title: Treatment of depression by drugs and psychotherapy. Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression PREDICTORS OF RESPONSE TO AMITRIPTYLINE AND PLACEBO IN THREE OUTPATIENT TREATMENT SETTINGS Experimental Examination of Trazodone Relationship between response to phenelzine and MAO inhibition in a clinical trial of phenelzine, amitriptyline and placebo. A double-blind non-crossover placebo-controlled study between group comparison of trazodone and amitriptyline on cardiovascular function in major depressive disorder. Controlled Trial of Amitriptyline in General Practice A controlled study of mianserin in moderately to severely depressed outpatients. Treating the depressed elderly patient: the comparative behavioral pharmacology of mianserin and amitriptyline. Drugs in Depressive Illness CLINICAL RESPONSE TO AMITRIPTYLINE AMONG DEPRESSED WOMEN High incidence of multisystemic reactions to zimeldine The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo. A collaborative study of a new antidepressant, viloxazine, in neurotic and endogenous depressives. A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness Mirtazapine versus amitriptyline in the long‐term treatment of depression: a double‐blind placebo‐controlled study Zimeldine tolerability in comparison to amitriptyline and placebo: findings from a multicentre trial A controlled trial of maprotiline (Ludiomil) in depressed outpatients. Physician prognosis in relationship to drug and placebo response in anxious and depressed psychiatric outpatients. Amoxapine and amitriptyline Lithium as a prophylactic agent in unipolar affective illness: comparison with cyclic antidepressants. A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression. Amitriptyline in anxious-depressed outpatients: a controlled study. Antidepressant response and plasma concentrations of bupropion. PREDICTORS OF AMITRIPTYLINE RESPONSE IN OUTPATIENT DEPRESSIVES Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. Effect of tricyclic antidepressants on individual symptoms. The Family of the Asthmatic Child* Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant Amoxapine and amitriptyline Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo Severity of unipolar depression and choice of treatment. Comparative effects of amitriptyline and amineptine in patients affected by anxious depression. A double‐blind, placebo‐controlled study comparing mianserin and amitriptyline in moderately depressed outpatients Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. Outcome profiles in the treatment of unipolar depression. Predictors of treatment outcome for major depression in primary care. Demography, auxology and response to recombinant human growth hormone treatment in girls with Turner's syndrome in the Kabi Pharmacia International Growth Study Controlled trial of zimelidine, a 5-HT reuptake inhibitor, for treatment of depression. Weight changes in antidepressants: a comparison of amitriptyline and trazodone. Amitriptyline, clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. Clovoxamine in the treatment of depressed outpatients: a double-blind, parallel-group comparison against amitriptyline and placebo. Social skills training compared with pharmacotherapy and psychotherapy in the treatment of unipolar depression. Are antidepressants better than placebo? Cianopramine and amitriptyline in the treatment of depressed patients — a placebo-controlled study Comparison of the electrocardiographic effect of dothiepin and amitriptyline. A double-blind comparison of dothiepin and amitriptyline for the treatment of depression with anxiety Differential effect of amitriptyline and bupropion on primary and secondary depression: a pilot study. A controlled comparison of amitriptyline and electroconvulsive therapy in the treatment of depression. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Nonspecific factors and side effect complaints: FACTORS AFFECTING THE INCIDENCE OF DROWSINESS IN DRUG AND PLACEBO TREATED ANXIOUS AND DEPRESSED OUTPATIENTS Response to phenelzine and amitriptyline in subtypes of outpatient depression. Fluoxetine in tricyclic refractory major depressive disorder. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. Thyroid functioning during treatment for depression. Changes in Weight During Treatment for Depression Verapamil in affective disorders: A controlled, double-blind study Interaction of drug therapy with marital therapy in depressive patients. Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Platelet alpha-2 adrenoreceptor activity pre-treatment and post-treatment in major depressive disorder with melancholia. A clinical assessment of a sustained release preparation of amitriptyline. An evaluation of alprazolam in the treatment of reactive or neurotic (secondary) depression. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. Placebo response rates in psychotic and nonpsychotic depression. Stimulus Intensity Control in Depression: A Study of the Comparative Effect of Doxepin and Amitriptyline on Cortical Evoked Potentials A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicentre study
abstract: Prevention of relapse following depression is a pressing research problem . The authors tested the efficacy of the tricyclic antidepressant amitriptyline and psychotherapy , alone and in combination , in preventing the relapse of 150 neurotic depressed female patients . They found that patients receiving amitriptyline and little psychotherapy had a 12-percent relapse rate , compared to a 16-percent rate for those receiving more psychotherapy and no medication . There was no significant difference between drug therapy alone or drug therapy in combination with psychotherapy . However ,  psychotherapy was beneficial to patients with problems of social adjustment and interpersonal relations .  The need for further research and implication s for treatment are discussed Adinazolam , a triazolobenzodiazepine , was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives . Forty-eight patients entered the study , and 35 completed 6 weeks of evaluation . Patients were well matched in each of the groups . Initially , the adinazolam group showed more improvement than the placebo group , but this trend did not persist beyond day 7 . The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups , and final scores were significantly better for amitriptyline . Depressive symptoms in the amitriptyline dropout group appeared improved , whereas in the adinazolam and placebo dropout groups they were unchanged or worse . Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo . Thus , amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo The present report examines the predictors and modifiers of response to amitriptyline in an effort to : identify variables whose effects on drug response are general enough to apply to a range of patient types and treatment setting s , isolate predictors , and evaluate the extent to which contrasting conditions across treatment setting s may lead to contrasting predictors of treatment effects . The sample comprised moderately depressed neurotic out patients from three treatment setting s : 84 clinic patients from an outpatient clinic in a city hospital , 95 patients from the private practice of general practitioners , and 78 patients from the private practice of a group of psychiatrists . Potential predictors from which regressors in a step search multiple regression procedure could be selected were : patient demographic and attitudinal characteristics , assessment s of presenting illness and its history , and evaluations of aspects of the patient-therapist interaction 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 This report examines the hypothesis that for phenelzine to be more effective than placebo it is necessary to achieve at least 80 % inhibition of platelet MAO activity . This hypothesis was examined in the context of a double-blind comparison of phenelzine , amitriptyline and placebo in depressed patients . When phenelzine became significantly more effective than placebo at 4 weeks , the average MAO inhibition was 85 % . By the 5th week , with MAO inhibition greater than 90 % , phenelzine was significantly more effective than amitriptyline . A highly significant correlation was noted between improvement and MAO inhibition within the phenelzine group The cardiovascular effects of trazodone ( TZD ) , amitriptyline ( AMT ) and placebo were studied in out- patients with major depression .  AMT was shown to have the expected effects on the electrocardiograph and on systolic time intervals consistent with its proven anticholinergic and quinidine-like properties . TZD , in contrast , had no quinidine-like effects and minor effects on systolic time intervals . However , it was not without any cardiovascular effects . Although TZD was shown to be a safer preparation than the reference drug AMT , long-term monitoring is needed to explain the minor effect on heart rate and T wave changes A controlled double-blind trial of amitriptyline at two dosage levels ( 75 and 150 mg/day ) , amylobarbitone ( 150 mg/day ) , and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness . Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups . Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety . Troublesome side effects were equally distributed among the four treatments Following a 1-week , single-blind placebo washout , 150 patients were r and omized to double-blind treatment with daily doses of either mianserin  , 30 mg to 150 mg ;  amitriptyline , 60 mg to 300 mg ; or placebo , 1 to 5 capsules taken at bedtime ( qhs ) . Mianserin and amitriptyline were found to be comparable in efficacy , and both significantly more effective than placebo in the treatment of major depressive illness . Rating instruments , all of which showed significant improvement in the active drug groups over the placebo , included the 17- and 21-item Hamilton Rating Scale for Depression ( HAM-D ) , Montgomery and Asberg Depression Rating Scale ( MADRS ) , Self-rating Depression Scale ( SDS ) index , and the Clinical Global Impressions ( CGI ) Severity of Illness and Improvement rating scales . Furthermore , for most efficacy parameters in the efficacy-evaluable group , the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients . The safety profile for mianserin was comparable with placebo with respect to laboratory values , electrocardiogram changes , vital signs , ophthalmologic evaluations , and most adverse clinical experiences . Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups . Mianserin was superior to amitriptyline in terms of vital signs ; anticholinergic effects ; and complaints of dizziness , dyspepsia , and tremor MIA is an effective antidepressant , comparable in therapeutic efficacy to the TCAs . Further , because of its weak antimuscarinic effects . Further , because of its weak antimuscarinic effects , MIA produces no significant cognitive impairment , alteration of cardiovascular function of anticholinergic side effects compared to the TCA 's . While drowsiness is the most frequently reported adverse reaction with MIA , an h.s . dosing schedule can provide relief of insomnia and improve the quality of sleep ( 47,61 ) . Therefore , because of MIA 's advantageous pharmacodynamic profile , it offers an improvement in therapeutic index over the TCAs in the treatment of depression in the elderly SIR,-We wish to record a further instance of fatal paraquat poisoning . So far as we can ascertain , this is the tenth reported fatality caused by this widely used herbicidal preparation."q In December 1965 a 42-year-old male accidentally drank a small quantity of " weed-killer "  from an  unlabelled stout bottle . It was later estimated that the quantity of fluid consumed was about threequarters of a teaspoonful . The nature of the substance could not be immediately ascertained , but it was subsequently identified as Gramaxone 19 % ' w/w paraquat ion ) by the laboratories of I.C.I. Ltd. On admission to hospital a few hours after taking the poison , the patient complained of a  burning sensation in the throat and repeated -vomiting . Despite immediate gastric lavage , prophylactic penicillin , and abundant oral and intravenous fluids , there was progressive clinical deterioration . At three days the tongue was severely ulcerated and two days later haemoptysis occurred . On the eighth day jaundice , pyrexia , tachycardia , and a blood urea of 375 mg./100 ml . were recorded . The patient died some hours later . The outst and ing necropsy findings included focal myocardial necrosis , -severe pulmonnary haemorrhage and oedema , dense eosinophilic alveolar membrane , and proliferation of fibroblast-like cells in the alveolar septa . It is apparent from this and other reports that the lethal dose of paraquat may be very small . Further fatalities will -nly be avoided by proper , care in the storage and use of this valuable -but potentially dangerous compound . A detailed and illustrated clinico-pathological report is being prepared for publication.-We are , etc . Eighty-five female depressed patients were treated for 4 weeks with amitriptyline in a flexible dose ( median , 150 mg daily ) . Predictive analyses of outcome were carried out , using both typological and regressional models based on the same 29 predictor variables . The typological prediction utilized a previously described four-group typology derived by multivariate cluster analysis and comprising psychotic depressives , anxious depressives , hostile depressives , and young depressives with personality disorder . Patients were assigned to groups by discriminant functions on the basis of scores on the predictor variables . The four groups were found to predict outcome significantly . Psychotic depressives , initially the most severely depressed , improved the most ; anxious depressives , a little less severely ill initially , showed the least improvement and the most residual illness at 4 weeks ; hostile depressives and young depressives with personality disorders , initially the least severely ill , showed intermediate improvement and were least ill , by a small margin , at 4 weeks . The 29 predictor variables also predicted outcome significantly in linear multiple regression analyses . Five variables showed regression weights significantly different from zero : high initial severity predicted high improvement but more residual illness ; initial insomnia , more previous depressions , longer illness , and hypochondriasis all predicted low improvement and more residual illness . Predictions by using typological and regression models were compared , and their interrelationships were examined . The regression prediction accounted for more variance in outcome measures than did the typology , but the statistical significance s of the regression and typological predictions were of the same order . Two variables appeared particularly important — high initial severity of illness which characterized the psychotic depresives and increased number of previous depressions which characterized the anxious depressives . Typological prediction was not solely due to these two variables in linear regression model sicne it remained significant when the outcome measure was adjusted for both by analysis of covariance . Both typological and regressional models provide useful approaches to prediction , with only limited overlap . The typological approach , which has been relatively neglected in recent years , warents more frequent application as an alternative to multiple regression Summary Forty-five patients suffering from a major depression were administered zimeldine , amitriptyline or placebo ( 15 patients in each group ) in a double-blind controlled study . In the zimeldine group , seven of the 14 patients treated for more than one week presented a toxic syndrome consisting in a severe prostration , fever , myalgias and arthralgias . In all patients presenting this syndrome , laboratory analyses revealed an elevation of alkaline phosphatase and of aspartate and alanine aminotransferases and a decrease in white blood cell and platelet counts . Three patients presented a mild proteinuria and hematuria . Although an immunological mechanism can not be ruled out , several characteristics of this reaction suggest the formation of a metabolite of zimeldine with direct cellular toxicity . The relatively high starting dose of 200 mg/day of zimeldine administered in the present study and the increment to 300 mg/day after only seven days might have contributed to the high incidence of toxic reactions observed One hundred and fifteen patients from 5 general practice s participated in a 12-week , double-blind study comparing L-tryptophan , amitriptyline , L-tryptophan-amitriptyline combination and placebo in the treatment of depression . Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo . Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups . Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups , but this difference was not significant . Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups . St and ard haematological and biochemical profiles did not alter significantly in any group , but mean heart rate was significantly increased in patients receiving amitriptyline . There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms 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 In a multicenter , placebo-controlled , clinical trial , the efficacy of Limbitrol was compared with that of its components , amitriptyline and chlordiazepoxide .  All patients had a diagnosis of primary depression . Data from 279 patients were evaluated using the Hamilton depression scale , the Beck depression inventory , and physician and patient global change measures .Statistically significant differences favoring Limbitrol occurred after 1 week of treatment , and a trend in favor of Limbitrol continued throughout the remaining 3 weeks . In most efficacy comparisons , the combination was as good as , or better than , amitriptyline alone . It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment . Each component produced an independent contribution to the total therapeutic effect : the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks . A trend favoring amitriptyline over chlordiazepoxide was evident by week 4.The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups . Limbitrol-treated patients exhibited more sedation , but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects Of 580 patients r and omly assigned to short-term , double-blind treatment with either mirtazapine , amitriptyline or placebo , a total of 217 patients clinical ly judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study  ( mirtazapine , n = 74 ; amitriptyline , n = 86 and placebo , n = 57 ) . The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data . Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo ( p < 0.05 ) , and a significantly longer time to relapse was shown on the survival analysis . There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks , with fewer patients relapsing . There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis ( p < 0.05 ) . The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks . At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response , Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms , but there was no difference from placebo in the proportion of patients with sustained response .  Mirtazapine was well tolerated with a side-effect profile similar to that of placebo . The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain . Objective ly measured weight gain was more frequent with amitriptyline ( 22 % of patients ) compared with mirtazapine ( 13 % of patients ) . Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo , in particular sedative and anticholinergic side effects . The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression , which on some measures showed an advantage compared with amitriptyline , coupled with its improved side-effect profile , commends this antidepressant for the long-term treatment of depression ABSTRACT — Zimeldine tolerability was compared to amitriptyline and placebo in a large multicentre study performed at three clinical research units in the U.S.A. Prior to a placebo washout period of 3–7 days , patients were r and omly assigned to  zimeldine  , a potent and selective 5‐HT reuptake blocker , amitriptyline or placebo . Dosage range was 75–300 mg/day for active medications , and the scheduled treatment period was 4 weeks 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 relationship between treating physician 's prognosis and treatment response to active drug or placebo in sample s of 517 anxious and 569 depressed out patients who had participated in 4-week double-blind drug trials was examined . Log-linear analyses employing diagnosis , prognosis , treatment ( active drug or placebo ) , and treatment response were conducted . Anxious patients had been treated with either chlordiazepoxide or placebo , and depressed patients had received either amitriptyline or placebo . Significant differences were found , suggesting that physician prognosis is related to pharmacologically induced symptom relief in anxious but not in depressed patients . In the depressed patient sample , prognosis and improvement were found to be significantly related in placebo but not drug-treated patients Speed of onset of antidepressant effect was studied in 20 depressed out patients assigned double-blind to equipotent doses of amoxapine or amitriptyline . In counterbalanced order , each patient had 2 periods of 3 weeks on active agent interspersed with 2 similar periods of placebo control . On daily and weekly self-ratings , amoxapine was found to reduce symptoms significantly more rapidly than amitriptyline .  Psychiatrist-ratings were consonant with selfreports As reported by Prien ( see p 847 ) , two United States committees concluded in 1975 that lithium is prophylactically efficacious , ie , significantly better than placebo , in recurrent bipolar affective illness . The committees felt , however , that they could not recommend the prophylactic use of lithium in recurrent unipolar affective illness ( 1 ) because there is uncertainty as to what a unipolar disorder represents and ( 2 ) because the evidence for the efficacy of lithium in this disease type is based on a relatively small number of patients . With the first reason given , the committees more or less acknowledge that lack of trust in the psychiatrists ' ability to diagnose recurrent unipolar affective illness played a role in their decision . I have no comment to offer on this . As regards the second reason : It might be worth comparing the evidence now available for prophylactic efficacy of lithium and of cyclic antidepressants  in unipolar affective illness . 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 In a four-week study of 08 volunteer subjects with mixed symptoms of anxiety and depression , amitriptyline produced significantly more improvement than placebo . Significant differences were noted between the amitriptyline and placebo treatment groups at two weeks in relief of somatic and anxiety symptoms and at four weeks in relief of depressive symptoms . The marked sensitivity of the volunteers to certain amitriptyline-induced side effects appeared to be related to their relatively high level of education , employment , and anxiety . Comparison data indicated that the results obtained with volunteers are relevant to out patients treated in general practice 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 A step- search multiple regression procedure was applied to data obtained from 120 amitriptyline-treated and 138 placebo-treated depressed nonpsychotic out patients in order to : 1 ) assess the magnitude of the drug 's effect in an outpatient sample after the possibly contaminating effects of relevant sources of patient heterogeneity have been statistically removed and 2 ) identify predictors of response to amitriptyline , placebo , or both . Patient , illness , and treatment attributes deemed of possible relevance were employed as potential predictors . Patients were drawn from two city hospital clinics and the private practice s of both general practitioners and private psychiatrists . The double blind drug trial employed was of 4 weeks ' duration , and improvement was assessed through both a patient global rating of change and a pretreatment-post-treatment difference in physicianevaluated depressive psychopathology ( PDS improvement ) . The drug effect was highly significant . Its magnitude was left unchanged for global improvement and slightly enhanced for PDS improvement when possibly contaminating influences of other predictors were statistically controlled through the regression procedure . For both improvement measures , drug-placebo differences were greater in more severely than in less severely ill patients . For all patients , irrespective of treatment agent , acute illness 6 months ) responded better to treatment than did long term illness . For the global measure there were indications that the more adequate personal and social re sources , as well as the more favorable and realistic attitudes , of the higher socioeconomic class patient were instrumental in effecting greater  drug-placebo differences than occurred for patients of lower socioeconomic class affiliation . Finally , in replication of previous results , placebo patients were found to show greater global improvement when their physicians reported liking them less 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 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 The authors report clinical study of 34 asthmatic children between the ages of ten and 15 , followed at a specialized outpatient clinic of a large pediatric hospital in Montreal . Evaluation of the children and their families involved the use of clinical scores with inter-rater agreement . The study found strong associations between certain personality traits and an excessive use of medication , and between personality traits and family structure . Regardless of the severity of their asthma , children with high levels of anxiety and dependence were more likely to live with highly cohesive families and to use greater quantities of cortisone  than children with better adapted personality structures . Pathological family setting s are known to cause more emotional and behaviour problems in children . We suggest there is a reciprocal influence , and we consider the effects on the family of an early childhood disease that is persistent , worrisome , unpredictable , and necessitates repeated hospitalization . Prospect i ve studies of the high-risk subgroups identified in this study could facilitate early intervention for asthmatic children and their families 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 noradrenaline ( NA ) hypothesis of depression is founded primarily on pre clinical and clinical ly indirect evidence . In two three-compartment r and omized parallel clinical trials conducted serially , we examined the significance of NA uptake for antidepressant activity . The racemic compound oxaprotiline ( hydroxymaprotiline ) is a highly specific inhibitor of NA uptake , whereas its R-(- ) enantiomer levoprotiline is totally devoid of this property . Oxaprotiline significantly resembled amitriptyline in its antidepressant potential . Conversely , levoprotiline significantly resembled placebo in antidepressant potential . Therefore , NA uptake was necessary for the observed therapeutic effect of this experimental antidepressant Cognitive effects of brief antidepressant treatments were studied in depressed out patients assigned double-blind to equipotent doses of amoxapine or amitriptyline in a 12-week double-crossover of 3-week periods of active agent and placebo . The two drugs had different profiles of effects : amitriptyline was associated with faster reaction time on tests of attention and immediate memory , reduced accuracy on an attention task , and impaired long-term memory ( after 1 but not 3 weeks ) ; amoxapine slowed performance and increased intraperson variability on a psychomotor coordination task .  Amitriptyline facilitated performance in the more depressed patients , and amoxapine in the older patients . Both agents also increased pulse rate and reduced palmar sweating Abstract Objective : To determine whether , in the treatment of major depression in primary care , a brief psychological treatment ( problem solving ) was ( a ) as effective as antidepressant drugs and more effective than placebo ; ( b ) feasible in practice ; and ( c ) acceptable to patients . Design : R and omised controlled trial of problem solving treatment , amitriptyline plus st and ard clinical management , and drug placebo plus st and ard clinical management . Each treatment was delivered in six sessions over 12 weeks . Setting : Primary care in Oxfordshire . Subjects : 91 patients in primary care who had major depression . Main outcome measures : Observer and self reported measures of severity of depression , self reported measure of social outcome , and observer measure of psychological symptoms at six and 12 weeks ; self reported measure of patient satisfaction at 12 weeks . Numbers of patients recovered at six and 12 weeks . Results : At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant ( 5.3 ( 95 % confidence interval 1.6 to 9.0 ) and 4.7 ( 0.4 to 9.0 ) respectively ) , but the difference between problem solving and amitriptyline was not significant ( 1.8 ( −1.8 to 5.5 ) and 0.9 ( −3.3 to 5.2 ) respectively ) . At 12 weeks 60 % ( 18/30 ) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52 % ( 16/31 ) given amitriptyline and 27 % ( 8/30 ) given placebo . Patients were satisfied with problem solving treatment ; all patients who completed treatment ( 28/30 ) rated the treatment as helpful or very helpful . The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours . Conclusions : As a treatment for major depression in primary care , problem solving treatment is effective , feasible , and acceptable to patients . Key messages Key messages Patient compliance with antidepressant treatment is often poor , so there is a need for a psychological treatment This study found that problem solving is an effective psychological treatment for major depression in primary care — as effective as amitriptyline and more effective than placebo Problem solving is a feasible treatment in primary care , being effective when given over six sessions by a general practitioner Problem solving treatment is acceptable to This r and omized double-blind study in 342 mildly to moderately depressive out patients investigated the antidepressant effectiveness and speed of action of lorazepam , alprazolam and amitriptyline versus placebo . Six weeks of drug treatment were followed by a drug taper period , a control period with placebo and a control period without placebo , of 2 weeks duration each . Clinical improvement was assessed by rating scales ( Clinical Global Impressions , Hamilton Rating Scales for Depression and Anxiety ) and patient 's self-ratings ( Patient 's Global Impressions , Self-rating Depression Scale and Visual Analogue Scale ) . At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo . Compared to placebo , onset of efficacy was earlier on benzodiazepines than on amitriptyline . While tapering by decreasing the dosage , replacing drug with placebo and finally discontinuing placebo , clear withdrawal phenomena were not seen , but 20 % of patients , equally distributed to all treatment groups , did not want to stop taking tablets after replacing drug with placebo .  Drop-out rate during the treatment period was very low ( 9 % ) . Significantly interfering adverse effects were seen in 27 patients , without predominance in one of the active drug groups The National Institute of Mental Health ( NIMH ) Treatment of Depression Collaborative Research Program ( Elkin et al. , Archives of General Psychiatry , 46 , 971 - 982 ; 1989 ) reported treatment-by-severity interactions favouring pharmacotherapy for more depressed out patients , on a minority of relevant comparisons . The present study reports secondary analyses from a similar , preexisting data set in which treatment-by-severity interactions are systematic ally investigated with depressed out patients treated either with nondirective psychotherapy , behaviour therapy , pharmacotherapy , or relaxation/placebo . Despite multiple severity measures and variable severity cut scores , no treatment was differentially effective in improving more severely depressed patients . Also , there was little difference across symptom severity levels in the proportions of recovered patients between treatment groups . Finally , dynamic cluster analysis demonstrated that the proportion of pharmacotherapy nonresponders ( 20 % ) did not differ from the proportion of nonresponders in behaviour therapy or placebo groups . It is concluded that this failure to replicate the NIMH trial findings can not be attributed to treatment differences , population s or statistical power . The suggestion that pharmacotherapy be the treatment of choice for more severely depressed out patients appears to be unjustified on the basis of available evidence 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 We report on the results of a study comparing mianserin with amitriptyline and placebo , in out patients with major depression ( DSM-III 296.2 or 296.3 ) . One hundred and forty-nine patients were r and omized to mianserin ( n = 50 ) , amitriptyline  ( n = 50 ) or  placebo  ( n = 49 ) . Medication was taken in a nightly ( qhs ) dose . During Week 1 , the maximum dose was 60 mg mianserin , 120 mg amitriptyline or two placebo capsules . Beginning at Day 7 ( through Day 42 ) maximum dosages were 150 mg mianserin , 300 mg amitriptyline or five placebo capsules . At multiple weeks and endpoint , statistically significant reductions in the Hamilton Depression Scale ( HAM-D ) 17− and 21-item scores were recorded for both active drugs compared with placebo . Positive results with the HAM-D were corroborated by other measures of efficacy . There were no statistically significant differences between mianserin and amitriptyline in terms of efficacy ; however , the results do suggest a more rapid therapeutic response for mianserin compared with amitriptyline , in terms of percentage of patients showing ≥ 50 % improvement at Weeks 2 ( 30 % vs 23 % ) and 4 ( 61 % vs 44 % ) . The most common adverse experiences were somnolence  ( amitriptyline and mianserin 60 % , placebo 31 % ) and dry mouth  ( amitriptyline 76 % , mianserin 30 % and placebo 20 % ) . Our results indicate that mianserin is clearly superior to placebo , compares favorably with amitriptyline , and is a safe , well-tolerated , effective medication in the treatment of depressed out patients 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 Treatment efficacy is typically evaluated by examining group means and pre-post change scores . Although informative , such analyses may obscure individual or subgroup differences in response ( outcome profiles ) . The present study used two different methods to define treatment outcome profiles -- rationally-derived criteria ( Frank et al. , Archives of General Psychiatry 48 , 851 - 855 , 1991 ) and dynamic clustering -- to evaluate four treatments of unipolar depression : behaviour therapy , amitriptyline , psychodynamic psychotherapy and relaxation training ( attention placebo ) . The profiling methods yielded similar results . Regardless of treatment , the majority of patients displayed either a recovery or nonremission outcome profile , with relatively few instances of remission followed by a recurrence of depression . These findings challenge the view that any of the treatments are associated with a strong tendency to relapse , at least over the 3-month follow-up period . To further characterize the major outcome profiles , discriminant analysis was performed . Results indicated that recovery and nonremission profiles differed in that the latter was associated with a longer and more severe index episode and greater neuroticism . A number of variables , including family history of depression and therapists ' prediction of outcome , failed to distinguish recovered from unremitted patients BACKGROUND A r and omized controlled clinical trial compared three treatments for major depression in primary care . Ninety-one patients were r and omized to receive either problem-solving , or amitriptyline with st and ard clinical management , or drug placebo with st and ard clinical management . This paper examines the possible predictive value of a range of demographic clinical and personality variables in determining outcome . METHODS To examine the interaction between treatment group and predictor variables , analyses of co-variants were carried out for two outcome measures : the Hamilton Rating Scale for Depression and the Beck Depression Inventory . Predictor variables were also entered into a stepwise forward logistic regression in which patients were categorized as recovered or not recovered . RESULTS None of the predictor variables examined interacted with treatment to predict outcome . Patients with a longer duration of illness , chronic social difficulties , or definite , as opposed to probable , major depression had a poorer outcome at the end of treatment , irrespective of treatment group . CONCLUSIONS The findings in this study do not enable clear guidelines to be given as to which patients with major depression in primary care might benefit from either a psychological or pharmacological treatment Demographic and auxological data were analysed from 818 girls with Turner 's syndrome treated with recombinant human growth hormone ( GH ) and entered into the Kabi Pharmacia International Growth Study . Size at birth was low and correlated with the heights of both parents . The median age at start of GH  treatment was 11.4 years and the parents had a median height SDS of ‐2.9 . Height SDS at the start of treatment correlated with parental heights . Height velocities conformed to Turner‐specific st and ards . The weight‐for‐height index increased sharply above 9 years of age . The frequency of spontaneous appearance of Tanner breast stage 2 was high ( 34.1 % of girls > 10 years of age ) . Bone age ( Greulich and Pyle ) data were described by the equation : bone age = 1.61 ( chronological age ) ‐0.04(chronological age)2 ‐ 3.61 . This equation was used to correct adult height predictions . The median initial dose of GH  was 0.8 IUkglweek and was maintained during the first 3 years of treatment . The median frequency of injections was six/week . Height velocity increased from 4.1 to 6.8 cm/year in the first year , and height velocity SDS for chronological age remained positive for 4 years . The height prediction corrected for bone age increased over the first 2 years only . Differences in demography and auxology were described according to karyotype and country of origin . A greater height velocity SDS was observed at higher GH doses and when ox and rolone was used concomitantly 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 Weight data taken from a 6-week r and omized double-blind study comparing amitriptyline , trazodone and placebo were analyzed to determine differential weight changes between the two drugs . In 272 depressed out patients doses were increased over a period of 4 days to reach a maximum level of 200 mg amitriptyline or 400 mg trazodone . After grouping the subjects according to initial weights ( ideal , overweight , 20 % above , and underweight , 20 % below ) mean changes were determined for each treatment . The results indicate that amitriptyline , which differed from placebo and trazodone , produced significantly higher weight gains in the ideal and overweight groups . Trazodone on the other h and produced a slight weight loss in the overweight group . Due to a low number of patients in the underweight group , the results were not significantly statistically . The antidepressant effects of both trazodone and amitriptyline were the same and no correlations between Hamilton scores and weight change were found 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 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 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 The authors contrasted four treatments for unipolar ( nonpsychotic ) depression : 1 ) amitriptyline , 2 ) social skills training plus amitriptyline , 3 ) social skills training plus placebo , and 4 ) psychotherapy plus placebo . They studied 72 female out patients , 52 of whom completed the 12 weeks of treatment . The four treatments , conducted by experienced clinicians , were not substantially different from one another . Each treatment produced significant and clinical ly meaningful changes in symptomatology and social functioning . However , the authors identified several notable differences across groups : a significant difference in dropout rates ( from a high of 55.6 % for the amitriptyline group to a low of 15 % for the social skills plus placebo group ) and a significant difference in the proportion of patients who were substantially improved . The social skills plus placebo treatment was the most effective treatment on this dimension A study of 203 depressed out patients who were r and omly assigned to one of seven active drug treatment groups or to a placebo group demonstrated that the inclusion of a placebo group is essential for valid assessment of the efficacy of antidepressant drugs . Although all groups improved on depression ratings in relation to their own baselines , only one group achieved a level of improvement that was significantly better than that of the placebo group Abstract 3-Cyano-imipramine ( cianopramine ) is a potent and selective inhibitor of serotonin uptake into synaptosomes . In a double-blind trial , 60 patients with various types of depression fulfilling the DSM-III criteria of depressive episodes were treated with either cianopramine ( n=20 , mean daily dose 3.3±0.6 mg ) amitriptyline ( n=20 , mean daily dose 86.4±21 mg ) or placebo ( n=20 ) orally . According to the ratings of the Hamilton Scale of Dpression and clinical global evaluations , both active drugs showed statistical superiority over placebo ( P<0.02 ) . The frequencies of anticholinergic side effects in the cianopramine group were comparable to those of the placebo group and were less than in the amitriptyline group . The findings suggest that cianopramine is a promising new antidepressant Electrocardiograms of 65 patients treated with dothiepin , a sulphur substituted tricyclic antidepressant , were compared to those of 57 patients receiving amitriptyline and 62 patients given placebo . Amitriptyline produced an average heart rate increase of 10 beats/minute as compared to 5 beats/minute for dothiepin ( p less than .02 ) . Amitriptyline also produced a significant prolongation of the corrected QT interval as compared to both dothiepin and placebo ( p less than .01 and p less than .001 , respectively ) . Dothiepin had no significant effect on any index of myocardial conduction ( PR interval , corrected QT interval , and QRS duration ) as compared to placebo Fifty out- patients took part in a double-blind controlled comparison of two antidepressants dothiepin and amitriptyline . The subjects ' psychiatric state was assessed by both self-rating and clinician-rated scales . Patients were followed up for a period of about three months . The results of the trial showed that dothiepin was superior to amitriptyline at the 5 % significance level in terms of its antidepressant activity .  Dothiepin was better tolerated in relation to its side effects than amitriptyline . For relief of anxiety symptoms both drugs appeared equally effective 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 The purpose of this study was to compare the effects of amitriptyline and ECT in the treatment of depression . Thirty patients were assigned r and omly to 4 treatment groups : amitriptyline , ECT , placebo and simulated ECT .  Global improvement ratings , the Depression Rating Scale , the Ward Observation Inventory , the M.M.P.I. , the Wechsler-Bellevue Intelligence Scale and the Bender-Gestalt test were used in evaluating the response to treatment . Amitriptyline and ECT were both more effective than control procedures . There was no appreciable difference after one month of treatment between the therapeutic effects of amitriptyline and ECT 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 Discriminant function analyses were applied to data obtained from anxious psychiatric out patients treated with either chlordiazepoxide ( n = 353 ) or placebo ( n = 259 ) and depressed out patients treated with either amitriptyline ( n = 310 ) or placebo ( n = 328 ) , who had participated in controlled drug trials of 4 weeks ’ duration , in an attempt to identify factors associated with complaints of drowsiness made by these patients . Although the magnitude of the relationships between individual predictors and drowsiness was small , several factors emerged which had consistent impact across treatment groups . Predictors of complaints of drowsiness attributed to active drugs arose primarily from demographic attributes probably reflective of life style , and from illness and treatment history . In contrast , predictors of drowsiness attributed to placebo were almost exclusively confined to indices of the severity of several aspects of presenting symptomatology . In particular , more frequent complaints of drug‐induced drowsiness were found among better educated individuals with an illness of long duration . Complaints of placebeinduced drowsiness were more common among patients with more severe emotional ( phobic‐obsessive ) symptomatology and more frequent headaches and among those individuals in whom hypochondriasis was less severe Out patients with depression and mixed anxiety-depression were treated for six weeks with phenelzine sulfate , amitriptyline hydrochloride , or placebo in a controlled trial . Both active drugs were superior to placebo and were closely comparable in efficacy . Interactions were examined between drug response and classifications based on three different usages of the term atypical depression : additional anxiety or phobic symptoms , atypical functional shift , and nonendogenous depression . Some additional related classifications were also included . There was a tendency for phenelzine to have stronger effects in patients with additional anxiety and without evidence of chronic characterological depression . However , interactions were relatively few . These findings suggest that the two classes of antidepressant affect similar clinical subgroups within the outpatient depressive spectrum , with only relatively weak differences Data regarding open-label treatment with fluoxetine following failure to respond to tricyclic antidepressants ( TCAs ) or intolerance of TCA side effects , suggest a response rate between 51.4 % and 62.1 % , depending on the definition of TCA refractoriness employed . Double-blind study of this issue would extend these findings . Fluoxetine is well tolerated in patients unable to tolerate TCAs .  Within this population , more than 80 % of patients unable to tolerate TCAs found fluoxetine acceptable . Fluoxetine , as an alternative to polypharmaceutical augmentation , may represent a logical choice as the next step in therapy for a patient who has initially been treated with a TCA and has proven refractory or intolerant 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 Thirty-nine unipolar depressed patients were treated , after a washout period of seven days in a double blind study with either moclobemide , placebo or amitriptyline , for 42 days . The psychopathological assessment and HRSD were done on seven day intervals and thyroid analysis was done on 14 day intervals . At the end of therapy , the levels of T4 and fT4 decreased significantly in the responders if amitriptyline was used , and non-significantly if placebo or moclobemide were used . The T4 and fT4 values of the non-responders increased non-significantly . The weight change was minimal and non-significant & NA ; Changes in appetite and weight were examined in a group of 47 carefully diagnosed primary depressives who were treated in a r and om design with either placebo ( N = 17 ) or amitryptyline ( N = 30 ) over a 35‐day protocol . While the amitriptyline treated group as a whole showed a greater gain in weight than did the placebo group ( 4.5 vs. 0.5 lb , p < 0.05 ) , no differential effects could be demonstrated between drug responders and nonresponders . Likewise , while a consistent relationship between the self‐report of decreased appetite and final weight change was noted in the placebo group , no simple relationship between final weight change and self‐reported changes in appetite were apparent in the drug‐treated patients . There was , however , a relationship between the report of decreased appetite and clinical severity of depression in the drug nonresponder subgroup despite significant weight gain during the protocol . Thus , weight change during this study period did not appear to show a simple relationship to corresponding clinical change . The clinical lore that has supported the notion that increased appetite and weight gain in patients being treated with tricyclic antidepressants are “ good ” signs can not be confirmed by our findings Eighty-six depressed in patients were divided into four groups : patients in each of three groups were treated , respectively , with identical capsules of verapamil , amitriptyline , or placebo , whereas the fourth group was treated eclectically by the ward physician with so-called state-adjusted treatment ( SAT ) . Each treatment period lasted 5 weeks . Psychopathology was assessed with the Hamilton Rating Scale for Depression , by the Zung self-rating scale , by the 100-mm analog scale , and by general clinical impression . Results indicated that amitriptyline and SAT were superior to verapamil or placebo . There was no significant difference between verapamil and placebo or between SAT and amitriptyline . This finding was more definitive in the homogeneous subgroup of 55 women with DSM-III diagnosis of Major depression . In addition , 12 manic in patients ( DSM-III ) were treated orally with verapamil , 24 with neuroleptics , and 11 with both neuroleptics and lithium carbonate . The decline of their psychopathology , assessed by the Brief Psychiatric Rating Scale ( BPRS ) and general impression , was fully comparable . Using Analysis of Variance ( ANOVA ) , the statistical difference among courses of psychopathology expressed as total BPRS scores reaches borderline significance in favor of verapamil . In contrast to neuroleptics , verapamil did not induce any sedative , hypnotic , or cataleptic effects , and was well tolerated Comparative effects of the antidepressant drug , amitriptyline hydrochloride , marital therapy , and the drug-psychotherapy interaction effects were studied in a 12-week course of treatment of outpatient depressives . Patients were assigned r and omly to four treatment groups , in a 2 times 2 factorial design : ( 1 ) drug-marital therapy ; ( 2 ) drug-minimal contact ; ( 3 ) placebo-marital therapy ; and ( 4 ) placebo-minimal contact . Both drug and marital therapy showed substantial beneficial advantages over their control conditions , but drug therapy was faster and generally superior in symptom relief and clinical improvement . Marital therapy was superior in family role task performance and perception of the marital relationship . For reducing hostility and enhancing the perception of the marital relationship , drug therapy had a better early effect , but marital therapy had superior effects by the end of treatment 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 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 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 Summary The study compares the therapeutic effects of a sustained release form of amitriptyline ( ‘ Lentizol ’ ) with st and ard amitriptyline in depressed patients using a higher dosage than previously reported . Clinical results were correlated on the Hamilton scale and the Wakefield self- assessment inventory . Similar therapeutic effect was found from the sustained release formulation at two-thirds the dosage of the st and ard amitriptyline .  Side-effects were not significantly different in the two groups ; except the sustained release version produced less dryness of the mouth but increased incidence of mild difficulties in micturition To investigate the effectiveness of a new benzodiazepine , alprazolam , and to compare this with amitriptyline ( AMT ) and with placebo , a trial was undertaken in 65 patients in whom depression was considered to be the dominating feature but not considered to be the primary cause of their condition ; it was design ed to exclude endogenous depressions . A consistent pattern was found favouring alprazolam over AMT both in rate of response and in total response , as well as significant differences in favour of both alprazolam and AMT over placebo . A comparison of side effects showed a definite trend in favour of alprazolam and placebo over AMT 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 The authors reanalyzed data from two earlier studies that used double-blind placebo-controlled formats to study the efficacy of amitriptyline . Using a 14-day drug-free ' wash-out ' period , they found that the  placebo response rates were 0 % for psychotic depressives and 13.3 % for nonpsychotic depressives .  Amitriptyline  was significantly superior to placebo for both psychotic ( P less than or equal to 0.05 ) and nonpsychotic ( P less than or equal to 0.05 ) depressed patients The perceived intensity of a stimulus may be magnified during depression . Stimulus intensity control can be studied by means of cortical evoked potentials . In a study of 33 depressives , cortical evoked potentials were greater during depression than on recovery . The effect of doxepin on the amplitudes of evoked potentials of depressives was compared with that of amitriptyline . Doxepin reduced amplitudes .  Amitriptyline had a similar , but non-significant effect In a 7-week prospect i ve multicentre study , the efficacy , tolerability and safety of moclobemide were compared to those of amitriptyline and placebo in parallel groups of out- patients ( n=173 ) fulfilling the DSM III-R criteria for a major depressive episode . Participants were required to have a minimum baseline total score of 18 on the 17-item Hamilton Depression Rating Scale ( HAMD ) . After a 1-week placebo washout , patients were r and omly allocated to the three treatment groups . Assessment of efficacy , as judged by the number of responders achieving a 50 % reduction in HAMD score by the end of treatment , showed that both moclobemide and amitriptyline were significantly superior to placebo , but that they were not significantly different from each other . Both treatments differed significantly from placebo with respect to the Physician 's Global Assessment of Efficacy ( ‘ very good ’ or ‘ good ’ response : moclobemide 57 % , amitriptyline 60 % and placebo 35 % ) . Assessment of tolerance as judged by the spontaneous reporting of adverse events showed a significant superiority of moclobemide over amitriptyline , but there was no significant difference between moclobemide and placebo . At termination of the study , amitriptyline patients showed a significant elevation of heart rate both supine ( 10.8 beats/min ) and st and ing ( 15.5 beats/min ) , as well as significant weight gain ( 1.7 kg ) , but no changes were seen in the moclobemide or placebo groups . In conclusion , both moclobemide and amitriptyline were found to be more effective than placebo in the treatment of depression , while moclobemide had fewer side effects
target: 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: 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 .