A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder. A controlled study of mianserin in moderately to severely depressed outpatients. A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicentre study. Controlled trial of zimelidine, a 5-HT reuptake inhibitor, for treatment of depression. Verapamil in affective disorders: a controlled, double-blind study. Comparative effects of phenelzine and amitriptyline: a placebo controlled trial. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Trazodone in depressed outpatients. Thyroid functioning during treatment for depression. A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression. Cianopramine and amitriptyline in the treatment of depressed patients--a placebo-controlled study. Clovoxamine in the treatment of depressed outpatients: a double-blind, parallel-group comparison against amitriptyline and placebo. Controlled trial of amitriptyline in general practice. A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients. A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness. Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care. The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo. A double-blind non-crossover placebo-controlled study between group comparison of trazodone and amitriptyline on cardiovascular function in major depressive disorder. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Relationship between response to phenelzine and MAO inhibition in a clinical trial of phenelzine, amitriptyline and placebo. Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients. A double-blind evaluation of zimelidine in comparison to placebo and amitriptyline in patients with major depressive disorder. A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. Neuropsychological assessment and EEG sleep in affective disorders. A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression. Antidepressant response and plasma concentrations of bupropion. Amoxapine and amitriptyline. I. Relative speed of antidepressant action. Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression. Changes in weight during treatment for depression. High incidence of multisystemic reactions to zimeldine. Platelet alpha-2 adrenoreceptor activity pre-treatment and post-treatment in major depressive disorder with melancholia.
In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients. Following a 1-week, single-blind placebo washout, 150 patients were randomized 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. In a 7-week prospective 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 randomly 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 standing (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. 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. Eighty-six depressed inpatients 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 inpatients (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. nan Five hundred four outpatients suffering from a major depressive episode were randomly 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. The authors compared the nontricyclic antidepressant trazodone with amitriptyline and placebo in a double-blind study of 202 unipolar depressed outpatients. Trazodone's clinical efficacy was similar to that of amitriptyline, with both active drugs producing significantly more clinical improvement than placebo. The incidence of anticholinergic side effects was lower for the patients taking trazodone than for those taking amitriptyline. 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. A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo.
                One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo.
                At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo.
                In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety. 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 Depression and clinical global evaluations, both active drugs showed statistical superiority over placebo (P less than 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. In a double-blind, random-assignment, parallel-group trial, outpatients 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. 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. This study was designed 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.
                Outpatients with DSM-III-R major depression were randomly assigned to double-blind treatment for 8 weeks with sertraline (50-200 mg daily), amitriptyline (50-150 mg daily), or matching placebo. Assessments 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 Questionnaire, and Health-Related Quality of Life battery.
                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.
                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. We report on the results of a study comparing mianserin with amitriptyline and placebo, in outpatients with major depression (DSM-III 296.2 or 296.3). One hundred and forty-nine patients were randomized 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 > or = 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 outpatients. 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. 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.
                Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks.
                Primary care in Oxfordshire.
                91 patients in primary care who had major depression.
                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.
                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.
                As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients. One hundred and fifteen patients from 5 general practices 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. Standard 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. 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. Patients (n = 150) were randomized 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. 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. 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 random. 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. This paper presents the results from a large multicenter study, performed at three clinical research units in the USA. Prior to a three to seven days of placebo washout period, patients were randomly assigned to zimelidine, a potent and selective 5-HT reuptake blocker, amitriptyline or placebo. The scheduled treatment period was four weeks. Dosage range was 75-300 mg/day for active medications. The rating instruments were the Hamilton Depression Scale and the Clinical Global Impression scale. The side effects were recorded by using a side effect inventory (TESS). Vital signs, laboratory work including clinical chemistry, ECG, and plasma levels of drugs, were performed. In the main efficacy evaluation there were 229 depressed outpatients included, all having completed at least two weeks of treatment after the washout period. The patients treated with zimelidine as well as those treated with amitriptyline showed a significant improvement relative to the placebo treated patients. For the safety evaluation 263 patients were included. Side effects, in particular anticholinergic effects but also drowsiness and cardiovascular effects, were much less pronounced in the zimelidine group as compared to the amitriptyline group. Only marginal differences regarding side effects were reported for zimelidine compared to those reported for placebo. The noradrenaline (NA) hypothesis of depression is founded primarily on preclinical and clinically indirect evidence. In two three-compartment randomized 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. 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 randomly 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. The neuropsychological test performance of 76 hospitalized, depressed patients meeting RDC for the presence of affective disorder was assessed as part of a protocol involving amitryptyline (n = 53) or placebo (n = 23). Tests included the Trail-making Test (TMT), the Benton Visual Retention Test, and the Shipley-Hartford Scale. Clinical ratings and data concerning the characteristics of EEG sleep were also obtained. Analysis of data collected after a drug-free period of 2 weeks and again at the end of the protocol yielded the following conclusions. Base-line performance was inferior to norms for these tests, but for the TMT, scores were not as poor as that expected for brain-damaged patients. Poor performance was often associated with older age, the presence of psychotic features, and prolonged sleep latencies. Baseline Hamilton Rating Scale (HRS) was predicted best by TMT part B. However, this association was not as strong as that between HRS and poor sleep efficiency. Treatment with drug or placebo had little differential effect upon test performance over the course of the protocol. It is suggested that further research should utilize tests which have specificity in localizing cerebral lesions, so that any focal deficits in brain function in depression might be identified. We performed a randomized, double-blind clinical trial comparing the efficacy and safety of zimelidine with amitriptyline and placebo in outpatients 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. 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 samples 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. Speed of onset of antidepressant effect was studied in 20 depressed outpatients assigned double-blind to equipotent doses of amoxapine or amitriptyline. In counter-balanced 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 self-reports. 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. 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. Changes in appetite and weight were examined in a group of 47 carefully diagnosed primary depressives who were treated in a random 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 less than 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 cannot be confirmed by our findings. 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 cannot 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. 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.
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.