A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression. A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial. Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. Symptom relief with amitriptyline in the irritable bowel syndrome. Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Combination tricyclic antidepressant and lithium maintenance medication in unipolar and bipolar depressed patients. The analgesic effect of amitriptyline on chronic facial pain A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. [Comparative study of age-related effectiveness of tri- and tetracyclic antidepressants]. A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression.
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 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 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 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 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 Patients ( n = 150 ) were r and omized to a 6-week , double-blind study to evaluate the relative efficacy and safety of mirtazapine , amitriptyline , and placebo in the treatment of major depressive disorder symptoms . Average daily modal doses were mirtazapine , 18 mg ; amitriptyline , 111 mg ; and placebo , 4.6 capsules . Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression ( HAM-D ) score reductions ( weekly visits 1 , 2 , 4 , and endpoint ) compared to placebo . These findings were supported by the Montgomery-Asberg Depression Rating Scale ( MADRS ) ; the Zung Self-rating Depression Scale ( SDS ) ; and the Clinical Global Impressions ( CGI ) scales . Somnolence and weight gain were the only adverse clinical experiences ( ACEs ) reported substantially more often by mirtazapine-treated patients than by those in the placebo group . However , more amitriptyline-treated patients reported decreased visual accommodation , dry mouth , dyspepsia , constipation , tachycardia , hypertension , hypotension , discoordination , dizziness , and tremor than mirtazapine- or placebo-treated patients . Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients , and superior to amitriptyline in respect to anticholinergic and cardiovascular effects 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 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 Anti-depressants have been reported to be useful in the management of the  Irritable Bowel syndrome .  We studied the efficacy of amitriptyline for 12 weeks in a r and omized double-blind placebo-controlled trial . Forty patients who met predefined criteria entered the trial . They received 25 mg amitriptyline for the first week , 50 mg for the second week and 75 mg nightly thereafter until the end of the 12th week . The drug and placebo groups were comparable in all major pretreatment variables . Amitriptyline was found to be significantly more effective than placebo in producing global improvement , increasing feelings of well-being , reducing abdominal pain and increasing satisfaction with bowel movements . Younger age and increasing extroversion predicted a better response to amitriptyline .  Severity of depressive and anxiety symptoms and other personality variables did not influence outcome We are performing a double-blind trial with inward psychiatric patients . The indication for our psychotropic or psychotherapeutic intervention is mainly severe depression ( = major depressive disorders DSM III ) . For a 3-week trial course trazodone ( 400 mg daily ) , amitriptyline ( 150 mg/die ) or placebo capsules were given at r and om . All patients received the same type of cognitive behaviour therapy . The test battery consists of CGI , BPRS , HAMD , HAMA and AMDP ; adverse drug reactions are documented as “ free reports ” ( = freier Nebenwirkungsbericht ) . The interim results ( until March 1987 ) will be presented . Our investigation indicates that it is probable that the trazodone treatment we used is equivalent to corresponding amitriptyline treatment 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 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 & 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 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 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 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
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 .