A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression. A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache. Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression. Amitriptyline, clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical remission in a double-blind, randomized trial of amitriptyline and paroxetine. Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison. Costs and outcomes of use of amitriptyline, citalopram and fluoxetine in major depression: exploratory study. Clinical research on the therapeutic effect of the electro-acupuncture treatment in patients with depression. Clovoxamine in the treatment of depressed outpatients: a double-blind, parallel-group comparison against amitriptyline and placebo. Fluoxetine in Major Depression: Efficacy, Safety and Effects on Sleep Polygraphic Variables LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial. Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression. Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials. Alprazolam and amitriptyline in the treatment of major depressive disorder: a double-blind clinical and sleep EEG study. Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial Comparative effects of amitriptyline and amineptine in patients affected by anxious depression. A double blind, placebo-controlled pilot study of galantamine augmentation of antidepressant treatment in older adults with major depression. Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study. A collaborative study of a new antidepressant, viloxazine, in neurotic and endogenous depressives. Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients Antidepressant response and plasma concentrations of bupropion. Platelet alpha-2 adrenoreceptor activity pre-treatment and post-treatment in major depressive disorder with melancholia. Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study. Antidepressants and inflammatory bowel disease: a systematic review The analgesic effect of amitriptyline on chronic facial pain The therapeutic efficacy of paroxetine: (a) an open study in patients with major depression not responding to antidepressants; (b) a double‐blind comDarison with amitriptyline in I depressed outpatients Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression. Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial. Maintenance therapy of depression. [Comparative study of age-related effectiveness of tri- and tetracyclic antidepressants]. Is the Comparison between Exercise and Pharmacologic Treatment of Depression in the Clinical Practice Guideline of the American College of Physicians Evidence-Based? Resistin and adiponectin in major depression: the association with free cortisol and effects of antidepressant treatment. Paroxetine versus amitriptyline in patients with recurrent major depression: A double-blind trial A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial. Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline. Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. A Double‐Blind Comparison of Paroxetine, Imipramine and Placebo in Depressed Outpatients The treatment of depression in patients with epilepsy. A double-blind trial. Combination tricyclic antidepressant and lithium maintenance medication in unipolar and bipolar depressed patients. Monoamine oxidase inhibitors revisited: what you should know. Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome Fluoxetine, but not Tricyclic Antidepressants, Potentiates the 5-Hydroxytryptophan-Mediated Increase in Plasma Cortisol and Prolactin Secretion in Subjects with Major Depression or with Obsessive Compulsive Disorder Treatment of depression in patients with breast cancer: a comparison between paroxetine and amitriptyline Continuation therapy with amitriptyline in depression. Experimental Examination of Trazodone Amitriptyline in the Treatment of Anorexia Nervosa: A Double‐Blind, Placebo‐Controlled Study Desipramine relieves postherpetic neuralgia. A controlled trial of maprotiline (Ludiomil) in depressed outpatients. Efficacy and Tolerability of Reboxetine Compared with Citalopram: A Double-blind Study in Patients with Major Depressive Disorder A comparative study of milnacipran and imipramine in the treatment of major depressive disorder A double-blind, randomized, fixed-dose trial of fluoxetine vs. amitriptyline in the treatment of major depression complicating Alzheimer's disease. Trazodone in depressed outpatients. Paroxetine versus amitriptyline for treatment of depression associated with rheumatoid arthritis: a randomized, double blind, parallel group study. Prevention of relapse in residual depression by cognitive therapy: a controlled trial. Differential effect of amitriptyline and bupropion on primary and secondary depression: a pilot study. Controlled comparison of two doses of milnacipran (F 2207) and amitriptyline in major depressive inpatients Controlled trial of zimelidine, a 5-HT reuptake inhibitor, for treatment of depression. Effect of tricyclic antidepressants on individual symptoms. A double‐blind study to compare the effectiveness and tolerability of paroxetine and amitriptyline in depressed patients A randomized, within‐patient, cross‐over, placebo‐controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain
BACKGROUND This study was design ed to compare the efficacy , safety , tolerability profiles , and effects on quality of life of the serotonin selective reuptake inhibitor antidepressant sertraline versus the nonselective tricyclic antidepressant amitriptyline and placebo in patients with major depression . METHOD Out patients with DSM-III-R major depression were r and omly assigned to double-blind treatment for 8 weeks with sertraline ( 50 - 200 mg daily ) , amitriptyline ( 50 - 150 mg daily ) , or matching placebo . Assessment s included the Hamilton Rating Scale for Depression , Montgomery-Asberg Depression Rating Scale , Clinical Global Impressions-Severity of Illness scale , Clinical Global Impressions-Improvement scale , Global Assessment Scale , Profile of Mood States , Beck Depression Inventory , Quality of Life Enjoyment and Satisfaction Question naire , and Health-Related Quality of Life battery . RESULTS All treatment groups demonstrated statistically significant improvement from baseline in depression ratings by Week 1 and thereafter . The antidepressant effects of amitriptyline and sertraline were significantly ( p < .05 ) greater than placebo and did not differ significantly from each other . Sertraline was associated with significantly ( p < .05 ) greater subjective ( i.e. , patient-rated ) improvement in mood than amitriptyline or placebo . Both active drugs were associated with greater improvements than placebo on most quality of life measurements . On several items , sertraline , but not amitriptyline , was superior to placebo . There was a discernible effect of sertraline earlier than amitriptyline on most quality of life scales .  Amitriptyline therapy was associated with significantly more treatment-related adverse events , and discontinuations due to treatment-related adverse events , in comparison to both sertraline and placebo therapy . CONCLUSION Sertraline and amitriptyline each were effective treatments for major depression as assessed by both physician- and patient-rated scales . These results show that sertraline therapy is better tolerated than amitriptyline therapy . Quality of life was also improved by effective antidepressant treatment , with sertraline showing a tendency to produce greater improvements on quality of life measures OBJECTIVE To assess the response to a serotonergic/noradrenergic tricyclic antidepressant , amitriptyline ( AMI ) , in a group of adolescents with treatment-resistant major depressive disorder ( MDD ) . METHOD Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week r and omized , controlled trial with a flexible dose of AMI or placebo . RESULTS There were no differences between patients taking AMI ( n = 13 ) and placebo ( n = 14 ) . Both treatment groups showed approximately 70 % to 80 % improvement on the clinical outcome measurements , and 65 % to 70 % showed functional improvement . At the end of the protocol , 30 % of patients still fulfilled criteria for MDD and had impaired functioning . Patients taking AMI experienced significantly more dry mouth and tachycardia . The final AMI dose was 173.1 mg/day + /- 56.3 mg/day ; blood levels were 226.2 ng/mL + /- 80.8 ng/mL. CONCLUSIONS No significant differences were found between AMI and placebo , in part because of the high placebo response rate . Although both treatment groups showed substantial response , at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression . This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD 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 Five hundred four out patients suffering from a major depressive episode were r and omly assigned to receive either amitriptyline , doxepin , alprazolam , or placebo . The study was conducted in three treatment centers during a six-week period . All three active medications produced significantly more clinical improvement than did placebo , irrespective of the patient 's initial anxiety , depression , and psychomotor retardation and irrespective of the patient 's assignment to various subtypes of depression , including the DSM-III melancholia subtype . Compared with placebo , sedation was reported more frequently with all three medications , whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants , but not for alprazolam Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline ( median dose 125 mg ) . The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice .  Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment . The effects of the antidepressant were on the core symptoms of depression , and were apparent in all but the most mildly ill patients . The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice OBJECTIVES : Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache , only few studies have investigated the efficacy of this treatment and the results are contradictory . In addition , the new selective serotonin reuptake inhibiting antidepressants , which are widely used in depression and of potential value in pain management , have never been investigated in a placebo controlled study of tension-type headache . The aim was to evaluate the efficacy of amitriptyline and of the selective serotonin reuptake inhibitor citalopram in chronic tension-type headache . METHODS : Forty non-depressed patients with chronic tension type headache were included in a 32 week , double blind , placebo controlled , three-way crossover study . RESULTS : Thirty four patients completed the trial .  Amitriptyline reduced area under the headache curve by 30 % compared with placebo ( P = 0.002 ) , whereas citalopram had no significant effect ( P = 0.68 ) . Explanatory analyses showed that amitriptyline significantly reduced the duration of headache ( P = 0.01 ) , headache frequency ( P = 0.01 ) , and intake of analgesics ( P = 0.02 ) but not headache intensity ( P = 0.12 ) . CONCLUSION : Although amitriptyline did not eliminate the headache , it provided a clinical ly important reduction of headache in the majority of otherwise treatment resistant patients . The differential effect of amitriptyline and citalopram indicates that mechanisms other than inhibition of serotonin reuptake are involved in the analgesic effect of the tricyclic antidepressants . Amitriptyline , but not citalopram , is valuable in the prophylactic treatment of chronic tension type headache Depressions in general practice tend to be mild and non-endogenous . The value of antidepressants and indications for their use in such depressions are not well documented . One hundred and forty one general practice depressives were treated from four to six weeks with amitriptyline in median dose 125 mgs daily or placebo in a r and omised controlled trial . Significant drug placebo differences were apparent by two weeks and were strong by six weeks . Detailed examination of symptom ratings showed that the effect was a true antidepressant one , on core symptoms of depression . Interactions were examined between drug-placebo differences and a range of predictor characteristics . There were no significant interactions for demographic characteristics , history of illness or endogenous depression in terms of symptom pattern , absence of life stress or non-neurotic personality . Drug was superior to placebo in all subgroups . Only for initial severity of illness were significant interactions found . Amitriptyline was superior to placebo in probable and definite major depressions on the Research Diagnostic Criteria but not in minor depressions . It was also superior to placebo in patients with initial Hamilton Scale scores of more than 12 , but not 6 - 12 . Overall these findings indicate that tricyclic antidepressant is of clear therapeutic benefit in a spectrum of milder depressions except for the most mild of these OBJECTIVE To determine amitriptyline 's ( AMI )  efficacy in the acute treatment of adolescent major depressive disorder ( MDD ) . METHOD Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD , diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children ( K-SADS ) , participated in a 2-week placebo-washout followed by an 8-week , r and omized , double-blind , parallel- design , placebo-controlled trial of AMI , 5 mg/kg per day . The K-SADS nine-item scale , the Hamilton Depression Rating Scale , and the Clinical Global Impressions rating scale were used as outcome measures . RESULTS Thirty-one subjects were r and omized ( 18 AMI , 13 placebo ) . Twenty-two subjects were study completers ( 12 AMI , 10 placebo ) . AMI 's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data . Perhaps the primary limitation of the current study is its small sample size . CONCLUSION No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD No longer prescribed only for vegetative signs of depression , tricyclic antidepressants also lessen depressive cognitive distortions . Less clear is whether they ameliorate depressed patients ' other cognitive deficits in memory , information processing speed , and psychomotor performance . We tested the alternative hypothesis that amitriptyline , because of its anticholinergic and sedative properties , would exacerbate depressed patients '  cognitive disturbances .  Depressed out patients received double-blind  placebo ( n=15 ) , amitriptyline  ( n=10 ) , or clovoxamine fumarate  ( n=10 ) , a serotonin reuptake inhibitor relatively lacking in anticholinergic properties . Depression , memory , and psychomotor performance were assessed at baseline and after 7 and 28 days of drug treatment . Depression was alleviated after all treatments , including placebo . Only amitriptyline impaired performance on tests of memory , producing a significant decrement , relative to placebo , after 4 weeks of treatment . None of the treatments adversely affected performance on psychomotor tasks . These findings add to the evidence that antidepressant drugs with high anticholinergic activity can impair memory , despite alleviation of depression OBJECTIVE There is substantial evidence that depression constitutes a risk factor for type 2 diabetes mellitus . A recent study has shown that high salivary cortisol levels are associated with decreased insulin sensitivity in unmedicated , depressed patients . Further , antidepressive treatment might have differential effects on hypothalamus-pituitary-adrenal ( HPA ) system activity . Therefore , the aim of the present study was to examine whether insulin sensitivity improves during anti-depressive treatment in depressed patients with declining HPA system activity . METHOD Eighty in patients with an episode of major depressive disorder ( DSM-IV criteria ) were treated in a double-blind , r and omized protocol with either amitriptyline or paroxetine over a period of 5 weeks . After 6 drug-free days , an oral glucose tolerance test was performed on day 1 and again 35 days after antidepressive treatment . For quantification of free cortisol levels , saliva was obtained daily at 8:00 a.m. during weeks -1 ( washout ) and 5 . The study was conducted from May 2005 to December 2005 . RESULTS The insulin sensitivity index(Matsuda ) increased in only those patients who remitted from major depressive disorder as a result of treatment with either antidepressant ( F = 7.0 , df = 1,74 ; p < .01 ) , while correcting for body mass index . Further , cortisol concentrations declined in remitters and responders to amitriptyline ( F = 2.1 , df = 1,70 ; p < .05 ) , but not in any other subgroup . CONCLUSION Successful antidepressive treatment with either a selective serotonin reuptake inhibitor or a tricyclic substance increases the sensitivity to insulin in nondiabetic depressed patients . The herein presented longitudinal data do not exclude the HPA system as a major contributor to insulin resistance in depressed patients , but underscore the assumption of additional factors Although common in clinical setting s , major depressive disorder with associated anxious symptoms ( ' anxious depression ' ) has not been well studied in antidepressant clinical trials . The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients . After a single-blind placebo run-in period of 2 weeks , patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks . Assessment instruments included : 21-item Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , Clinical Global Impressions , Raskin Depression Scale and Covi Anxiety Scale . A total of 157 patients were r and omized to either fluoxetine or amitriptyline . Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50 - 250 mg/day ( mean of 138.1 mg/day ) . Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor . Unwanted effects were more frequent and more severe in the amitriptyline-treated patients . Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety .  Since fluoxetine was far better tolerated , it is a promising alternative for this frequent and disabling condition BACKGROUND The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants . The aim of the study was to compare the costs and outcomes of using amitriptyline , citalopram and fluoxetine in the treatment of major depression . METHODS Ninety patients ( 69 women ) with a mean age of 44.5 years ( S.D. = 14.3 ) suffering from major depression were treated with amitriptyline ( N = 31 ) , citalopram ( N = 29 ) and fluoxetine ( N = 30 ) . Direct medical costs and effectiveness ( indicated by the number of hospitalization-free days ) were assessed in a prospect i ve , open , intent-to-treat study . RESULTS Neither cost nor effectiveness were significantly different among the treatment groups . CONCLUSION Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies . There is no advantage in restricting patients from treatment with SSRIs , which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants Electroacupuncture ( EA ) stimulation has been found to influence the brain ( norepinephrine metabolism in experimental animals ) . Preliminary clinical research has shown that EA treatment is as effective as amitriptyline for patients with depression . In this study , two consecutive clinical studies on the treatment of depression with EA are conducted . The first study was double blind placebo controlled , in which 29 depressed in patients were recruited . Patients were r and omly divided into three groups : EA + placebo ; amitriptyline ; and EA + amitriptyline . They received EA and /or amitriptyline treatment for 6 weeks . The Hamilton Rating Scale for Depression , Clinical Global Impression and ASBERG scales for the side effect of antidepressants were used to evaluate the therapeutic efficacy and side effects . Based on the results and research protocol of the first study , a multi-centered collaborative study was conducted , in which 241 in patients with depression were recruited . Patients were r and omly divided into two treatment groups : the EA + placebo and the amitriptyline groups . The results from both studies showed that the therapeutic efficacy of EA was equal to that of amitriptyline for depressive disorders ( P > 0.05 ) . Electro-acupuncture had a better therapeutic effect for anxiety somatization and cognitive process disturbance of depressed patients than amitriptyline ( P < 0.05 ) . Moreover , the side effects of EA were much less than that of amitriptyline ( P < 0.001 ) . The article suggested that EA treatment was an effective therapeutic method for depressive disorders . Particularly , it was a treatment of choice for depressed patients who were unable to comply with the classic tricyclic antidepressants because of their anticholinergic side effects . The possible mechanism of EA treatment is discussed In a double-blind , r and om-assignment , parallel-group trial , out patients with major depression received either the new antidepressant clovoxamine , the tricyclic amitriptyline , or placebo for 6 weeks . By an " improvement " criterion of 50 % or greater improvement in the Hamilton Depression Scale ( HAM-D ) total score , 88 % of clovoxamine completers improved versus 75 % with amitriptyline and 43 % with placebo ; however , due to small numbers , the differences failed to reach statistical significance . Diminished salivary flow was significantly greater with amitriptyline , as were complaints of dry mouth , somnolence , dizziness , and headache . Nausea and vomiting were more common in the clovoxamine-treated group . With amitriptyline , but not with clovoxamine , memory performance declined over a month . However , psychomotor performance was not affected Fluoxetine ( 60 mg ) , a selective inhibitor of the reuptake of 5-HT , was compared in a double-blind trial to amitriptyline ( 150 mg ) in a sample of 34 patients fitting the Research Diagnostic Criteria for a major depressive disorder . Patients were studied after a drug washout period of 10 days and an active treatment period of 42 days . Sleep polygraphic recordings were performed before and at the end of the study . As indicated by the significant decrease in the Hamilton Depression scale and the Montgomery Asberg Depression scale , fluoxetine showed similar antidepressant effects to amitriptyline with significantly fewer adverse effects . Fluoxetine and amitriptyline decreased the amount of REM sleep , a well known effect of classical antidepressants . Fluoxetine showed some specific effects on sleep continuity ( potentially dose related ) as indicated by the significant increase in the number of awakenings and in stage shifts , without interfering with the therapeutic response Up to now , the antidepressant efficacy of the extract of St. John 's wort , LI 160 , has been compared to imipramine and maprotiline , demonstrating similar antidepressant efficacy in mildly to moderately depressed patients , treated either with LI 160 or the respective synthetic comparator . In the study reported here , LI 160 ( total daily dose : 900 mg ) was compared with the sedating tricyclic amitriptyline ( total daily dose : 75 mg ) in a controlled , r and omized , multicentre trial . At the end of the 6-week study , the major target variable , the Hamilton Depression Scale response rate , exhibited no statistically significant difference between the groups , although a tendency for a better response rate was seen in the amitriptyline group . The secondary efficacy parameters , decreases in the total Hamilton Depression and Montgomery-Asberg scores , showed a significant advantage for amitriptyline , but only at week 6 . With regard to tolerability , LI 160 was clearly superior to amitriptyline , particularly in relation to anticholinergic and Central Nervous System adverse events . Thus , 37 % of the LI 160 treated patients reported adverse events , compared to 64 % in the amitriptyline group . This considerable superiority in tolerability for LI 160 in relation to amitriptyline , could confer an advantage in improving compliance for antidepressant pharmacotherapy General practice depressives were treated for 6 weeks with amitriptyline or placebo in a controlled trial . Overall , drug was found strongly superior to placebo . Interactions were examined between drug effects and a number of variables , principally reflecting demographic characteristics , history of illness , severity of illness , and endogenous depression separately in symptoms and stress . Only in the area of severity were significant interactions found . Amitriptyline was superior to placebo in probable or definite major depression on the Research Diagnostic Criteria , but not in minor depression . It was also superior to placebo in subjects with initial scores on the Hamilton Depression Scale of 13 - 15 , and 16 or more , but not with lower scores . Findings indicate that tricyclic antidepressants are of considerable benefit in relatively mild depressions , except in the mildest range The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinical ly for the schizophrenic patient who becomes depressed . However , the value of the combination for these patients has not been clearly demonstrated . This report presents results of a double-blind , r and omized , placebo-controlled clinical trial design ed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed . Results showed that the addition of amitriptyline to perphenazine , when compared with perphenazine alone , was more effective in reducing symptoms of depression after four months of treatment , but less effective in reducing thought disorder . The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be review ed The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants ( TCAs ) , and the frequency and type of adverse events , have made the treatment of depression in this group difficult . The selective serotonin reuptake inhibitors ( SSRIs ) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs . We compared the therapeutic actions and side effects produced by citalopram , the most selective SSRI available , with amitriptyline in a group of elderly patients ( aged 65 and older ) diagnosed with major depression . In a double-blind , double-dummy , parallel-group , multicenter comparison of citalopram ( 20 or 40 mg/day ) and amitriptyline ( 50 or 100 mg/day ) , patients who did not respond to placebo during a 1-week single-blind phase were r and omly assigned to receive citalopram or amitriptyline for 8 weeks . Efficacy measures included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Depression Scale ( HAMD ) , and Clinical Global Impressions . Both drug treatments produced equivalent time-related declines in severity of depression , so that by 8 weeks slightly more than 50 % of the patients in each group experienced marked recovery , defined as MADRS scores < or = 12 . Amitriptyline produced a greater overall incidence of adverse events , including a significantly higher ( P < 0.001 ) percentage of patients reporting dry mouth ( 34 % vs. 7 % ) , as well as a significantly higher ( P < 0.02 ) incidence of somnolence . Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group . For only one event ( nausea ) did the citalopram group report a significantly greater ( P = 0.012 ) incidence ( 12.8 % vs. 4.8 % ) . On the basis of these results , it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly . Because of its low incidence and low magnitude of side effects , citalopram seems especially useful in private practice A double-blind , placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline , a specific serotonin uptake inhibitor . Patients with DSM-III-defined major depression r and omly received either sertraline  ( N = 149 ) , amitriptyline ( N = 149 ) , or placebo ( N = 150 ) once daily for the 8-week study period . The mean final daily medication dose for the all- patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups , respectively . As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale , both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline ( p less than or equal to .001 ) than the placebo group . The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group . The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo We performed a r and omized , double-blind clinical trial comparing the efficacy and safety of zimelidine with amitriptyline and placebo in out patients with major depression , in particular patients with mixed anxiety/depressive symptomatology . Overall , amitriptyline was more effective than zimelidine and placebo after 4 weeks of treatment . However , when those patients with more severe depression were specifically examined , both antidepressants were equal in efficacy and superior to placebo . We also found no evidence for a greater likelihood of a zimelidine-induced peripheral neuropathy in this study . The present results suggest that  zimelidine  may be more effective in the treatment of severely depressed patients , rather than those with more mild mixed anxiety/depressive syndromes Although increased pre-treatment severity of depressive symptoms is thought to suggest better outcome with tricyclic antidepressants , it is unclear if such a pattern exists among those depressed patients treated with newer antidepressants . If such a pattern with newer antidepressants were observed , it would have implication s for the design and conduct of future antidepressant trials . We review ed the data from 329 depressed adult patients that were part of 15 multi-center , r and omized , double blind , placebo-controlled antidepressant clinical trials at our center . Based on patients ' pre-treatment scores on the 17-item Hamilton Depression Rating Scale ( HAM-D ) , patients were sub-grouped to one of four severity of depression groups : low moderate , high moderate , moderately severe , and severe . The effect size was 0.51 in the low moderate group , 0.54 in the high moderate group , 0.77 in the moderately severe group and 1.09 in the severe group . An analysis of variance revealed a statistically significant interaction between treatment and severity of depressive symptoms . A correlational analysis revealed that in the group of depressed patients assigned to antidepressants , higher levels of pre-treatment depressive symptoms were significantly associated with greater changes in response to antidepressant treatment . Although a similar pattern was seen among the depressed patients assigned to placebo , it did not reach statistical significance . The results of this study suggest that  antidepressant-placebo differences may be larger among those depressed out patients with higher pre-treatment HAM-D scores compared to those depressed out patients with lower pre-treatment scores . These findings may help in the design of future antidepressant clinical trials This study was design ed to compare the antidepressant effects of alprazolam and amitriptyline in a group of 30 in patients suffering from a severe major endogenous depression , diagnosed by Research Diagnostic Criteria and the Newcastle Rating scale , and to examine the effects of alprazolam and amitriptyline on two biological markers of depression , the dexamethasone suppression test and sleep EEG parameters . The 6-week study was double-blind with a r and om allocation of treatment . Patients were treated with flexible doses of 4 - 9 mg of alprazolam and 100 - 225 mg of amitriptyline . After 4 weeks of treatment the antidepressant effects of amitriptyline significantly exceeded those of alprazolam , as measured on the Hamilton Rating Scale for Depression . There was a high drop-out rate in the alprazolam group because of ineffectiveness of treatment . Alprazolam showed similar effects on sleep parameters as amitriptyline : lengthening of the REM latency and a tendency to shorten stages 3 and 4 and stage REM . These negative clinical results should be interpreted with caution , because of the severity of our selection criteria , and should not be extended to all depressive disorders & NA ; Although amitriptyline relieves pain in many patients with painful diabetic neuropathy , side effects often preclude effective treatment . Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants . We compared a 6 week course of desipramine ( mean dose , 201 mg/day ) to active placebo in 20 patients with painful diabetic neuropathy in a double‐blind crossover trial . Pain relief with desipramine was statistically significant in weeks 5 and 6 . Eleven patients reported at least moderate relief with desipramine , compared to 2 with placebo .  Pain relief tended to be greater in depressed patients , but relief was also observed in patients who did not show an antidepressant effect . We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy , offering an alternative for patients unable to tolerate amitriptyline . Blockade of norepinephrine reuptake , an action shared by desipramine , amitriptyline , and other antidepressants proven effective in neuropathic pain , may mediate this analgesic effect In a double-blind , placebo-controlled study , the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action , amitriptyline and amineptine , was investigated in patients affected by anxious depression . Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder ( DSM-III-R ) and meeting additional operational clinical criteria such as anxiety , trepidation , restlessness , early and /or late insomnia , impulsivity , hostility , dysphoria , compulsivity , hyperperspiration , palpitation , pollakiuria and phobias were included . They were r and omly assigned to three groups ( n = 22 ) and treated either with placebo , amitriptyline ( up to 100 mg/day ) or amineptine ( up to 200 mg/day ) for 6 weeks . Patients showed better response to amitriptyline , a preferential inhibitor of serotonin reuptake , than to amineptine , a selective inhibitor of dopamine reuptake . The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression OBJECTIVE Depression in older adults is often associated with cognitive abnormalities and may predict later development of a primary cognitive disorder . This double-blind , r and omized , placebo-controlled pilot study was design ed to assess the safety and efficacy of galantamine augmentation of antidepressant treatment for depressive and cognitive symptoms in older adults with major depression . METHODS Thirty-eight , non-demented older adults ( age > 50 ) with major depression were r and omized to receive galantamine or placebo augmentation of st and ard antidepressant pharmacotherapy ( venlafaxine XR or citalopram ) .  Mood and cognitive status were monitored for 24 weeks using the 24-item Hamilton Rating Scale for Depression and the Repeatable Battery for the Assessment of Neuropsychological Status . RESULTS Both groups showed significant improvements in mood and cognition over 24 weeks , but no significant difference was found in change over time between groups . An exploratory post-hoc analysis suggested that patients r and omized to galantamine had lower depression scores compared to patients in the placebo group after 2 weeks of treatment . Dropout was high with more subjects r and omized to antidepressant plus galantamine  withdrawing early from the study . CONCLUSIONS This pilot study failed to demonstrate a benefit for galantamine augmentation of antidepressant medication in the treatment of depression in older adults . Future studies should explore strategies for reducing dropout in such longitudinal trials and more carefully assess time to response with cholinesterase inhibitor augmentation Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage In a multicenter series of trials , viloxazine was compared with imipramine , amitriptyline , doxepin and placebo in 123 neurotic and endogenous depressive in patients and out patients . While significant period effects reflecting improvement were obtained on the majority of efficacy variables , no significant differences were obtained among the treatment groups or depressive types . Imipramine and amitriptyline exhibited more anticholinergic adverse reactions ; while , viloxazine exhibited greater CNS effects . Dizziness and nausea were much more frequent in neurotic depressives which may be related to their psychopathology Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients . A column switching technique combined with high performance liquid chromatography ( HPLC ) enabled automated analyses of plasma for simultaneous determination of fluvoxamine , tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run . The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine , clomipramine , amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine . In patients under fluvoxamine monotherapy before comedication , plasma concentrations of fluvoxamine  increased after administration of a tricyclic antidepressant , thus indicating bidirectional drug interactions . The inhibitory effects of fluvoxamine on the metabolism of classical antidepressants disappeared after discontinuation of concomitant fluvoxamine treatment within at least 1–2 weeks . The reported alterations in drug metabolism observed in depressed patients who were under fluvoxamine/tricyclic antidepressant comedication suggested that careful supervision and regular drug monitoring are necessary in such patients A double-blind multicenter evaluation compared the antidepressant efficacy of bupropion ( Wellbutrin ) to both placebo and amitriptyline ( Elavil , Endep ) in adult patients who met DSM-III criteria for major depressive disorder . Steady-state plasma sample s were obtained 11 - 12 hours and 4 hours after the last dose in 50 and 44 patients , respectively , who were treated for 6 weeks with bupropion . There was a curvilinear relationship between antidepressant efficacy and trough plasma bupropion concentrations , with maximum response observed at 5 - 100 ng/ml and virtually none below 25 ng/ml . The increase in plasma bupropion concentration from the trough level to the 4 hour postdose peak level was also positively related to antidepressant response Changes in alpha-2 adrenoreceptor density and affinity during antidepressant treatment were studied using 3H-yohimbine binding to human platelet membranes . Baseline measurements were conducted in 21 patients diagnosed as having major depressive disorder with melancholia , and an equal number of age and sex matched normal controls . No differences were observed in receptor density or binding between pre-treatment subject groups and normal matched controls . Subjects participated for 6 weeks in a trial of placebo , adinazolam , or amitriptyline .  Alpha-2 adrenoreceptor binding was not significantly changed from baseline following antidepressant treatment Thirty newly hospitalized patients with RDC major or minor depressive disorder were r and omly assigned to open treatment according to fixed dosage steps with 1 ) amitriptyline alone , up to a maximum dose of 300 mg/day ; 2 ) tranylcypromine alone , up to a maximum dose of 40 mg/day ; or 3 ) the combination of amitriptyline , up to 150 mg/day , and tranylcypromine , up to 20 mg/day . For 28 patients this protocol continued for 4 weeks or until discharge . As measured by the Hamilton and Zung depression scales , patients in all three treatment groups improved equally . The combination treatment produced a nonsignificantly higher frequency of minor side effects , none of which required discontinuation of treatment . The results indicate the feasibility and safety of further controlled clinical research with combined treatment , although caution is advised Background A number of studies have suggested a link between the patient 's psyche and the course of inflammatory bowel disease ( IBD ) . Although pharmacotherapy with antidepressants has not been widely explored , some investigators have proposed that treating psychological co-morbidities with antidepressants may help to control disease activity . To date a systematic analysis of the available studies assessing the efficacy of antidepressants for the control of somatic symptoms in IBD patients has not been performed . Methods We search ed electronic data bases , without any language restriction . All relevant papers issued after 1990 were examined . Results 12 relevant publications were identified . All of them referred to non-r and omised studies . Antidepressants reported in these publications included paroxetine , bupropion , amitriptyline , phenelzine , and mirtazapine . In 10 articles , paroxetine , bupropion , and phenelzine were suggested to be effective for treating both psychological and somatic symptoms in patients suffering from IBD . Amitriptyline was found ineffective for treating somatic symptoms of IBD . Mirtazapine was not recommended for IBD patients . Conclusion Although most of review ed papers suggest a beneficial effect of treatment with antidepressants in patients with IBD , due to the lack of reliable data , it is impossible to judge the efficacy of antidepressants in IBD . Properly design ed trials are justified and needed based upon the available uncontrolled data & NA ; The efficacy of amitriptyline was evaluated in 28 patients with chronic oral‐facial pain . Most of the patients had evidence of musculoskeletal pain while some had a history suggesting pain of neurogenic origin . Two patients had mixed elements of neurogenic and musculoskeletal pain .  Amitriptyline was more effective than placebo in reducing pain after 4 weeks of treatment . No effect was found after only 1 week of drug administration in either dose range . When the patients were divided into depressed and non‐depressed groups based on their Hamilton depression scores , amitriptyline  reduced pain in the depressed and in the non‐depressed groups as compared to placebo . Amitriptyline  reduced the depression scores in the depressed group but had no effect on the depression scores in the non‐depressed group . Thus , pain reduction was not associated with a change in mood in the non‐depressed group . Amitriptyline had no effect on patients ' ratings of the intensity of experimental heat stimuli . We conclude that amitriptyline is effective in the treatment of chronic oral‐facial pain and that its efficacy is independent of its effects on depression . It appears that tricyclic antidepressants act in a fashion different from opiate drugs that alter the sensory discriminative component of pain Open study Twenty-eight adult patients ( seven males and 21 females ) comparable in terms of age and weight , who had a Hamilton Depression Rating Scale ( HAMD ) score of 18 or more while receiving alternative antidepressants ( mainly amitriptyline : 15 patients ) entered the six-week study without a washout period . All patients received 30 mg paroxetine once daily in the morning , and HAMD scores were measured at the end of weeks 1 , 2 , 4 , and 6 of treatment . Tolerability was also assessed and blood and urine sample s monitored Paroxetine ( 30 mg ) , a selective serotonin ( 5-HT ) reuptake inhibitor , was compared in a double-blind trial to amitriptyline ( 150 mg ) in a sample of 40 in patients aged 18 - 65 years who fulfilled Research Diagnostic Criteria for major depression . Patients were studied after a placebo drug washout period of 10 days and after an active 4-week treatment period . Sleep EEG recordings were performed before and at the end of the study as well as during acute treatment ( first 2 days ) and following withdrawal of active medication . Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile typical of 5-HT reuptake inhibition . Paroxetine and amitriptyline decreased the amount of REM sleep , a well-known effect of classical antidepressants . Paroxetine also shared with other 5-HT reuptake inhibitors an alerting effect on sleep that was not shown to be detrimental on subjective sleep quality BACKGROUND The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy . We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram . However , because a recent meta- analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients , we decided to make an interim analysis . METHOD In patients with medication-resistant major depression we administered in a r and omised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily . After the last rTMS , the patients were followed for another 9 weeks on 20 mg escitalopram daily . The antidepressant effect was measured by the HAM-D(6 ) as primary outcome scale . RESULTS A total of 45 patients with complete data were r and omised so that 23 patients received sham TMS and 22 patients received active , high-frequency rTMS over the left cortex . Over the 3 weeks , the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6 ) above 0.70 , which indicates not only a statistically but also a clinical ly significant effect . The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study . Both the rTMS and escitalopram were well-tolerated . CONCLUSION High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants This paper summarises findings from a study of maintenance treatment in predominantly neurotic depressive responding to initial treatment with amitriptyline . Patients were continued on  amitriptyline  for eight months , withdrawn double-blind to placebo after two months , or withdrawn overtly to no medication , with and without individual psychotherapy from social workers in the factorial design . Continuation significantly reduced early relapse and symptom return , compared with either condition of early withdrawal . Psychotherapy  improved social adjustment after eight months in patients who did not relapse , without any significant interactions . Side effects were minimal , except for carbohydrate craving . These findings suggest that tricyclic antidepressants should be routinely continued for several months after drug-induced remission A comparative age-associated study of the efficacy and side effects of amitriptyline and maprotyline was carried out in a group of 93 patients over 50 . The health status of the patients was assessed with the aid of Hamilton 's depression scale and the scale of side effects on days 0 , 7 and 28 of the therapy . It has been discovered that on day 28 maprotyline caused a more complete reduction of depressive disorders as compared to amitriptyline . Maprotyline produced a more intensive action on the anxious component of depression . There were differences in the intensity and range of side effects evoked by amitriptyline and maprotyline . Unlike maprotyline , the antidepressive effect of amitriptyline developed in a group of patients over 70 , at later stages of the therapy . Therefore , it is more advisable that tetracyclic antidepressants be used for the treatment of senile patients 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 Major depression is associated with an increased risk for myocardial infa rct ion . Adipokines have been shown to link obesity with metabolic disturbances . Based on this finding the present study was design ed to investigate the effect of antidepressive treatment with either amitriptyline or paroxetine on circulating concentrations of resistin and adiponectin in depressed patients , and to establish , whether these adipokines are associated with the activation of the hypothalamic-pituitary-adrenal (HPA)-system . Thirty-seven depressed in- patients were treated in a double-blind , r and omized protocol with either amitriptyline or paroxetine over a period of five weeks . After six drug free days blood was drawn on day 1 and again 36 days after antidepressive treatment for the measurement of resistin and adiponectin , fasting glucose and insulin concentrations . For quantification of free cortisol levels saliva was obtained daily at 0800 hours during weeks 1 and 5 . While resistin concentrations decreased in patients remitting under amitriptyline and paroxetine ( p<0.03 ) , no changes were observed in non-remitters . At baseline , though not during treatment , circulating resistin concentrations correlated positively with free cortisol levels and with BMI ( p<0.01 ) . Adiponectin levels , however , did not change during treatment and were not associated with free cortisol concentrations but were instead positively related to QUICKI ( p<0.03 ) . In conclusion , the present data revealed resistin but not adiponectin to be related to free cortisol concentrations and to decline in remitters to antidepressive treatment INTRODUCTION : Long-term exposure to antidepressants is required to prevent relapses and recurrences in patients with recurrent major depression . Furthermore , a good pharmacological compliance is the key to successful long-term treatment . Since the early phases of a treatment influence long-term compliance and compliance is adversely affected by poorly tolerated treatments , efficacy and tolerability of paroxetine and amitryptiline over 12 weeks were compared as an introduction to the issue of long-term compliance to these two agents . METHOD : A 12-week , r and omized , double-blind , doubledummy , parallel-group trial which involved 129 patients with recurrent major depression . RESULTS : Both paroxetine and amitriptyline were effective in controlling the symptoms of depression , as shown by the reduction in HAMD total score and CGI severity-of-illness score at endpoint compared to baseline . There was no statistically or clinical ly significant difference between the two treatments in terms of efficacy . However , marked numerical differences were noted in tolerability : the percentage of patients who reported treatment-emergent adverse experiences was greater in the amitriptyline group ( 40.0 % vs 28.1 % ) . This difference was mainly due to anticholinergic adverse events , which were six times more frequent with amitriptyline than with paroxetine . CONCLUSION : When compared with amitriptyline , paroxetine should allow patients with recurrent major depression to receive an equally effective treatment with a relatively lower incidence of adverse experiences Background : the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre , r and omized , double-blind , amitriptyline-controlled , 5 week clinical study . Method : 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression ( HPRSD ) score ≥ 18 , were r and omized to treatment with either mirtazapine  20 - 60 mg/day or amitriptyline  75 - 225 mg/day . Results : mirtazapine and amitriptyline were equally effective in reducing depressive symptoms , as assessed by the 17-item HPRSD and MADRS scales . Mirtazapine was better tolerated than amitriptyline , with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial . Conclusion : this study shows that mirtazapine is as effective as amitriptyline in treating major depression , while at the same time better tolerated Fifty-eight actively psychotic in patients who initially met criteria for long-st and ing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder ( mainly schizophrenic ) with a depressive syndrome , and who scored at least 30 ( mean = 55 , SEM = 1.6 ) on the Brief Psychiatric Rating Scale and 17 ( mean = 23 , SEM = 0.7 ) on the Hamilton Rating Scale for Depression , were treated for 5 weeks with haloperidol hydrochloride and benztropine . Haloperidol and benztropine treatment was continued , while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were r and omly assigned to the following double-blind treatment groups for 4 weeks : adjunctive amitriptyline hydrochloride , desipramine hydrochloride , or placebo . Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage , when compared with haloperidol and placebo , on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression . After 4 weeks of combine therapy , patients receiving adjunctive amitriptyline or desipramine , as compared with those receiving adjunctive placebo , tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo . These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic in patients .  Adjunctive antidepressants may retard the rate of resolution of psychosis in this population Patients with anorexia nervosa have concurrent problems of emaciation and depression . Therefore , treatment with medications affecting both weight gain and depression seemed reasonable . Seventy-two anorectic patients were r and omly assigned in a double-blind study to receive cyproheptadine hydrochloride , a weight-inducing drug , amitriptyline hydrochloride , a tricyclic antidepressant , or placebo . Overall , cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight . There was a differential drug effect present in the bulimic subgroups of the anorectic patients : cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups . The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups . Cyproheptadine had an anti-depressant effect demonstrated by a significant decrease in the Hamilton depression ratings Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors . The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine . However , most data were collected in sample s of out patients . To overcome this restriction , a six-week double-blind control-group study , comparing 30 mg paroxetine with 150 mg amitriptyline per day , was performed in a sample of in patients suffering from major depression . Generally speaking , the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline , either with respect to the total score on the Hamilton Depression Scale ( HAMD ) and the Clinical Global Impressions or with respect to the subscores of the HAMD . One exception was the retardation subscore , in which amitriptyline showed a greater degree of reduction . Both drugs had a characteristic side-effect profile .  Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea Diagnostic criteria , r and om parallel placebo-controlled study design , and appropriate clinical assessment for both safety and efficacy are all among the essential requirements for the evaluation of a new antidepressant agent . Paroxetine and imipramine were compared for efficacy and safety in a large multicentre , r and omized , placebo-controlled , double-blind , parallel design study in the USA . The study involved 717 out patients with major depressive disorder ; after a one-week washout period they were treated for 6 weeks , being assessed at weekly intervals . The results from all six participant centres combined showed that both active drugs were statistically superior to placebo by week 2 and that the antidepressant response was significant for both . Paroxetine was better tolerated than imipramine with fewer dropouts from side effects . This combined study clearly indicated that paroxetine was an effective and well-tolerated antidepressant Forty-two patients with depression and epilepsy were entered into an antidepressant trial of amitriptyline , nomifensine and placebo . The dose of the active drug was 25 mg tid , which was doubled in non-responders on the active drug after 6 weeks . At that point a further 6 week follow-up was carried out . Serum antidepressant and anticonvulsant levels were assessed . The results indicated that at 6 weeks all patients showed a decline in their depression scores but at 12 weeks nomifensine was superior to amitriptyline . The possible reasons for this and the clinical implication s of this are discussed In a small study of up to 3 years ' duration comparison of the value of amitriptyline alone versus amitriptyline + lithium in unipolar cases ( 27 patients ) and of that of lithium alone versus amitriptyline + lithium in bipolar cases ( 13 patients ) showed no advantage for the combination treatments in terms of efficacy in reducing depressive relapses . There was no effect of treatment , developing depression or developing hypothyroidism upon the psychological tests which were conducted during this prolonged study . Observer and self ratings detected an increase in depression before relapse was clearly present , but of the various psychological assessment s conducted only arousal showed changes in association with developing and definite relapse . The prescription of lithium but not amitriptyline + lithium or amitriptyline alone was associated with significant increases in blood pressure Efficacy Although clinicians often view MAOIs as more difficult to prescribe than agents in other classes , there is little doubt about their efficacy . In bipolar depression , for example ( where impactful treatments are few and far between ) , response rates with tranylcypromine have been reported to exceed 80 % , and this agent may be more efficacious than TCAs such as imipramine , particularly in patients with anergic , motor-retarded features.4 MAOIs also may yield better antidepressant efficacy than TCAs in chronic depression and dysthymia.5 In refractory major depression , response rates of at least 40%–50 % have been reported for both tranylcypromine and phenelzine , with comparable head-to-head efficacy.6 It was therefore surprising that , in the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) trials , patients r and omly assigned to tranylcypromine ( a fourth-level intervention following nonresponse to an SSRI and 2 other interventions ) obtained a meager 6.9 % remission rate.7 However , low mean dosing of tranylcypromine in that study ( < 40 mg/d ) quite likely underestimated optimal MAOI benefits for advanced forms of treatment-resistant depression . Studies from the 1970s and 1980s made MAOIs virtually synonymous with treatment for atypical depression , with reports of superiority to TCAs ( review ed by Henkel et al8 ) . MAOIs are also often thought of for anxious depression on the basis of an older literature comparing phenelzine with tricyclics such as amitriptyline.9,10 Much of this literature focused on pre – DSM-III constructs such as “ neurotic ” or “ reactive ” depressions that may also relate to atypical depression . Excitement surrounding such apparent differential therapeutics was largely dissipated by the rapid ascension of SSRIs , which essentially replaced TCAs as the antidepressants of first choice by the early 1990s . Whereas MAOIs were clearly superior to TCAs , there was little reason to view them as superior to SSRIs , which were substantially safer Background and aims : Irritable bowel syndrome ( IBS ) is a disorder of intestinal hypersensitivity and altered motility , exacerbated by stress . Functional magnetic resonance imaging ( fMRI ) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex ( ACC ) , an area relevant to pain and emotions . Tricyclic antidepressants are effective for IBS . The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits . Secondary aims were to identify other brain regions altered by amitriptyline , and to determine if reductions in cerebral activation are greater during mental stress . Methods : Nineteen women with painful IBS were r and omised to amitriptyline 50 mg or placebo for one month  and then crossed over to the alternate treatment after washout .  Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI . Distensions were performed alternately during auditory stress and relaxing music . Results : Rectal pain induced significant activation of the perigenual ACC , right insula , and right prefrontal cortex . Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex , but only during stress . Conclusions : The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual ( limbic ) anterior cingulated cortex and parietal association cortex . These reductions are only seen during stress . Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors ( SSRIs ) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity . The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan ( 200 mg , L-5-HTP ; PO)–induced increases in plasma cortisol and prolactin ( PRL ) concentrations were studied in patients with major depression or obsessive compulsive disorder ( OCD ) . Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD . The  L-5-HTP – induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients . The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP . The L-5-HTP – induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different . The results suggest that fluoxetine , but not tricyclic antidepressants , potentiates 5-HT receptor – mediated stimulation of cortisol and PRL secretion in humans , consistent with available evidence that fluoxetine treatment , but not tricyclic antidepressants , increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism In the context of chronic physical illness , such as breast cancer , depression is associated with increased morbidity , longer periods of hospitalization , and greater overall disability . Prompt diagnosis and effective treatment is , therefore , essential . Several small studies have established the efficacy of tricyclic antidepressants ( TCAs ) in this setting , and the selective serotonin reuptake inhibitors ( SSRIs ) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile . This was a multicenter , double-blind , parallel-group study in which 179 women with breast cancer were r and omized to treatment with either the SSRI paroxetine ( 20–40mg/day ) , or the TCA , amitriptyline ( 75–150mg/day ) . After 8-weeks treatment , depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale . Clinical global impression ( CGI ) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint ; a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale . A steady improvement in quality of life was also observed in both groups . There were no clinical ly significant differences between the groups . In total , 47 ( 53.4 % ) patients in the paroxetine group and 53 ( 59.6 % ) patients in the amitriptyline group had adverse experiences , the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy . Anticholinergic effects were almost twice as frequent in the amitriptyline group ( 19.1 % ) compared with paroxetine ( 11.4 % ) . This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer Thirty-two patients who had responded to amitriptyline ( 150 mg daily ) when suffering from a depressive illness were allocated either to receive placebo or to remain on the same medication for one year . Plasma concentrations of the drug were regularly estimated . There was no correlation between plasma concentration and subsequent residual affective morbidity . In spite of considerable encouragement , three of the patients did not take the prescribed amitriptyline and they all relapsed . Five out of sixteen patients who received placebo  relapsed . None of the patients who continued to take amitriptyline  relapsed . It is emphasized that the patients studied were selected , inasmuch as they were apparent responders to amitriptyline . It is concluded that this group of patients should continue to be treated with antidepressant medication for eight months after apparent recovery , and care should be taken to ensure the patients ' compliance Summary : To establish the differential indication of trazodone and to find the predictors of its efficacy , we conducted a study in which 45 patients with major depressive disorder and 75 patients with acute schizophrenia were r and omly assigned under double‐blind conditions to either 400 mg trazodone daily , 150 mg amitriptyline daily , 20 mg haloperidol daily , or placebo daily . At the beginning of the investigations , numerous variables ( basic data , MMPI , AMDP , HAM‐A , HAM‐D ) were documented and evaluated on days 3 , 7 , 14 , and 21 . In our study , trazodone proved to be as effective an antidepressant drug as amitriptyline . In group comparison , no antipsychotic action of trazodone in schizophrenic patients could be proved . Yet the trazodone treatment was clearly of less risk than the amitriptyline treatment . Under trazodone , provocation of schizophrenic symptoms , which occurred numerously under amitriptyline , was found only in one patient out of 17 schizophrenics . Related to anamnesis and characteristics of the schizophrenic patient , a predictor‐variable concerning the antipsychotic effect was not found . It can be assured , however , that patients with depressive symptoms  ( regarding the entity classification ) respond to trazodone . After only 7 days of trazodone treatment , a relatively reliable decision can be established as to whether a therapeutical success can be expected if treatment is continued The tricyclic antidepressant drug amitriptyline was evaluated as a short-term treatment of anorexia nervosa patients . In a 5-week double-blind , placebo-controlled study 11 patients were given amitriptyline and 14 received placebo .  In addition , 18 patients who refused to participate in the drug trial and received only psychosocial treatment were used as an additional comparison group . Overall , patients in the three groups showed little improvement . No statistically significant differences favoring amitriptyline were found in any of the outcome variables . Plasma levels varied widely among patients receiving similar doses . No association was found between plasma levels and improvement in either psychiatric symptomatology or weight .  Amitriptyline patients did not manifest any tendency for a reduction of depressive symptomatology . In addition , amitriptyline treatment was associated with substantial discomfort and adverse affects Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressant agents , but its pain-relieving potential has received little study . Other antidepressant agents -- notably amitriptyline -- are known to ameliorate postherpetic neuralgia , but those agents are often toxic . In a r and omized double-blind crossover design , we gave 26 postherpetic neuralgia patients 6 weeks of treatment with desipramine ( mean dose , 167 mg/day ) and placebo .  Nineteen patients completed both treatments ; 12 reported at least moderate relief with desipramine and two reported relief with placebo .  Pain relief with desipramine was statistically significant from weeks 3 to 6 . Psychiatric interview at entry into the study produced a diagnosis of depression for 4 patients ; pain relief was similar in depressed and nondepressed patients and was statistically significant in the nondepressed group alone . We conclude that desipramine administration relieves postherpetic neuralgia and that pain relief is not mediated by mood elevation . Blockade of norepinephrine reuptake , an action shared by desipramine , amitriptyline , and other antidepressant agents that have relieved neuropathic pain , may be involved in relief of postherpetic neuralgia A double blind comparison is reported of a new tetracyclic antidepressant , maprotiline , with amitriptyline and placebo in psychiatric out patients .  Amitriptyline was significantly more effective than placebo in its global effect on depression .  Maprotiline emerged as neither inferior to amitriptyline nor superior to placebo . Method ological difficulties prevented an adequate assessment of the anxiolytic activity of maprotiline The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram , in the treatment of major depressive disorder ( MDD ) . In total , 357 out patients with MDD were r and omized to treatment with reboxetine 8 - 10 mg or citalopram 20 - 40 mg per day during 24 weeks . Primary end-point was change from baseline in the Hamilton Depression Rating Scale ( HAM-D , 21 items ) . Sexual function/dysfunction was measured by the Sexual Function scale ( SF ) . Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores : reboxetine with -21.4 and citalopram with -22.1 points ( NS ) . LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine ( -19.6 vs. -17.8 ; P = 0.034 ) . The response rate was 90.3 % for reboxetine and 92.7 % for citalopram ( NS ) . The most common side effect in the reboxetine group was dry mouth , and in the citalopram group sexual dysfunction . At week 24 , anorgasmia was reported by 5.9 % of the sexually active women in the reboxetine group vs 39 % in the citalopram group . The  dropout number  was 91 in the  reboxetine group , and 54 in the citalopram group . To summarize , both treatments gave a satisfactory antidepressant effect . The side effect profile differed between the groups , with a notably high prevalence of sexual dysfunctions in the citalopram group . The high number of dropouts in the reboxetine group , is considered as a result of the non-titration starting dose of 8 mg reboxetine per day , which gave a high incidence of early side-effects .  Depressive disorders including major depression ( MDD ) is very common , with a lifetime prevalence of at least 15 % in men and 25 % in women.1,2 Depression can be treated effectively by a range of antidepressant agents . Recent review s have suggested that the selective serotonin reuptake inhibitors ( SSRIs ) offer equal efficacy to the older antidepressant agents , such as tricyclic antidepressants , with the advantage of greater tolerability.3 - 5 Other review ers have reported that non-SSRI antidepressants , such as clomipramine , have been found to be significantly more effective than fluoxetine for the treatment of patients with severe depression.6  Reboxetine ( reboxetine mesylate , Edronax ; Pfizer , New York ) is a highly selective noradrenaline reuptake inhibitor , and the efficacy of reboxetine has been independently demonstrated in multiple r and omized , double-blind , placebo-controlled studies .7 - 9 In addition to improvements in depressive symptoms , treatment-associated improvements in social behavior ( measured using the Social Adaptation Self-evaluation Scale [SASS]),10 were noticed in one of these studies .8 In this study , reboxetine was statistically and clinical ly superior to both placebo and fluoxetine in improving social functioning . The primary objective of the current study was to assess efficacy and tolerability of reboxetine  in comparison with those of citalopram ( Cipramil ; H. Lundbeck , Copenhagen , Denmark ) in patients with MDD .  Citalopram is a highly SSRI . The antidepressant mechanism is presumed to be a result of stimulation of serotonergic neurotransmission in the central nervous system as a consequence of higher serotonin levels result ing from inhibition of the serotonin transporter . The therapeutic efficacy of citalopram in patients with MDD has been investigated in several placebo-controlled studies and in long-term and extension studies .11 The underlying rationale for this comparison was to study 2 different drug profiles , 1 drug being pure " adrenergic " and the other pure " serotonergic . " A secondary objective was to analyze the correlation between the types of depression ( ie , degree of melancholia and the efficacy of the 2 drugs ) SUMMARY The antidepressant efficacy and safety of milnacipran , a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline , was compared with that of the tricyclic antidepressant , imipramine , in a multi-centre , double-blind , r and omised , parallel group , comparative trial in 5 hospital centres in Spain . One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association ( third revision ) , with a minimum score of 25 on the Montgomery and Åsberg Depression Rating Scale were treated for 6 weeks with milnacipran ( 100 mg/day ) or imipramine ( 150 mg/day ) . Both treatments showed similar efficacy in reducing depressive symptoms . The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group , particularly those related to anticholinergic symptoms . Dysuria and shivering , however , were more common with milnacipran . The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine The objective of this study was to determine the relative efficacy and safety of fluoxetine and amitriptyline in the treatment of major depression complicating Alzheimer 's disease ( AD ) . The sample included 37 patients with AD and major depression . The study design was a double-blind , fixed-dose , r and omized clinical trial with 45 days of follow-up . The outcome measures were the Hamilton Depression Rating Scale ( Ham-D ) , the Mini-Mental State Exam ( MMSE ) , and the number of dropouts from each arm of the study . Efficacy was similar for fluoxetine and amitriptyline . At Day 45 , there was a mean 9.4-point reduction in Ham-D scores ( t[df,62 ] = 9.68 , P < 0.0001 ) and a 2.4-point mean increase in MMSE scores as compared to baseline ( t[df,2 ] = 2.69 , P = 0.009 ) . Eleven ( 58 % ) of the amitriptyline-treated patients dropped out , compared with 4 ( 22 % ) of the fluoxetine-treated patients ( chi 2[df,2 ] = 8.9 , P = 0.017 ) . The authors conclude that antidepressant treatment for major depression complicating AD is effective . While fluoxetine and amitriptyline are equally effective , fluoxetine is better tolerated The authors compared the nontricyclic antidepressant trazodone with amitriptyline and placebo in a double-blind study of 202 unipolar depressed out patients .  Trazodone 's clinical efficacy was similar to that of amitriptyline , with both active drugs producing significantly more clinical improvement than placebo . The incidence of anticholinergic side effects was lower for the patients taking trazodone than for those taking amitriptyline OBJECTIVE To compare the efficacy and tolerability of paroxetine ( a selective serotonin reuptake inhibitor ) with that of amitriptyline ( a tricyclic antidepressant ) in the treatment of depression in 191 patients with rheumatoid arthritis ( RA ) . METHODS A r and omized , double blind , double dummy , parallel group study . A placebo washout period of 3 - 7 days was followed by an 8 week active treatment phase during which patients received either paroxetine ( 20 - 40 mg daily ) or amitriptyline ( 75 - 150 mg daily ) . The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint . RESULTS Paroxetine was as effective as amitriptyline for the treatment of depression , with similar improvements in RA associated pain and disability also seen in both groups . However , paroxetine was better tolerated than amitriptyline , with an overall frequency of adverse experiences of 56.4 % and 67.7 % in the 2 groups , respectively . The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group ( 18.1 % vs 43.8 % taking amitriptyline ) and paroxetine treated patients also experienced fewer severe ( 16.0 % vs 21.9 % ) , serious nonfatal ( 0 % vs 4.2 % ) , and drug related adverse experiences ( 12.8 % vs 29.2 % ) . CONCLUSION Tolerability is an important consideration in this patient population , which is largely composed of elderly patients who are taking additional medications for RA .  Paroxetine shows a number of advantages in the management of depression comorbid with RA BACKGROUND Previous studies indicate that depressed patients with partial remission and residual symptoms following antidepressant treatment  are common and have high rates of relapse . There is evidence that cognitive therapy may reduce relapse rates in depression . METHODS One hundred fifty-eight patients with recent major depression , partially remitted with antidepressant treatment ( mean daily doses equivalent to 185 mg of amitriptyline or 33 mg of fluoxetine ) but with residual symptoms of 2 to 18 months ' duration , were included in a controlled trial . Subjects were r and omized to receive clinical management alone or clinical management plus cognitive therapy for 16 sessions during 20 weeks , with 2 subsequent booster sessions . Subjects were assessed regularly throughout the 20 weeks ' treatment and for a further year . They received continuation and maintenance antidepressants at the same dose throughout . RESULTS Cognitive therapy reduced relapse rates for acute major depression and persistent severe residual symptoms , in both intention to treat and treated per protocol sample s. The cumulative relapse rate at 68 weeks was reduced significantly , from 47 % in the clinical management control group to 29 % with cognitive therapy ( hazard ratio 0.54 ; 95 % confidence interval , 0.32 - 0.93 ; intention to treat analysis ) . Cognitive therapy also increased full remission rates at 20 weeks but did not significantly improve symptom ratings . CONCLUSION In this difficult-to-treat group of patients with residual depression who showed only partial response despite antidepressant treatment , cognitive therapy produced worthwhile benefit In a prospect i ve , controlled , double-blind study , 37 patients with major depressive disorder were subclassified into primary depression ( N = 25 ) and secondary ( N = 12 ) depression and treated with either amitriptyline ( primary depressives N = 13 , secondary depressives N = 6 ) or bupropion ( primary depressives N = 12 , secondary depressives N = 6 ) . A differential response to the novel antidepressant bupropion  was observed between the two diagnostic subgroups , but no differential response to amitriptyline  was observed ; patients with primary depression and secondary depression responded equally well to  amitriptyline  but not to  bupropion .  Our results provide pharmacological evidence supporting the usefulness of this subclassification of depression A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran ( 50 mg and 100 mg/day ) and amitriptyline ( 150 mg/day ) in three parallel groups of 45 major depressive in patients defined by Research Diagnostic Criteria . After a wash-out period of 4–7 days on placebo with lorazepam and /or nitrazepam if necessary , patients were r and omly assigned to a daily dose of milnacipran 50 mg , milnacipran 100 mg or amitriptyline 150 mg reached on the 5th day and then stable over a 4-week period , with weekly assessment s by means of the Montgomery and Asberg depression scale , the Hamilton depression scale , the Clinical Global Impressions ( CGI ) and the Target Emergent Signs and Symptoms . Results showed significant superiority of both milnacipran 100 mg/day and amitriptyline over milnacipran 50 mg/day at the end of the treatment period . However , amitriptyline induced a nonsignificant trend toward more rapid improvement after 2 weeks of treatment , mainly based on items related to insomnia , supporting more sedative properties of amitriptyline as compared to milnacipran . Anticholinergic side-effects were significantly lower with milnacipran than with amitriptyline , explaining why milnacipran 100 mg exhibited at the end of the treatment period , a nonsignificantly better efficacy index on the CGI . Moreover , in contrast to milnacipran , amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain The authors conducted a double-blind , placebo-controlled clinical trial of the selective 5-HT reuptake inhibitor zimelidine in the treatment of major depressive illness .  Zimelidine had the same antidepressant efficacy as amitriptyline but significantly fewer side effects , especially anticholinergic effects Improvements of individual depressive symptoms in patients with depression was compared between those treated with tricyclic antidepressants ( TAD ) and those treated with other psychoactive drugs or placebo . In the majority of comparisons , patients did not improve significantly more with TAD than with other drugs or placebo . These findings indicated that tricyclic antidepressants are not useful in the treatment of most patients with depression . Despite our findings , it is realized that a minority of patients with depression may benefit by treatment with tricyclic antidepressants Patients and methods Male and female patients diagnosed as having a major episode of depression according to DSM-111 criteria , and who had aminimum score of 18 on the 21-item Hamilton Depression Rating Scale ( HAMD ) , were eligible for entry into the study . Pregnant or lactating women , patients with severe co-existing diseases , known alcohol abusers , and those known to be intolerant of tricyclic antidepressants were excluded Abstract Antidepressant drugs are increasingly used in the management of  chronic pain .  They are mainly prescribed for cancer‐related pain and central pain , e.g. phantom or stump pain , post‐herpetic neuropathy . However , no controlled clinical trials have vali date d their in either pathology . Thus , physicians still do not know whether antidepressants are really effective and which might be best . It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself . To verify both the analgesic effect of tricyclic antidepressants , and the possible relationship between their antidepressant effect and the relief of central pain , we carried out a r and omized , within‐patient ( cross‐over ) placebo‐controlled study in patients suffering from central pain . The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo ( p < 0.0001 ) . Within the antidepressants tested , chlorimipramine , a blocker of serotonin reuptake , is significantly more effective ( p < 0.0001 ) than nortriptyline , a blocker of noradrenaline reuptake . Finally , the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression
Amitriptyline is an efficacious antidepressant drug .
It is , however , also associated with a number of side effects .
Degree of placebo response and severity of depression at baseline may moderate drug-placebo efficacy differences
BACKGROUND Amitriptyline is a tricyclic antidepressant that was synthesis ed in 1960 and introduced as early as 1961 in the USA , but is still regularly used .
It has also been frequently used as an active comparator in trials on newer antidepressants and can therefore be called a ' benchmark ' antidepressant .
However , its efficacy and safety compared to placebo in the treatment of major depression has not been assessed in a systematic review and meta- analysis .
OBJECTIVES To assess the effects of amitriptyline compared to placebo or no treatment for major depressive disorder in adults .