbitrary difference in change in mean HRSD-17 total score of 3.0 units , assuming a common SD of 7.0 using a 2-group t test and a 2-sided significance level of 0.05 . We also assumed that approximately 30 % of the participants would not complete double-blind treatment and planned for 332 persons to undergo r and omization . We further assumed that during the open-label run-in phase , 30 % of participants would discontinue the study and 20 % would respond to st and ard antidepressant treatment and therefore be ineligible for r and omization ; thus , we sought 592 persons for the open-label run-in phase . All analyses were performed by using SAS , version 8.2 ( SAS Institute , Cary , North Carolina ) , and statistical analysis personnel were blinded to patient group assignment . Baseline patient characteristics were summarized by using descriptive statistics . Efficacy and safety analyses were based on the intention-to-treat population ( that is , all persons who underwent r and omization and received at least 1 dose of medication in the double-blind phase ) . OBJECTIVE Minor depressive disorder is both common and associated with significant psychosocial impairment . This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder . METHOD One hundred sixty-two patients with minor depressive disorder were r and omly assigned to receive fluoxetine or placebo in a 12-week , double-blind study ; 73 % ( 59 of 81 ) of the patients in each treatment group completed the study . Patients were evaluated weekly with st and ard depression rating instruments and measures of psychosocial impairment . Hypotheses were tested by last-observation-carried-forward analysis of variance ( ANOVA ) and confirmed by mixed ( r and om-effects ) regression analysis . RESULTS At baseline , minor depressive disorder patients were mildly to moderately depressed , with a corresponding degree of functional impairment . Over 12 weeks of treatment , both ANOVA and mixed regression showed fluoxetine to be superior to placebo as indicated by significantly greater improvement of fluoxetine-treated patients in scores on the 30-item clinician-rated Inventory of Depressive Symptomatology , the 17-item and 21-item Hamilton Depression Rating Scale , the Beck Depression Inventory , and the Clinical Global Impression severity scale . Improvement in Global Assessment of Functioning Scale score was significantly greater for the fluoxetine group in mixed regression analysis only . Patients in both treatment groups reported a similar number and severity of adverse events during the 12-week treatment period . CONCLUSIONS Clinicians frequently encounter minor depressive disorder either as a prodromal or residual phase of illness in major depressive disorder or as de novo minor depressive disorder episodes . Fluoxetine is significantly superior to placebo in reducing minor depressive disorder symptoms within a 12-week period . Improvement in psychosocial function with fluoxetine may take longer than 12 weeks Rationale Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder . Little is known about fluoxetine ’s influence on mood changes after quitting smoking , which often resemble sub- clinical depression . Objectives The present study , a re- analysis of previously published data ( Niaura et al. 2002 ) , examined fluoxetine ’s effect on changes in negative and positive affect following quitting smoking . Methods Adult smokers ( n=175 ) without clinical ly significant depression were r and omized on a double-blind basis to receive fluoxetine hydrochloride ( 30 or 60 mg daily ) or placebo for 10 weeks in combination with cognitive-behavioral therapy ( CBT ) for smoking cessation . We postulated that fluoxetine would beneficially influence post-cessation changes in positive and negative affect . Results Mood change across treatment was analyzed using mixed linear modeling controlling for initial level of nicotine dependence , plasma fluoxetine metabolites , and change in cotinine ( a nicotine metabolite ) at each visit . Relative to placebo , those on 60 mg fluoxetine experienced an elevation in positive affect that increased across time [ t(526)=2.50 , P=0.01 ] , and a reduction in negative affect that returned to baseline across time [ t(524)=2.26 , P=0.02 ] . There were no differences between 30 mg and placebo on changes in positive or negative affect . Conclusions Results indicate that 60 mg of fluoxetine improves both positive and negative mood states after quitting smoking and that diminished positive affect may be an overlooked affective response to smoking cessation OBJECTIVE Many cl aims have been made for superior compliance with selective serotonin reuptake inhibitors ( SSRIs ) compared with tricyclic antidepressants , but to date meta-analyses have not confirmed reduced dropouts in r and omized controlled trials . The authors used a r and omized study design to evaluate differential compliance with antidepressant medications in a primary care setting . METHOD A total of 152 patients treated in 10 primary care practice s in the United Kingdom were included in a r and omized , open-label , parallel-group study of fluoxetine and dothiepin at therapeutic doses for 12 weeks . Compliance was assessed by using pill count , patient question naires , and the Medication Event Monitoring System . RESULTS The level of compliance with fluoxetine was numerically higher than the level of compliance with dothiepin on all three primary outcome measures , although the differences were not significant . In a secondary analysis using data from the Medication Event Monitoring System , both a survival analysis for length of time without a gap in medicine taking and a derived compliance index showed a significant advantage to fluoxetine . Patients in the fluoxetine group reported superior response on the health transition scale of the 36-item Short-Form Health Survey Question naire and numerically greater improvement on the Hamilton Depression Rating Scale . In both treatment arms patients with a superior compliance index were more likely to have improved in Hamilton depression scale scores by the last study visit . CONCLUSIONS This study supports recent meta-analyses of SSRIs versus tricyclic antidepressants in finding no significant differences in crude indices of compliance between fluoxetine and dothiepin , despite marked differences in side effect profile and dose regimen . However , both a survival analysis and a new measure that takes account of prolonged periods of noncompliance distinguished between the treatments and was associated with improvement in both groups Objective : For children with croup controversy remains over dosage and time to onset of action of oral steroids . The Cochrane Collaboration and other review s have suggested 0.6 mg/kg dexamethasone be used ( despite some evidence that 0.15 mg/kg is effective ) with no expectation of benefit before 4–6 h. This r and omized double‐blinded clinical trial examines whether 0.15 mg/kg dexamethasone works by 30 min Background and Objectives .—Antidepressants are often used to treat chronic daily headache disorders such as transformed migraine , in part because of the high prevalence of associated mood disorder . We conducted this study to evaluate the efficacy and tolerability of combined treatment with amitriptyline and fluoxetine compared with amitriptyline alone for chronic daily headache due to transformed migraine The efficacy and tolerability of moclobemide ( 300 or 600 mg daily ) and fluoxetine ( 20 or 40 mg daily ) were compared in a 6-week , double-blind study of 25 in patients and 24 out patients who had major depressive episodes without psychotic features ( DSM-III-R ) . Although the clinical results of this study suggest better efficacy with moclobemide and better tolerability with fluoxetine , a statistically significant difference between treatment groups was noted only with respect to Clinical Global Impressions recorded after 10 days of therapy ; these were significantly better in the moclobemide group . A daily dosage of 300 mg of moclobemide and 20 mg of fluoxetine would thus appear to be comparable both in antidepressant efficacy and tolerability During an open clinical trial , 51 schizophrenic patients were treated with  Penfluirdol  , 34 for 1 year and 17 for a shorter time . The mean dosage of Penfluirdol was 22 up to 28 mg per week . Assessment s were made on days 0 , 14 , 28 , 56 , 90 , 180 , 270 , and 365 using the AMP system and the EPRS scale of Simpson and Angus . The symptomatology was mainly reduced during the first 3 months of treatment and remained afterwards relative unchanged . Penfluridol showed a good antipsychotic effect on productive schizophrenic symptoms ( thought disorders and paranoid symptoms , autism and schizophrenic affective disorders ) . The dosage used showed only a slight sedative effect and was well tolerated concerning autonomic and extrapyramidal side-effects OBJECTIVE Depressive disorders cause substantial work impairment that can lead to disability compensation . The authors compared treatment received for depression preceding disability pension between 2 nationally representative sample s with a 10-year interval . METHOD The medical statements for 2 r and om sample s drawn from the Finnish national disability pension registers , representing population s granted a disability pension for DSM-III-R major depression during a 12-month period from October 1993 through September 1994 ( N = 277 ) and for ICD-10 depressive disorders ( F32-F33 ) from October 2003 through September 2004 ( N = 265 ) were examined . The proportions of persons receiving weekly psychotherapy , antidepressants , adequate antidepressant dosage , sequential antidepressant trials , lithium augmentation , and electroconvulsive therapy ( ECT ) were compared . RESULTS No significant differences emerged between the 2 sample s , except for the adequacy of antidepressant dosage . Few subjects in either of the sample s ( 8.7 % for 1993 - 1994 vs. 10.6 % for 2003 - 2004 , p = .45 ) had received weekly psychotherapy .  Most had received antidepressants ( 87.4 % vs. 85.6 % , p = .55 ) with increasingly adequate dosage ( 75.6 % vs. 85.0 % , p = .02 ) , but only a minority had received sequential antidepressant trials ( 39.5 % vs. 44.5 % , p = .24 ) .  Lithium augmentation and ECT  were rare ( 1.1 % vs. 1.5 % , p = .66 and 4.0 % vs. 1.5 % , p = .08 , respectively ) . Even in 2003 - 2004 , over half of the subjects were granted a disability pension without sequential antidepressant trials . CONCLUSION This nationally representative study indicates that , despite an increased antidepressant use and improved practice guidelines for depression , a considerable proportion of the people granted long-term compensation for depression seem to be suboptimally treated . Given the enormous costs of the disability , attention to the quality of treatment provided for depression is warranted before long-term disability compensations are granted Objective : The aims of the paper are to determine whether nutritional counselling is associated with an improvement in bulimic symptomatology , whether this improvement is maintained during post-treatment follow-up , and whether the addition of fluoxetine 3 × 20 mg/day confers additional benefit . Method : Psychological , pharmacological and combined psychopharmacological treatments of bulimia nervosa were review ed briefly . Sixty-seven patients referred to specialist eating disorder services who fulfilled strict diagnostic criteria were treated with intensive nutritional counselling and r and omly assigned to either fluoxetine 3 × 20 mg/day or placebo . After a 1-week ‘ wash-out ’ , active treatment was given over 8 weeks , followed by post-treatment interviews at 12 and 20 weeks . Results : Both groups of patients improved significantly during treatment . In some respects , the fluoxetine group did slightly better as demonstrated by the items ‘ restraint ’ , ‘ weight concern ’ and ‘ shape concern ’ ( p<0.05 vs p<0.0001 ) on the Eating Disorder Examination ( EDE ) . Fluoxetine patients decreased their energy intake and lost a modest amount of weight . They went on to regain weight during the follow-up period , returning to levels higher than they were initially . These patients also appeared more likely to have a recurrence of symptoms , as shown by the fall in percentage of binge-free patients and by changes in the EDE . Conclusion : Nutritional counselling is an effective means of treating bulimia nervosa , with improvement maintained up to 3 months follow-up . The addition of fluoxetine may confer some benefit during active treatment , but its discontinuation may contribute to a higher rate of recurrence of symptoms post treatment . Of course , this study can not be extrapolated to the efficacy of fluoxetine when used as the only form of treatment in patients for whom intensive nutritional counselling or other structured psychological programs are not available BACKGROUND Cancer treatment-related fatigue ( CRF ) is a common side effect of cancer treatment . A problem identified in most review s of CRF is lack of sound approaches to measurement that are congruent with the conceptualization of CRF as a self-perceived state . The diversity of instruments available to measure fatigue and the lack of comprehensive testing of several promising instruments with cancer patients undergoing treatment provided the rationale for this study . The purpose of this article is to report the results of psychometric testing of several fatigue instruments in patients undergoing cancer treatment . OBJECTIVES The aims of this study were to determine the reliability , validity , and responsiveness of each instrument and to determine the ability of each instrument to capture CRF . METHODS Existing fatigue instruments with published psychometric information that indicated suitability for further testing were selected and included the Profile of Mood States Short Form fatigue subscale ( F_POMS-sf ) ,  Multidimensional Assessment of Fatigue ( MAF ) ,  Lee Fatigue Scale ( LFS ) , and the  Multidimensional Fatigue Inventory ( MFI ) . Data were collected at a university-based clinical cancer center and a freest and ing comprehensive cancer center . Subjects completed all study instruments , which were presented in r and om order , at a time when CRF was expected to be high and again when it was expected to be low . A subset of subjects completed the instruments within 48 hours of one of the data collection points when CRF was expected to be relatively unchanged to provide stability data . RESULTS Reliability estimates using Cronbach 's alpha indicated that all instruments examined had good internal consistency . Test-retest correlations showed good stability for total scores on all the instruments , but some subscales of the LFS and MFI had marginal stability . Factor analysis of all instruments indicated that only the LFS and the F_POMS-sf fully supported their construct validity . All of the instruments showed responsiveness to changes in CRF related to treatment . CONCLUSIONS The results of the study provide research ers and clinicians with detailed comparisons of the performance of established fatigue measures in cancer patients undergoing treatment to use when selecting measures of CRF The efficacy and tolerability of moclobemide ( 300–600 mg daily ) and fluoxetine ( 20–40 mg daily ) were compared in a 6-week , double-blind study of 65 in patients and 34 out patients suffering from major depressive episodes ( DSM III-R ) . No statistically significant differences between the two treatment groups were noted regarding efficacy ( HDRS , CGI ) or safety ( adverse events , laboratory examination , vital signs ) . Moclobemide ( 300–600 mg daily ) and fluoxetine ( 20–40 mg daily ) would thus appear to be comparable both in antidepressant efficacy and tolerability . Doubling the low dosage in non-responders after 3 weeks result ed in a statistically significant improvement of CGI in the moclobemide group by comparison with the fluoxetine group at study end , suggesting that 600 mg moclobemide/day can still improve the patient 's condition , while 40 mg fluoxetine/day does not . Sexual dysfunction was reported in two patients taking fluoxetine BACKGROUND Sertraline and fluoxetine have pharmacokinetic and pharmacologic differences , which may be of clinical relevance . METHOD A r and omized , double-blind , parallel-group study of 6 weeks ' duration comparing the efficacy and safety of sertraline ( 50 - 100 mg/day ) with those of fluoxetine ( 20 - 40 mg/day ) was conducted in 286 psychiatric out patients with DSM-III-R major depression or bipolar disorder ( depressed ) . Primary efficacy measurements consisted of the 17-item Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impressions ( CGI ) scale . Secondary measurements included the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Raskin Depression Scale , the Covi Anxiety Scale , and the Leeds Sleep Question naire . Additionally , scores for two items and five factors from the HAM-D were analyzed . RESULTS Efficacy was based on 124 evaluable patients in each treatment group . As measured by HAM-D and CGI-Severity scores , there was a significant ( p < .001 ) improvement from baseline to each follow-up visit in both treatment groups with no statistically significant difference between groups . There was also no significant difference in the proportion of responders in each group . CGI-Improvement responder rates were 69 % for sertraline and 67 % for fluoxetine . Results of secondary efficacy measurements followed the same trend , although from the second week of treatment there was a numerical advantage ( not statistically significant ) for sertraline over fluoxetine in improving anxiety symptoms as measured by the total HAM-A score . Headache and nausea were the most frequently reported events for both drugs . The incidence of early patient withdrawals due to treatment-emergent adverse events was 14 % for sertraline and 13 % for fluoxetine . The starting dosage ( sertraline 50 mg/day , fluoxetine 20 mg/day ) was the final dosage in 76 % of patients in both treatment groups . CONCLUSION Sertraline and fluoxetine were equally effective and well tolerated in patients with major depression and associated anxiety The drug difference between a low and a high dosage of haloperidol was investigated in 40 acutely ill schizophrenic patients . All patients were classified as being thought disordered or non-thought disordered schizophrenic using psychometric methods . From the pool of 40 patients two groups were r and omly chosen for the double-blind study , one group receiving 80 mg of liquid haloperidol daily , the other group 16 mg of liquid haloperidol daily . On 5 days during the 21-day treatment the psychopathological state of the patient was evaluated by means of the AMDP system The efficacy of factor-XIII concentrate in the improvement of  postoperative wound healing disorders ( suture dehiscences , fistulae )  was examined in 61 patients . In an open , r and omised , and controlled trial the results ( decrease of wound area , signs of inflammation , wound secretion , drainage volume , contrast x-ray films , and colour photos ) were evaluated twice : open judgement by the clinicians themselves and blind judgement by an independent evaluation committee . The blind evaluation of the clinical data showed relevant general improvement in the patient groups treated with factor-XIII concentrate : 61.9 % ( dosage : 750 IU factor XIII for 3 days ) and 76.2 % ( dosage : 1500 IU factor XIII for 3 days ) as compared to 10.5 % in the control group without factor XIII substitution . The differences were significant ( Mann-Whitney-U-Test , p less than or equal to 0.001 ) . These results would suggest substituting factor XIII activity in plasma above 70 % of normal value in case of wound healing disorders BACKGROUND There has been a paucity of well- design ed studies comparing selective serotonin reuptake inhibitor ( SSRI ) medications in the treatment of depression in the elderly . This multicenter study was design ed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly out patients . A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function . METHOD Two hundred thirty-six out patients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being r and omly assigned to 12 weeks of double-blind , parallel-group treatment with flexible daily doses of either sertraline ( range , 50 - 100 mg ) or fluoxetine ( range , 20 - 40 mg ) . Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings . Secondary outcome assessment s included clinician- and patient-rated measures of depression symptoms and factors , cognitive functioning , and quality of life , as well as plasma drug concentrations , which were correlated with clinical response . RESULTS Both drugs produced a similarly positive response on the primary efficacy measures , with 12-week responder rates of 73 % for sertraline and 71 % for fluoxetine . Sertraline-treated patients showed statistically greater cognitive improvement on several measures . Both drugs were safe and well tolerated . CONCLUSION Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly out patients . Differences in cognitive performance effects deserve further investigation This article presents long-term effects of a r and omized trial evaluating 2 st and ardized , manual-based prevention strategies for families with parental mood disorder :  informational lectures and a brief , clinician-based approach including child assessment and a family meeting .  A sample of 105 families , in which at least 1 parent suffered from a mood disorder and at least 1 nondepressed child was within the 8- to 15-year age range , was recruited . Parents and children were assessed separately at baseline and every 9 to 12 months thereafter on behavioral functioning , psychopathology , and response to intervention . Both interventions produced sustained effects through the 6th assessment point , approximately 4.5 years after enrollment , with relatively small sample loss of families ( < 14 % ) . Clinician-based families had significantly more gains in parental child-related behaviors and attitudes and in child-reported underst and ing of parental disorder . Child and parent family functioning increased for both groups and internalizing symptoms decreased for both groups , with no significant group differences . These findings demonstrate that brief , family-centered preventive interventions for parental depression may contribute to long-term , sustained improvements in family functioning Background Massive duplication of effort occurs when research ers all over the world undertake extensive search es for r and omized controlled trials when preparing systematic review s , when developing evidence -based guidelines and when applying for research funding for eczema treatments . Such duplication wastes valuable re sources . Search ing for r and omized controlled trials of eczema is a laborious task involving scrutiny of thous and s of individual references from diverse electronic data bases in order to obtain a few papers of interest . Clinicians and patients who wish to find out more about a particular treatment are at risk of missing the relevant evidence if they are not trained in electronic bibliographic search ing . Systematic review s can not be relied upon to comprehensively inform current optimal eczema treatments due to incomplete coverage and because many may be out of date .An international , publically available and comprehensive re source which brings together all r and omized controlled trials on eczema treatment using a highly sensitive search has the potential to release more filtered knowledge about patient care to those who need it most and to significantly shorten the duration and costs of many clinical eczema research and guideline projects . DescriptionThe G lobal R e source of E czemA T rials brings together information on all r and omized controlled trials of eczema treatments published from the beginning of 2000 up to the end of 2010 and will be up date d every month . We search ed the Cochrane Central Register of Controlled Trials in The Cochrane Library and the Cochrane Skin Group Specialised Register , MEDLINE , EMBASE , LILACS , AMED and CINHAL data bases . We included 268 RCTs ( 24th March 2011 ) covering over 70 different treatment interventions .The structure of the Global Re source of Eczema Trials allows the user as much , or as little , specificity when retrieving information on trials as they wish , in an easy to use format . For each trial , the data base gives the citation for the published report and also provides enough information to enable a user to decide whether the trial is worth further scrutiny . Conclusions The Global Re source of Eczema Trials has been created to facilitate knowledge mobilization into healthcare and to reduce wastage of research time through unnecessary duplication . The collective time saved by research groups around the world can now be used to make strides in optimising the treatment of eczema , in order to further benefit people with eczema . The data base can be accessed free of charge at http://www.great data INTRODUCTION On average 40 % of all patients suffering from Parkinson s disease ( PD ) undergo bouts of depression . It is thought that this is due to a dysfunction in the orbitofrontal and dorsolateral circuits , together with hypometabolism in the orbital , cau date nucleus and frontal dorsolateral tract regions . AIMS The aim of this study is to compare the effectiveness of low doses of fluoxetin with that of low doses of amitriptyline in controlling depression in patients with PD . PATIENTS AND METHODS The study examined a total of 77 patients ( 34 females and 43 males ) , with an average age of 68.2 years , who had been suffering from PD ( according to the diagnostic criteria of Calne et al , in stage II of Hoehn and Yahr ) for an average of 6.9 years . They were divided r and omly into two groups which received fluoxetin ( 37 patients , dosage : 20 40 mg/day ) or amitriptyline ( 40 patients , dosage : between 25 and 75 mg/day ) . A basal evaluation and four others ( at 3 , 6 , 9 and 12 months of treatment ) were performed , including the STMS ( Short test of mental status ) , the Hamilton scale , and extent of functional disability using the UPDRS . A statistical analysis was performed by comparing the variance of the above mentioned parameters and the c2 test with Yates correction or the Fisher exact two tailed test , to evaluate the reasons for dropping out . In both cases a value of p < 0.05 was accepted as significant . RESULTS 58 patients finished the study . Drop out because of side effects only took place in the group that received amitriptyline ( p < 0.02 ) , which was better than fluoxetin at controlling the depression ( p < 0.009 , 0.001 , 0.002 and 0.00006 ) at 3 , 6 , 9 and 12 months , respectively . CONCLUSIONS At an average dosage of 35.2 mg/day , amitriptyline is effective in controlling the depression presented by patients with PD . However , despite the low dosage , the side effects it caused forced 15 % of the patients ab and on the treatment BACKGROUND Continuation of antidepressant medication ( ADM ) after remission is widely used to prevent depressive relapse/recurrence . Little is known about predictors of ADM use in terms of adherence , dosage , and successful tapering . The current study aim ed to explore beliefs about the causes of depression and recovery ( i.e. , causal beliefs ) and to examine whether they predict ADM use . METHODS The data were drawn from a controlled trial and an extension of this trial with additional experience sampling . In total , 289 remitted patients with recurrent depression ( ADM ≥ 6 months ) were r and omly assigned to Preventive Cognitive Therapy ( PCT ) with ADM tapering , PCT with maintenance ADM , or maintenance ADM alone . Adherence , ADM dosage , and causal beliefs regarding the first and last depressive episodes were explored via question naires . RESULTS Most patients mentioned stressful life events as cause of depression , although more patients tended to endorse external causes for the first episode and internal causes for the last episode . ADM  was most often mentioned as helpful during recovery from both episodes . Over half of all patients were adherent and under half of the patients in the tapering condition were able to complete the taper . Causal beliefs did not predict ADM use . CONCLUSIONS The results suggest that causal beliefs play little role in the use of maintenance ADM . More information is needed on factors contributing to successful tapering . The results must be interpreted with caution as this is not a naturalistic study and the results might be biased toward a more favorable view regarding ADM Major depression disorder is most commonly treated with antidepressants . However , due to their side effects clinicians seek non-pharmacologic options , and one of these is exercise . The literature on the benefits of exercise for depression is extensive . Nevertheless , two recent review s focusing on antidepressants vs. other therapies as a basis for clinical practice guidelines recommended mainly antidepressants , excluding exercise as a viable choice for treatment of depression . The aim of this perspective is to analyze the literature exploring the reasons for this discrepancy . Two categories of publications were examined : r and omized controlled trials ( RCTs ) and meta-analyses or systematic review s. Based on this re assessment , RCTs comparing exercise to antidepressants reported that exercise and antidepressants were equally effective . RCTs comparing exercise combined with antidepressants to antidepressants only reported a significant improvement in depression following exercise as an adjunctive treatment . Almost all the review s examining exercise vs. other treatments of depression , including antidepressants , support the use of exercise in the treatment of depression , at least as an adjunctive therapy . The two review s examining pharmacologic vs. non-pharmacologic therapies as a basis for clinical practice guidelines examined limited evidence on exercise vs. antidepressants . In addition , it is possible that academics and health care practitioners are skeptical of viewing exercise as medicine . Maybe , there is a reluctance to accept that changes in lifestyle as opposed to pharmacological treatment can alter biological mechanisms . Longitudinal studies are needed for assessing the effectiveness of exercise in real clinical setting s , as well as studies exploring dose-response relationship between exercise and depression Many depressed patients do not remit on antidepressant medication despite an adequate dosage and a sufficient duration of treatment.1 This has spawned endeavors to define treatment-resistant depression as a depressive episode that has shown insufficient response to 1 or more adequate trials of an antidepressant.1 What constitutes insufficient , inadequate , or partial response is still a matter of debate . Recently , an operational classification of degree of treatment resistance was proposed,2 with categorical distinctions defined by the percent symptom reduction from baseline as follows : nonresponse , < 25 % reduction ; partial response , 25%–49 % reduction ; and response without remission , ≥ 50 % reduction but without achievement of remission.1 To determine the adequacy and outcome of treatment in a way that can be communicated among clinicians and research ers , it is crucial to employ a reliable and valid instrument . While historical rating of treatment is not as accurate as a prospect i ve trial , there are many instances in which a decision is needed before the next trial is carried out . Several tools have been proposed , such as the  Antidepressant Treatment History Form (ATHF),3 the  Harvard Antidepressant Treatment History (HATH),4 and the Massachusetts General Hospital Antidepressant Treatment Response Question naire (ATRQ).1,5 The ATHF and HATH have the advantage of integrating clinical judgment in the assessment of treatment resistance , but these question naires are quite burdensome.5 The ATRQ ( Appendix 1 ) and accompanying questions are meant to provide clinicians with a user-friendly tool for assessment of prior treatment . It is often the case that a patient remembers whether a past treatment was somewhat helpful , although it is frequently difficult for him or her to remember exactly which antidepressant was taken , how long it was taken , and at what dose . However , it is important that the clinician explore past trials thoroughly using a systematic approach in order to characterize the adequacy of the trial and the degree of improvement . The clinician version of the ATRQ1,5 examines the adequacy of duration and dose of prior and current antidepressant treatments  in a step-by-step procedure . It can not be emphasized enough that , when assessing the duration and dose of clinical trials of antidepressants , clinicians must always inquire about adherence to each treatment trial . In addition , the ATRQ assesses the degree of improvement ( in the most efficacious trial or in all trials during the current episode , depending on the version of the instrument ) on a scale from 0 % ( not improved at all ) to 100 % ( completely improved ) ( Table 1 ) . The previous treatment may have been monotherapy , an augmentation trial , a trial of 2 antidepressants ( combination therapy ) , or a switch to another antidepressant . Our group has adopted conventions to define resistance to each of these approaches . At the outset it is noted that the doses and duration s required for adequate treatment are based on expert consensus1 rather than systematic research . We define an adequate monotherapy trial as a trial lasting at least 6 weeks at a minimum effective dose . In the context of this initial trial , the adequate duration for augmentation or combination treatment is at least 3 weeks . However , a combination trial from the onset ( ie , starting with 2 drugs together ) must be 6 weeks . Six weeks is also required for a switch to a different antidepressant . Each of these trials is considered a new trial . An increase in dose for at least 4 weeks represents optimization and is not considered a new or separate trial . However , if remission is later followed by relapse , a dose increase represents a new trial for the new episode . We recognize that the conventions used to define adequate dose and duration are not established and that other conventions , for example , a duration of 12 weeks , might be preferred . The ATRQ can be adapted to accommo date various definitions of dose and duration . Likewise , the threshold of resistance in terms of percent response may vary , depending on the questions being asked within a given clinical trial Lithium augmentation is one of the best studied strategies for resistant depression . The lithium dosage usually given is around 900 mg/day and plasma level is maintained in the range of 0.5 - 0.8 mEq/L. However , the administration of lithium in this dosage necessitates monitoring of plasma concentration and increases the risk of toxicity and side effects . Since it has been shown that low lithium levels increase serotonin turnover and enhance serotonin neurotransmission , we thought it of interest to assess the efficacy of low dosage lithium augmentation for patients with resistant depression . Fifty one patients suffering from severe unipolar or bipolar depression who had failed to respond to treatment with venlafaxine 300 - 375 mg/day were included in the study and treated as out patients . Patients had previously been exposed to unsuccessful treatment with various antidepressants , mostly SSRIs . After a washout period for previously administered antidepressants of one week , the dosage of venlafaxine was rapidly titrated to 300 or 375 mg/day , corresponding to about 5 mg/kg . The dose remained stable during the next six weeks . Additional antipsychotic medication was allowed to treat psychotic symptoms . Forty seven severely depressed patients who failed to respond to 300 - 375 mg/day venlafaxine  were , in addition , given lithium carbonate in low dosage ( 300 - 450 mg/day ) . The Clinical Global Impression Improvement scale was used as the treatment outcome . A score of 1 or 2 was considered as non-response . All patients gave informed consent to participate in the study . Ratings were performed at baseline and after 1,2 and 5 weeks . Lithium plasma concentration measurements were performed after 1 and 4 weeks . After 5 weeks of augmentation , 51 % of the patients were rated as " much " or " very much " improved . Bipolar patients showed a better response than unipolar ( 64.3 % vs 45.5 % , p<0.038 ) . Most patients ( 76 % ) showed a rapid response ( up tp 7 days ) , and only 2 patients ( 4.6 % ) responded after more than 2 weeks The mean lithium plasma level was 0.33±0.09 mEq/L. No significant differences were found in treatment response with regard to sex , family history , psychotic symptomatology and suicidal ideation . No troublesome side effects were reported . Our results show that treatment augmentation with low lithium dosage may be as effective as augmentation with higher dosage , is well tolerated and does not necessitate monitoring of plasma level . Hence , an initial trial of ugmentation at low dosage lithium may be the preferred first choice in non-emergent situations . The low dosage also minimizes the risk of side effects and drug-drug interactions . Prospect i ve controlled studies to confirm our findings are needed as are larger scale comparisons with therapeutic dose lithium augmentation BACKGROUND This study was design ed to establish the efficacy of the serotonin reuptake blocker fluoxetine in the treatment of posttraumatic stress disorder ( PTSD ) . METHOD 64 subjects ( 22 women and 42 men ; 31 veterans and 33 nonveterans ) with PTSD entered a 5-week r and omized double-blind trial comparing fluoxetine ( N = 33 ) and placebo ( N = 31 ) . RESULTS By Week 5 fluoxetine , but not placebo , significantly reduced overall PTSD symptomatology , as assessed by the Clinician-Administered PTSD Scale ( CAPS ) score . Changes were most marked in the arousal and numbing symptom subcategories .  Non-VA patients responded much better than VA patients . Fluoxetine was an effective antidepressant independent of its effects on PTSD . CONCLUSION Fluoxetine is an effective pharmacotherapeutic agent for treating PTSD and its associated features , particularly in patients without chronic treatment histories Background Early rehabilitation after stroke is essential to help reduce disability . Purpose To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke . Data Sources English- language search es of multiple electronic data bases from April 2009 through July 2018 ; targeted search es to December 2018 for studies of selective serotonin reuptake inhibitors ( SSRIs ) or serotonin-norepinephrine reuptake inhibitors . Study Selection 19 systematic review s and 37 r and omized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke . Data Extraction One investigator abstract ed the data , and quality and GRADE assessment were checked by a second investigator . Data Synthesis Most interventions ( for example , SSRIs , mental practice , mirror therapy ) did not improve motor function . High- quality evidence did not support use of fluoxetine to improve motor function . Moderate- quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living ( ADLs ) . Low- quality evidence supported use of robotic arm training to improve ADLs . Low- quality evidence indicated that antidepressants may reduce depression , whereas the frequency and severity of antidepressant-related adverse effects was unclear . Low- quality evidence suggested that cognitive behavioral therapy and exercise , including mind-body exercise , may reduce symptoms of depression and anxiety . Limitation Studies were of poor quality , interventions and comparators were heterogeneous , and evidence on harms was scarce . Conclusion Cardiorespiratory training , repetitive task training , and transcranial direct current stimulation may improve ADLs in adults with stroke .  Cognitive behavioral therapy , exercise , and SSRIs may reduce symptoms of poststroke depression , but use of SSRIs to prevent depression or improve motor function was not supported . Primary Funding Source U.S. Department of Veterans Affairs , Veterans Health Administration Ketamine , an N-methyl-D-aspartate receptor ( NMDAR ) channel blocker , has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients . However , the marked acute psychological side effects of ketamine complicate the interpretation of both pre clinical and clinical data . Moreover , the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question . Using quantitative electroencephalography ( qEEG ) to objective ly align doses of a low-trapping NMDA channel blocker , AZD6765 ( lanicemine ) , to that of ketamine , we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects . Furthermore , using placebo-controlled data , we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration . Together , these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders A two-phase study was undertaken design ed to investigate the impact of computer-aided drug monitoring on tobramycin concentrations and clinical outcomes in adult patients with cystic fibrosis . In phase one , a baseline ( historical control ) study of drug use patterns was performed . During the second phase , patients admitted for intravenous treatment with tobramycin for acute exacerbations of pseudomonal pulmonary infections were r and omly allocated to one of two schedules . Group A patients had tobramycin dosage regimens decided by clinicians based on pre-existing protocol s using serum tobramycin assay data determined three times weekly . Group B patients had dosage regimens determined by a computerized pharmacokinetic predictive program using both population -based pharmacokinetic parameter estimation and fitting of serum concentration-time data using Bayesian regression . The agreed therapeutic target was a peak serum tobramycin concentration of 8 - 10 mg/L and a trough concentration of 1 - 2 mg/L. There was a major difference between the two groups comparing the number of paired trough and peak concentrations within the target concentration ranges ( group A-14 % ; group B-34.7 % , chi 2 test , P less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Generalized anxiety disorder ( GAD ) is a chronic anxiety disorder , associated with comorbidity and impairment in quality of life , for which improved psychosocial treatments are needed . GAD is also associated with reactivity to and avoidance of internal experiences . The current study examined the efficacy of an acceptance-based behavioral therapy aim ed at increasing acceptance of internal experiences and encouraging action in valued domains for GAD . Clients were r and omly assigned to immediate ( n = 15 ) or delayed ( n = 16 ) treatment .  Acceptance-based behavior therapy led to statistically significant reductions in clinician-rated and self-reported GAD symptoms that were maintained at 3- and 9-month follow-up assessment s ; significant reductions in depressive symptoms were also observed . At posttreatment assessment 78 % of treated participants no longer met criteria for GAD and 77 % achieved high end-state functioning ; these proportions stayed constant or increased over time . As predicted , treatment was associated with decreases in experiential avoidance and increases in mindfulness The Cochrane Collaboration was established in 1993 , following the opening of the UK Cochrane Centre in 1992 , at a time when search ing for studies for inclusion in systematic review s was not well-developed . Review authors largely conducted their own search es or depended on medical librarians , who often possessed limited awareness and experience of systematic review s. Guidance on the conduct and reporting of search es was limited . When work began to identify reports of r and omized controlled trials ( RCTs ) for inclusion in Cochrane Review s in 1992 , there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase . No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major data bases . This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies .Over time , the number of studies indexed as RCTs in the major data bases has grown considerably and the Cochrane Central Register of Controlled Trials ( CENTRAL ) has become the best single source of published controlled trials , with approximately 700,000 records , including records identified by the Collaboration from Embase and MEDLINE . Search filters for various study types , including systematic review s and the Cochrane Highly Sensitive Search Strategies for RCTs , have been developed . There have been considerable advances in the evidence base for method ological aspects of information retrieval . The Cochrane H and book for Systematic Review s of Interventions now provides detailed guidance on the conduct and reporting of search es . Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include : the recently introduced Method ological Expectations for Cochrane Intervention Review s ( MECIR ) programme , which stipulates ' m and atory ’ and ' highly desirable ’ st and ards for various aspects of review conduct and reporting including search ing , the development of St and ard Training Material s for Cochrane Review s and work on peer review of electronic search strategies . Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in search ing for studies for systematic review s. Prospect i ve registration of clinical trials is increasing and search ing trials registers is now m and atory for Cochrane Review s , where relevant . Portals such as the WHO International Clinical Trials Registry Platform ( ICTRP ) are likely to become increasingly attractive , given concerns about the number of trials which may not be registered and /or published . The importance of access to information from regulatory and reimbursement agencies is likely to increase . Cross- data base search ing , gateways or portals and improved access to full-text data bases will impact on how search es are conducted and reported , as will services such as Google Scholar , Scopus and Web of Science . Technologies such as textual analysis , semantic analysis , text mining and data linkage will have a major impact on the search process but efficient and effective updating of review s may remain a challenge . In twenty years ’ time , we envisage that the impact of universal social networking , as well as national and international legislation , will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all . Challenges will remain , however , to ensure the discoverability of relevant information in diverse and often complex sources and the availability of meta data to provide the most efficient access to information . We envisage an ongoing role for information professionals as experts in identifying new re sources , research ing efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic review OBJECTIVE A limited number of r and omized clinical trials show that efficacious pharmacologic treatments exist for comorbid major depressive disorder ( MDD ) and generalized anxiety disorder ( GAD ) . The aims of this effectiveness study were to describe the impact of a depression care management intervention on the persistence of comorbid GAD symptoms in a sample of primary care patients with MDD and to identify risk factors for persistent GAD . METHOD Data were collected from April 2003 to September 2005 for the Telemedicine-Enhanced Antidepressant Management ( TEAM ) study , a multisite , r and omized effectiveness trial targeting US Department of Veterans Affairs ( VA ) primary care patients with depression . Veterans aged 26.59 - 88.36 years received either the  TEAM intervention or usual care in small VA community-based outpatient clinics . The TEAM care management intervention focused on optimizing antidepressant therapy through patient education and activation , symptom monitoring , adherence promotion , and side-effect management .  Veterans who screened positive for MDD using the Patient Health Question naire-9 ( based on DSM-IV criteria ) and who met the Mini-International Neuropsychiatric Interview criteria ( maintaining consistency with DSM-IV-TR ) for comorbid GAD at baseline were selected for the present study ( N = 168 ) . The primary outcome was persistence of GAD at 6 months and 12 months . All predictors available in the TEAM study data that were described in the literature to be associated with influencing GAD outcomes were examined . RESULTS Persistence of depression was the strongest predictor of persistence of comorbid GAD at both 6 months ( OR = 5.75 ; 95 % CI , 2.38 - 13.86 ; P < .05 ) and 12 months ( OR = 15.56 ; 95 % CI , 6.10 - 39.68 ; P < .05 ) . Although the TEAM intervention significantly reduced depression symptom severity , it was not significantly associated with GAD persistence . Insomnia was a significant protective factor for persistence of GAD at 6 months ( OR = 0.66 ; 95 % CI , 0.44 - 0.99 ; P < .05 ) . CONCLUSIONS Early screening for presence of comorbid GAD among those with MDD may be valuable both for further research and for enhancing clinical management of GAD and MDD comorbidity 8 general practitioners and 7 specialists in the field of psychiatry and neurology participated in this study evaluating the results of fluoxetine treatment in out patients with depression in respect to safety and efficacy . They were familiarized with the requisite instruments by video rater training . The study was design ed as a r and omised double-blind parallel study involving 139 patients , comparing the effects of a daily dosage of 20 mg fluoxetine , 40 mg fluoxetine and 50 mg clomipramine . The number of patients treated in each group was 45 , 46 , and 48 , respectively and altogether 125 completed the four-week study ( five visits ) . A comparison of overall efficacy ratings showed significant antidepressant efficacy in all three treatment groups . On day 14 of the study ( visit 4 ) , patients receiving 40 mg fluoxetine showed significantly ( p less than 0.05 ) better global improvement than patients receiving clomipramine .  Treatment was well tolerated by all patients . The frequency of adverse events in response to fluoxetine was lower than under clomipramine treatment . On comparing treatment by psychiatrist and general practitioner no significant differences were found regarding age , sex , number of previous episodes and duration of the recent episode and outcome . Severe depression tended to be treated by psychiatrists ; general practitioners prescribed additional medication less frequently RATIONALE Because some anti-epileptic drugs ( AEDs ) are effective in bipolar affective disorders , the new AED topiramate ( TPM ) may be effective in psychiatric illnesses . TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs . METHODS Charts of 58 consecutive patients , 39 out patients ( 15 males , 24 females ) and 19 in patients ( 6 males , 13 females ) were review ed .  TPM 25 mg . b.i.d . was added to existing therapy and titrated in 50 mg increments every 3 - 7 days . Improvement was rated on a Likert global assessment scale of marked , moderate , mild , or no improvement or worse , based on quality of sleep , appetite , mood , and concentration . RESULTS Of the 58 patients with psychiatric disorders , 44 patients had rapid cycling bipolar disorders characterized by manic , hypomanic , or mixed episodes . Eighteen patients had previously failed to respond to lamotrigine and /or gabapentin in addition to conventional mood stabilizers . Fourteen were Bipolar I , six Bipolar II , and seven mixed , ten patients had cyclothymic disorder , seven had bipolar disorder not otherwise specified . Of the remaining 14 patients , nine had schizoaffective disorder , three patients had dementia and two had psychosis . Mean duration of TPM treatment was 16.0 weeks ; mean TPM dosage approximately 200 mg/day . Thirty-six of 58 ( 62 % ) patients exhibited marked or moderate improvement , usually within days or weeks . Twenty-three of 44 ( 52 % ) patients with bipolar affective disorders showed marked or moderate improvement . Minimal/no improvement was observed in 16 ; six were rated as worse . Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM ( 800 mg ) and tranylcypromine sulfate ( 170 mg ) combined with alcohol . Other adverse effects were minor and included : paresthesias , somnolence , fatigue , impaired concentration and memory , nausea , and diarrhoea . LIMITATIONS This study was performed in a nonr and om open and retrospective fashion . Therefore , any findings are limited by the design of this study . CONCLUSION TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation During treatment with vitamin K antagonists , International Normalized Ratios ( INR ) are determined periodically to maintain a therapeutic level of anticoagulation . We evaluated two existing methods for therapeutic quality control ( linear interpolation and equidivision ) , with regard to their validity and reproducibility . In addition , we proposed and evaluated a ( hybrid ) method that takes into account potential effects of dosage modifications when INRs are far out of the target range . Validity was assessed by deleting intermediary INR results and estimating this INR based on the two surrounding INRs with each of the three methods . The estimated INRs were then compared with the observed INR . Reproducibility of time spent in an INR range was evaluated for each of the three methods by deleting at r and om increasing proportions of INRs and comparing these estimates with the situation without deletions . We found that estimates of time spent in INR categories obtained with equidivision were most reproducible , but least valid . The hybrid method showed slightly higher validity and reproducibility in comparison with linear interpolation . Since these differences were small , linear interpolation is preferable to the hybrid method , since the calculations involved are easier Summary . The success in achieving therapeutic international normalized ratio ( INR ) targets in the control of warfarin using a whole‐blood point‐of‐care testing ( POCT ) monitor ( CoaguChek ) in a community clinic was compared with hospital laboratory coagulometer prothrombin time ( PT ) testing in a r and omized crossover study . Forty‐six patients were r and omized into two groups . At each visit , capillary blood was taken for the POCT monitor and venous blood for the laboratory coagulometer . In Group 1 , for 6 months , dosage was based on the CoaguChek and for the second 6 months on the coagulometer . In the second group , the order was reversed . Dosages were determined using the dawn ac computer programme . Success was assessed by the percentage of time patients were maintained within the INR targets . Agreement between laboratory and monitor INR , and patient satisfaction were also assessed . Results with the POCT monitor compared well with the hospital coagulometer . Time in INR target range between the groups was similar , with 60·9 % on the POCT monitor and 59·3 % with the laboratory coagulometer in Group 1 and in Group 2 , respectively , 64·3 % and 63·4 % with no significant difference in mean INR . An INR above 4·0 gave some discrepant results . International Sensitivity Index calibrations of the two test systems indicated that the INRs were dependable . Patient question naires showed greater satisfaction with community POCT monitoring The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder ( PD ) . Twenty-five out patients having PD with or without agoraphobia were included . These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day . Treatment-resistant PD was defined as a less than 20 % reduction in score on the Panic Self- Question naire ( number of attacks per week ) ( PSQ ) and the Clinical Anxiety Scale With Panic Attacks ( CAS+PA ) . These patients continued to receive fluoxetine 20 mg/day and were r and omly assigned to additionally receive either pindolol ( 2.5 mg three times daily ) or placebo for the following 4 weeks . Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety , the Hamilton Rating Scale for Depression ( HAM-D ) , the CAS+PA , the NIMH Anxiety Scale , the PSQ , and the Clinical Global Impression Scale . The data were analyzed using a repeated- measures analysis of variance ( ANOVA ) and a t-test for independent sample s. Patients treated with the combination of pindolol and fluoxetine ( N = 13 ) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales , with the exception of HAM-D. The statistical differences were shown using the repeated- measures ANOVA ( baseline , week 2 , week 4 ) and also with t-tests from the second week of the trial . These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD OBJECTIVE Loss of response to a previously effective antidepressant is a common clinical problem . Retrospective analyses have shown that the pattern of response during antidepressant treatment ( late onset and persistent versus other patterns ) can be used to predict relapse during continuation and maintenance treatment and possibly to identify placebo responses to treatment . This study was design ed to test the predictive value of response pattern prospect ively and to examine the data for other predictors of relapse . METHOD Five hundred seventy persons with major depressive disorder were treated with fluoxetine for 12 weeks and their pattern of response was determined . Those who responded ( N=292 ) underwent r and om assignment , under double-blind conditions , to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse . Survival analysis was used to examine the effect of covariates on relapse . RESULTS Although fluoxetine was significantly more effective than placebo during maintenance treatment , this chronically ill group had a high rate of relapse . Contrary to previous findings , a pattern of acute response was not predictive of relapse . Chronicity , symptom severity , a neurovegetative symptom pattern , and female gender were all associated with a significantly greater risk of relapse , with no difference observed between fluoxetine and placebo . CONCLUSIONS The pattern of response to acute treatment appears to be inconsistently predictive of relapse . There is a high rate of relapse with both active medication and placebo in patients with chronic depression . Illness characteristics predict loss of response both to fluoxetine and to placebo . No variable examined was predictive of differential relapse rates between fluoxetine and placebo The temporal dimension , particularly anticipation , appears to he a very important component in the underst and ing of depressed patients . In a 90-day multieentre study , the efficacy and acceptability of amineptine and fluoxetine were compared in 169 patients with major depression . Comparison of the two antidepressants was bused on double-blind methods , after r and om allocation of the treatments between two parallel groups . The two drugs did not differ over the whole course of the study , but the improvement in scores on day 4 was globally more marked in the amineptine than the fluoxetine group . Intragroup analysis showed that amineptine was significantly superior to fluoxctine on the retardation pole of the mood , anxiety , retardation , danger scale . The positive effect of amineptine on anticipation may enable the depressed patient to make plans for the future . Anticipation may be a key dimension to be more precisely explored in specific psychopharmacological protocol s with antidepressants Abstract Objectives . This 2013 up date of the practice guidelines for the biological treatment of unipolar depressive disorders was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry ( WFSBP ) . The goal has been to systematic ally review all available evidence pertaining to the treatment of unipolar depressive disorders , and to produce a series of practice recommendations that are clinical ly and scientifically meaningful based on the available evidence . The guidelines are intended for use by all physicians seeing and treating patients with these conditions . Methods . The 2013 up date was conducted by a systematic up date literature search and appraisal . All recommendations were approved by the Guidelines Task Force . Results . This first part of the guidelines ( Part 1 ) covers disease definition , classification , epidemiology , and course of unipolar depressive disorders , as well as the management of the acute and continuation phase treatment . It is primarily concerned with the biological treatment ( including antidepressants , other psychopharmacological medications , electroconvulsive therapy , light therapy , adjunctive and novel therapeutic strategies ) of adults . Conclusions . To date , there is a variety of evidence -based antidepressant treatment options available . Nevertheless there is still a substantial proportion of patients not achieving full remission . In addition , somatic and psychiatric comorbidities and other special circumstances need to be more thoroughly investigated . Therefore , further high- quality informative r and omized controlled trials are urgently needed The effects of trimipramine , a tricyclic antidepressant ( TCA ) with atypical pharmacological properties , and fluoxetine , a selective serotonine reuptake inhibitor ( SSRI ) , were compared in an exploratory analysis using mood and polysomnographic parameters during a six-week double-blind trial in 19 depressed geriatric patients . In sleep EEG measures , trimipramine demonstrated clear-cut effects on sleep measures result ing in higher values for sleep efficiency , total sleep time , stage 2 sleep , and shorter wake time . Under fluoxetine treatment , the proportion of REM sleep was decreased and REM latency was lengthened , whereas no change in REM sleep parameters was observed in the trimipramine group . The present data suggest that early antidepressant effects of medication occur independently of drug-induced changes in objective measures of sleep , i.e. suppression of REM sleep OBJECTIVES Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders . We addressed these issues by examining data from a prospect i ve longitudinal community study to ( i ) determine the cumulative incidence of mood episodes and disorders in the first three decades of life ; ( ii ) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa ; and ( iii ) determine the clinical and treatment characteristics of these subjects . METHODS Using the Munich-Composite International Diagnostic Interview , clinical ly trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects ( aged 14 - 24 at baseline and 21 - 34 at third follow-up ) . RESULTS The estimated cumulative incidence at age 33 was 2.9 % for manic , 4.0 % for hypomanic , 29.4 % for major depressive , and 19.0 % for minor depressive episodes ; overall , 26.0 % had unipolar major depression , 4.0 % bipolar depression , 1.5 % unipolar mania , and 3.6 % unipolar hypomania ( no major depression ) . Overall , 0.6 % and 1.8 % had unipolar mania or hypomania , respectively , without indication for even minor depression . A total of 3.6 % of the initial unipolar major depression cases subsequently developed (hypo)mania , with particularly high rates in adolescent onset depression ( < 17 years : 9 % ) . A total of 49.6 % of the initial unipolar mania cases subsequently developed major depression and 75.6 % major or minor depression . While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases , bipolar cases did not significantly differ in mania characteristics from unipolar mania cases . CONCLUSIONS Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood , a time period when both the recognition and the intervention rates by the healthcare system are rather low . ' Conversion ' to bipolar disorder is limited in initial unipolar depression , but common in initial unipolar mania . The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings OBJECTIVES Depression in older patients contributes to personal suffering and family disruption and increases disability , medical morbidity , mortality , suicide risk , and healthcare utilization . The majority of clinical trials of antidepressant treatments are conducted in younger patients . For this reason , clinicians often have to extrapolate from studies in population s that do not present the same problems as older patients . For example , older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment . Older patients as a rule need to be on many medications , some of which may contribute to depression and /or interact with antidepressants . Finally , older adults metabolize medications slowly and are more sensitive to side effects than younger patients . Because of these complexities , we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature . METHOD After review ing the literature and convening a work group of experts , we prepared a written survey with 64 questions that asked about 857 options . 618 of the options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or to check a box to indicate their preferred answer . We sent the survey to 50 national experts on geriatric depression , all of whom completed it . Consensus on each option was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 89 % of the options rated on the 9-point scale . The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment . For unipolar nonpsychotic major depression , the preferred strategy is an antidepressant ( selective serotonin reuptake inhibitor [ SSRI ] or venlafaxine XR preferred ) plus psychotherapy . For unipolar psychotic major depression , the treatment of choice is an antidepressant ( SSRI or venlafaxine XR ) plus one of the newer atypical antipsychotics . Electroconvulsive therapy is also first line . For dysthymic disorder or persistent milder depression , the experts recommend combining an antidepressant ( SSRIs preferred ) and psychotherapy . If the patient has a comorbid medical condition ( e.g. , hypothyroidism ) that is contributing to the depression , the experts recommend treating both the depression and the medical condition from the outset . The SSRIs were the top-rated antidepressants for all types of depression . Among them , the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline . Paroxetine was another first-line option , and fluoxetine was rated high second line . The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy , supportive psychotherapy , problem-solving psychotherapy , and interpersonal psychotherapy . The experts also give strong support to including appropriate psychosocial interventions ( e.g. , psychoeducation , family counseling , visiting nurse services ) in the treatment program . The majority of experts would continue treatment with antidepressant medication for at least 1 year if a patient has had a single episode of severe unipolar major depression , for 1 - 3 years for a patient who has had 2 such episodes , and for longer than 3 years if there is a history of 3 or more episodes . CONCLUSIONS The experts reached a high level of consensus on the appropriateness of including both antidepressant medication , specifically SSRIs , and nonpharmacological modalities in treatment plans for severe depression . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide direction for addressing common clinical dilemmas in older individuals . They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions . Nonetheless , the guidelines can not address the complexities involved in the care of each individual patient and can be most helpful in the h and s of experienced clinicians Of a total of 581 consecutive depressed subjects attending psychiatric services of 6 centres in Finl and , 183 patients were eligible and completed a 6-week r and omised double-blind trial with either moclobemide or fluoxetine . Of these , 32 ( 17.5 % ) patients met the DSM-III-R criteria for mood disorder with a seasonal ( winter ) pattern and 19 patients ( 10.5 % ) met the original criteria for seasonal affective disorder ( SAD ) . There were no significant difference in the antidepressive response to the treatment between the patients with SAD and other depressive disorder . The treatment of 6 weeks with either moclobemide ( 300 - 450 mg daily ) or fluoxetine ( 20 - 40 mg daily ) result ed in a full remission in 15 ( 52 % ) patients with SAD and in 44 ( 37 % ) patients with other depressive disorder . Altogether , 23 ( 79 % ) and 83 ( 70 % ) patients , respectively , got significant benefit from the treatment . The improvement in the health-related quality of life in terms of ability to work was significantly more extensive in the patients with SAD assigned to receive moclobemide compared with the other depressive patients allocated to the same medication . Subjects who in addition met the operational criteria for atypical depression were equally distributed into the SAD and other depressive patient groups OBJECTIVE Because many women who receive pharmacologic therapy with antidepressants are also prescribed oral contraceptives , it is important to assess the risk of clinical ly significant drug interactions . We review ed the United States fluoxetine clinical trial data base , specifically analyzing women ages 18 to 45 years , for differences in safety , antidepressant efficacy , and unplanned pregnancies that were associated with oral contraceptive use . STUDY DESIGN Data from 17 double-blind , placebo-controlled clinical trials in 1698 women were analyzed retrospectively . A subgroup of women with oral contraceptive use was compared with a subgroup of women with no  oral contraceptive use . Differences in treatment-emergent adverse events , unplanned pregnancies , and 17-item Hamilton Depression Scale ( HAMD-17 ) scores were analyzed . RESULTS The only treatment-emergent adverse events that showed a statistically significantly different odds ratio for oral contraceptive use versus no oral contraceptive use were headache , asthenia , and pain . There was not a statistically significant interaction in the incidence of unintended pregnancies ( P = .111 ) or in the changes from baseline in HAMDD-17 scores . CONCLUSION There is no clinical evidence that concomitant use of oral contraceptives and fluoxetine affects the safety or efficacy of either agent
Conclusions : International differences in prescriber behaviour may influence , and in turn be influenced by , the conduct of clinical trials .
Objective : International differences are thought to exist in dosages used by clinicians treating mood disorders .
This study examined international dosage differences in antidepressant clinical trials , using a data base formed and maintained as a component of a Cochrane review of comparative clinical trials of fluoxetine .