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.
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
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 .