Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group.

An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.

Efficacy and tolerability of moclobemide in comparison with placebo, tricyclic antidepressants, and selective serotonin reuptake inhibitors in elderly depressed patients: a clinical overview.

OBJECTIVE: To review the efficacy and safety of moclobemide in comparison with TCAs (for our purposes, "TCAs" will represent tricyclic and tetracyclic antidepressants, including maprotilin and mianserin) and selective serotonin reuptake inhibitors (SSRIs) in elderly depressed patients. METHODS: The efficacy data reviewed were obtained from the following sources: 1) results of published studies in the elderly; 2) data on patients aged > or = 60 years extracted from all available controlled trials in adults (> or = 18 years) in which moclobemide was compared with TCAs or SSRIs; and 3) the adverse events were extracted for patients aged > or = 60 years from the safety data base of all available comparative short-term studies with moclobemide versus TCAs, SSRIs, or placebo and of long-term studies with moclobemide. RESULTS: The data show that moclobemide is an effective antidepressant in depressed patients aged > or = 60 years. The response rate to moclobemide was 50% to 55% in this population. Moclobemide was more effective than placebo and was of similar efficacy to the TCAs and the more recently introduced SSRIs. The tolerability of moclobemide was rated as "very good" or "good" in almost 90% of these patients, which was better than the tolerability of TCAs and similar to that of SSRIs. Patients without any adverse events were more frequently found in the moclobemide group than in those treated with TCAs (P < 0.01) or SSRIs (P < 0.01). Adverse events of the anticholinergic type were more frequent with TCAs than with moclobemide (P < 0.001), and nausea was found 3 times more frequently with SSRIs than with moclobemide (P < 0.01). CONCLUSIONS: Moclobemide is an effective and well-tolerated antidepressant for the treatment of elderly depressed patients.

Modification of the cardiovascular effects of ephedrine by the reversible monoamine oxidase A-inhibitor moclobemide.

Irreversible, nonselective monoamine oxidase (MAO) inhibitors have been reported adversely to interact with indirectly acting sympathomimetic amines present in many cough and cold medicines. This study investigated the safety and tolerability of concomitant administration to 12 healthy subjects of both genders (aged 19-36 years) of ephedrine and moclobemide, a reversible MAO-A inhibitor. A 2-day, randomized, crossover administration of placebo or ephedrine (two doses of 50 mg with a 4-h interval) was followed by 9 days open-label dosing with moclobemide, 300 mg b.i.d.. On the last 2 days of moclobemide dosing, the randomized crossover treatment of ephedrine and placebo was repeated. No subject was withdrawn from the study for tolerability reasons. Moclobemide treatment, however, increased the incidence of adverse events elicited by ephedrine, particularly palpitations and headache. The pharmacodynamic interaction between the two drugs was quantified by calculation of the area under the effect-time course (AUE) for systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR). The difference in AUE between monotreatment with ephedrine and placebo was statistically significant for all three vital signs. Moclobemide potentiated the effect of ephedrine by a median factor of 3.2 for SBP, 3.8 for DBP, and 0.6 for HR. Ephedrine had no significant influence on the plasma concentrations of moclobemide or its metabolites. In conclusion, the combined use of moclobemide and high doses of sympathomimetic drugs should be approached with caution.

Moclobemide: a paradigm of research in clinical psychopharmacology.

The pre-clinical development of moclobemide is an example of broad research combined with serendipity. Moclobemide was first hypothesized as being an antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and moclobemide was then suspected of being an antipsychotic before its specific and reversible monoamine oxidase (MAO)-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977. In the first stage, multiple, small open and double-blind studies were carried out. Two decisive, large, multicentre, double-blind studies were later performed in Latin America and Austria. Further trials have confirmed the broad antidepressant activity of reversible monoamine oxidase inhibitors (RIMA), which is not confined to any one subtype of depression and which show good tolerability and low toxicity. Since moclobemide has been available on the market, extensive meta-analyses of a large data set provided a series of methodological results: factor structure of the Hamilton Depression Scale (HAMD), optimal criteria of efficacy, predictors of response, onset of action for antidepressants and placebo.

Plasma levels of the enantiomers of thioridazine, thioridazine 2-sulfoxide, thioridazine 2-sulfone, and thioridazine 5-sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin.

Concentrations of total (R) + (S) and of the enantiomers (R) and (S) of thioridazine and metabolites were measured in 21 patients who were receiving 100 mg thioridazine for 14 days and who were comedicated with moclobemide (450 mg/day). Two patients were poor metabolizers of dextromethorphan and one was a poor metabolizer of mephenytoin. Cytochrome P450IID6 (CYP2D6) is involved in the formation of thioridazine 2-sulfoxide (2-SO) from thioridazine and also probably partially in the formation of thioridazine 5-sulfoxide (5-SO), but not in the formation of thioridazine 2-sulfone (2-SO2) from thioridazine 2-SO. Significant correlations between the mephenytoin enantiomeric ratio and concentrations of thioridazine and metabolites suggest that cytochrome P450IIC19 could contribute to the biotransformation of thioridazine into yet-unknown metabolites, other than thioridazine 2-SO, thioridazine 2-SO2, or thioridazine 5-SO. An enantioselectivity and a large interindividual variability in the metabolism of thioridazine have been shown: measured (R)/(S) ratios of thioridazine, thioridazine 2-SO fast eluting (FE), thioridazine 2-SO slow eluting (SE), thioridazine 2-SO (FE+SE), thioridazine 2-SO2, thioridazine 5-SO(FE), and thioridazine 5-SO(SE) were (mean +/- SD) 3.48 +/- 0 .93 (range, 2.30 to 5.80), 0.45 +/- 0.22 (range, 0.21 to 1.20), 2.27 +/- 8.1 (range, 6.1 to 40.1), 4.64 +/- 0.68 (range, 2.85 to 5.70), 3.26 +/- 0.58 (range, 2.30 to 4.30), 0.049 +/- 0.019 (range, (0.021 to 0.087), and 67.2 +/- 66.2 (range, 16.8 to 248), respectively. CYP2D6 is apparently involved in the formation of (S)-thioridazine 2-SO(FE), (R)-thioridazine 2-SO(SE), and also probably (S)-thioridazine 5-SO(FE) and (R)-thioridazine 5-SO(SE).

Moclobemide versus clomipramine in nonmelancholic, nonpsychotic major depression. A Study group.

The efficacy and the safety of moclobemide (400-600 mg/day), a reversible and selective inhibitor of monoamine oxidase-A (RIMA) and of clomipramine (100-150 mg/day) were compared respectively in 98 and 93 nonmelancholic, nonpsychotic out-patients with a DSM-III major depressive episode over 6 weeks and up to 3 months, in a multi-center double-blind trial. No statistically significant difference between the treatments was found on the number of responders, at 6 weeks and 3 months, to the Hamilton Depression Rating Scale (HDRS), which was the main criterion for efficacy. The sample size was sufficient to detect a difference of approximatively 20% in response rates. Reduction of the total scores on HDRS and Covi anxiety scale was comparable for both treatments, but the reduction on the Retardation Depressive Scale (RDS) was significantly higher with moclobemide at the 1- and 2-week assessments. According to the RDS as well as the global impression of both patient and physician, a somewhat earlier onset of antidepressant action was evident in the moclobemide group. Tolerance was significantly better in the moclobemide group, mainly due to a lower frequency of weight gain, sedation and anticholinergic effects.

Moclobemide and tricyclic antidepressants in severe depression: meta-analysis and prospective studies.

There is no generally accepted definition of severe depression, but hospitalization, high scores on rating scales, and the presence of psychotic symptoms are widely considered to be indicators of severe cases. For the purpose of this analysis of the antidepressant efficacy of the reversible inhibitor of monoamine oxidase A moclobemide, all hospitalized cases were selected from the current database of comparative studies and compared with the standard tricyclics imipramine and clomipramine. The cases from comparisons of moclobemide and imipramine were analyzed together, because in accordance with the recommended range of doses, the dose ratio over all studies was approximately 3:1 (moclobemide: N = 238, mean dose, 453 mg/day; imipramine: N = 248, mean dose, 159 mg/day). The cases from comparisons of moclobemide and clomipramine could only be analyzed over all studies if dose was taken into account, because the dose ratio of approximately 3:1 was only given in one study (moclobemide: N = 62, mean dose, 466 mg/day; clomipramine: N = 66, mean dose, 154 mg/day), whereas the dose ratio over the other, earlier studies was approximately 2:1 (moclobemide: N = 58, mean dose, 258 mg/day; clomipramine, N = 59, mean dose, 124 mg/day). The efficacy as judged on the Hamilton Rating Scale for Depression (HAM-D) and Global Assessment of Efficacy was analyzed for subgroups of inpatients, according to different severity bands (17-item HAM-D baseline total score, cut-off, 28 points) and according to the presence or absence of mood-congruent psychotic features. The results of our analysis failed to reveal any difference in efficacy between moclobemide and imipramine in any subgroup of hospitalized depressives, including patients in the highest HAM-D severity band and psychotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind comparison of moclobemide and thioridazine versus moclobemide and placebo in the treatment of refractory, severe depression.

In a multicenter study of 78 severely depressed inpatients (44 women and 34 men; age range, 23 to 70 years), the efficacy, onset of efficacy, and tolerability of the reversible monoamine oxidase-A inhibitor moclobemide (450 mg/day) in combination with thioridazine (100 mg/day) were compared with those of moclobemide (450 mg/day) plus placebo. Patients enrolled met the DSM-III-R criteria for severe depression and had a severity score of at least 20 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Additionally, these patients had not responded to at least two standard antidepressants during the 2 years preceding screening and the mean duration of the current episode was 6 months. After a washout period of 3 to 5 days, patients were randomized to one of the two treatment groups, which at the outset had similar characteristics. Efficacy was assessed by the HAM-D, a depression observation rating for nurses, and a Clinical Global Impression (CGI) scale. Tolerability assessments included an overall rating, a description of adverse events, vital signs, electrocardiogram, and laboratory tests. After 4 weeks of therapy, both groups of patients showed significant improvements in HAM-D and CGI scores. The response rates (based on HAM-D > or = 50% decrease) were 74% for moclobemide/thioridazine and 77% for moclobemide/placebo, and according to CGI scores, 76 and 72% were "very much improved" or "much improved," respectively. Onset of effect was noted after 9.2 and 9.8 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of concurrent diazepam treatment on the outcome of exposure therapy in agoraphobia.

In a study designed to evaluate the impact of benzodiazepine use on the outcome of behaviour therapy, 91, severe, chronic agoraphobics (46 BDZ users and 45 non-users) were randomly allocated on a double-blind basis to in vivo exposure with low-dose diazepam (ED) or placebo (EP). Drug doses were adjusted on the basis of weekly psychiatric assessments over weeks 1-4. Patients had 8 x 2 hr exposure sessions (weeks 5-12) and were then withdrawn from medication (weeks 13-16). Re-assessments were completed at weeks 4, 12 and 16, and follow-up assessments at approx 20, 46 and 72 weeks. In the analysis of the results, the clinical outcome was evaluated in relation to the therapeutic regime (ED vs EP) and prior BDZ use (users vs non-users). The results showed that the ED group had greater changes in anxiety than the EP group during the drug manipulation phases (anxiety increasing during BDZ withdrawal). There were no group differences in agoraphobic symptoms and no evidence that the outcome of the behavior therapy was significantly affected by concurrent BDZ treatment. There were significant improvements in agoraphobic symptoms over the treatment period, with no evidence for relapse of treatment gains on withdrawal from BDZ, nor for differential responses over the one year follow-up. Initial differences between users and non-users were less marked than expected, although there was a trend for more drop-outs among users across both ED and EP groups.

Safety and efficacy during long-term treatment with moclobemide.

Safety aspects [adverse events, blood pressure and heart rate, weight, and laboratory tests (liver parameters, hemoglobin, leukocytes)] of long-term treatment in 1,120 patients are discussed. Adverse events during this long-term treatment were also compared with those of a subgroup of these patients who, before long-term treatment, were treated on a short-term basis (n = 706). Efficacy [Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression of Efficacy (CGI), and occurrence of relapses and recurrences] in a homogeneous sample of 485 patients is also discussed. The adverse events most frequently observed during long-term treatment were insomnia, headache, and dizziness. Insomnia and headache were also most often occurring in the compared sample of patients with short-term treatment, whereas dizziness during this treatment period ranked at the fifth position. Supine and standing mean blood pressure did not consistently change during long-term treatment, the most prominent increases in comparison with baseline were seen in the period > 1 year of treatment (6.3 mm Hg supine/7.2 mm Hg standing). Comparison of blood pressure values in the hypertensive range at baseline and during long-term treatment revealed no statistical difference (McNemar test p = 0.07829). Mean heart rate slightly decreased during long-term treatment (by a maximum of 6.3 beats/min supine, 8.2 beats/min standing). Mean weight did not change between baseline and treatment end point. There were 23 patients with a weight loss of 10 kg or more and 16 patients with a weight gain of 10 kg or more. For none of the laboratory parameters tested was there a statistical significance regarding shifts from normal to pathological values. HAM-D mean total scores in the above-mentioned subgroup of patients decreased from 25.05 points at baseline (n = 485) to 7.88 points after 1 year of treatment (n = 139). Seventy-five patients who had favorably responded to treatment (total responders n = 300) relapsed during the first 6 months of treatment. During the second half-year of treatment the recurrence rate was 14.8%, and during the third 6 months the recurrence rate was 12.2%. CGI in the same subsample of patients in whom HAMD was evaluated (n = 485) compared with those patients who did not drop out during the short-term period up to 44 days and entered long-term treatment (n = 401) showed that the percentage of the ratings "no change/worse" was higher in the sample that also included patients who withdrew from treatment during the short-term period.(ABSTRACT TRUNCATED AT 400 WORDS)

Double-blind comparison of moclobemide and tranylcypromine in depression.

Moclobemide is the first of a new generation of reversible inhibitors of monoamine oxidase-A (RIMA) with no clinically relevant potentiation of the hypertensive actions of dietary tyramine. The present study was conducted to compare the efficacy and safety of moclobemide with an established irreversible monoamine oxidase inhibitor, tranylcypromine, in depressed patients. Patients were randomized to receive moclobemide (81 patients) or tranylcypromine (79 patients) at individually titrated doses (100-300 mg/day of moclobemide and 10-30 mg/day of tranylcypromine) under double-blind conditions for at least four weeks, in a multicenter trial. Antidepressant efficacy was assessed using items 1-17 of the Hamilton depression rating scale (HAMD-17), the von Zerssen 'Befindlichkeits' scales, a visual analog scale and the clinicians' global impression. Both treatments resulted in significant amelioration of depression as determined by all rating instruments. HAMD-17 scores were reduced by 63% and 58% with moclobemide and tranylcypromine respectively, although the difference between the groups was not significant. The other rating instruments yielded similar results, apart from the clinician's assessment of efficacy at day 28. In this assessment, efficacy was rated as very good/good in 78% of moclobemide treated patients and in 88% of the tranylcypromine treated patients; however, only patients who had not dropped out of the trial were included in this assessment. The tolerability of both drugs was good, although moclobemide appeared to possess a small advantage in this regard since only one patient in this group was prematurely withdrawn from the trial due to inadequate tolerability/adverse events, compared with nine withdrawals in the tranylcypromine group.(ABSTRACT TRUNCATED AT 250 WORDS)

RIMA--a new concept in the treatment of depression with moclobemide.

Moclobemide, a specific reversible inhibitor of monoamine oxidase that shows a preference for the A isoenzyme, has been developed as a new antidepressive agent. Unlike earlier generation monoamine oxidase inhibitors, moclobemide is devoid of any clinically significant tyramine interaction, thus making dietary restrictions during therapy unnecessary. In comparative trials, moclobemide has been found to be superior to placebo and similar to imipramine, clomipramine, and amitriptyline in clinical efficacy. Long-term trials involving moclobemide therapy for up to one year have indicated that antidepressant efficacy can be maintained for this period. Tolerance is good and is significantly better than for tricyclic antidepressants. In addition, unlike the tricyclic antidepressants, overdoses of moclobemide do not appear to be life-threatening.

Efficacy of moclobemide in different patient groups. Results of new subscales of the Hamilton Depression Rating Scale.

Data from 38 double-blind and two single-blind studies with moclobemide vs. placebo and/or standard antidepressants (10 drugs) were available for an intent-to-treat meta-analysis (n = 2,371). In all, 236 subjects received placebo and 1,107 moclobemide. As a measure of efficacy, a > or = 50% decrease from the baseline on the Hamilton Rating Scale for Depression (HAM-D) and its new subscales was taken. Furthermore, the Global Assessment of Efficacy (GAE) was analyzed. New subscales of the HAM-D consist of a retarded depression and an agitation/anxiety scale. The two factors were obtained from factor analyses of 12 x 8 random subsamples resulting in a stable solution. The subjects were subclassified by severity (low, medium, high) prior to treatment. The response to placebo was consistently lower in high scorers. In contrast to that, high scorers on active drugs (moclobemide, imipramine, and clomipramine) showed a tendency to higher response rates. Response rates were, in general, higher on the subscale retarded depression than on agitation/anxiety for both placebo and active drugs. Response rates to moclobemide were highest in unipolar endogenous depressives (66%) followed by bipolars (57%), neurotic depressives (52%), and reactive depressives (43%).

RIMA: a safe concept in the treatment of depression with moclobemide.

Moclobemide--a new, safer antidepressant drug--is described and clinical studies are reviewed. Moclobemide represents a new class of drug, the so-called RIMA compounds--reversible inhibitors of MAO-A. Unlike classical monoamine oxidase (MAO) inhibitors, moclobemide is devoid of hepatotoxicity and has only a slight potentiating effect on the hypertensive action of tyramine; treatment does not require a tyramine-restricted diet. Studies comparing moclobemide with tricyclic antidepressants (TCAs) indicate that moclobemide is significantly better tolerated than TCAs and slightly less well tolerated than placebo.

Long-term treatment with moclobemide. An open-label, non-comparative, multiple-distributed study in patients with a major depressive episode as defined by DSM-III.

Evaluation of 247 patients receiving long-term moclobemide treatment showed that it was effective as an antidepressant, as measured both by decrease in HAMD mean total score and the doctor's evaluation of therapeutic effect. In patients who had been treated for 6 months or less, results were less favourable (ratings of 'very good' or 'good' in 31.5%, compared with 81.3% in patients treated for more than 6 months). This was due to a higher number of drop-outs, as a result of insufficient efficacy in the first 6 months. In those patients who responded favourably, 9.2% relapsed within 6 months of commencing treatment; of the remaining responders, 16% relapsed during months 7-12. In terms of the doctor's evaluation of side-effects, tolerability was 'very good' or 'good' in 88.2%.

Interactions of moclobemide with concomitantly administered medication: evidence from pharmacological and clinical studies.

Interactions may occur on pharmacological or pharmacokinetic grounds. Both types of interactions are discussed in relationship with the pharmacological and pharmacokinetic data of moclobemide, a reversible MAO-inhibitor. A variety of interaction studies either designed more specifically as kinetic or as dynamic studies have been performed with moclobemide. The results of these studies are presented. In view of these results as well as in view of data stemming from clinical trials it can be concluded that apart from interactions with cimetidine and pethidine, moclobemide has been shown to be devoid of relevant interactions.

Efficacy of moclobemide in different patient groups: a meta-analysis of studies.

Whilst tricyclic antidepressants are efficacious in all depressive syndromes, classical MAO-inhibitors differ substantially from them in their action. They are considered less effective in general and not very effective in endogenous depression, but recommended for the treatment of 'atypical' depression. A new class of RIMA (Reversible Inhibitors of MAO-A) represented by moclobemide requires a change in clinical thinking on antidepressants. Moclobemide shows the same efficacy in depression as tricyclics: its effects are similar in unipolar and bipolar affective disorders, and in patients with major depressive episode superimposed on dysthymia (double depression). As with classical antidepressants, the response rate tends to be lower, but is still present in psychotic depression. Agitated depressives do not respond less well than non-agitated patients to moclobemide. Patients meeting DSM-III-R criteria for major depression with melancholia tend to respond better than non-melancholics, but this may be associated with the significantly higher baseline severity observed in melancholics. A slightly higher response rate in patients without concomitant benzodiazepine treatment, compared to those with benzodiazepine comedication, may also be related to baseline differences in the severity of depression. Elderly depressives respond less well than younger patients to classical antidepressants, but with moclobemide, elderly patients do as well as younger ones.

Tolerability of moclobemide, a new reversible inhibitor of monoamine oxidase-A, compared with other antidepressants and placebo.

Moclobemide, a new selective and reversible inhibitor of monoamine oxidase A (RIMA), has been compared with various tricyclic antidepressants (TCAs) in numerous controlled studies. Pooled data from these studies, comprising 1656 patients, as well as the consideration of individual trials, show that moclobemide is far better tolerated than the TCAs. Its side effects mainly comprise mild degrees of nausea and dizziness at the beginning of treatment in a small proportion of patients. Age and sex do not affect the tolerability of moclobemide: it is equally well tolerated by elderly patients. In 2300 patients treated with moclobemide in doses up to 600 mg/day, without dietary restrictions, there was no tyramine-related hypertensive reaction. It is concluded that moclobemide may be the second-generation antidepressant doctors were waiting for--equally effective as the classical antidepressants but far better tolerated.

Efficacy and safety of moclobemide compared with imipramine in the treatment of major depressive disorder. Double-blind multicenter study, Austria.

In a double-blind, 4-week, prospective, randomized multicenter (17 centers) study we checked on the efficacy, tolerability and safety of moclobemide (300-600 mg/d) compared to imipramine (100-200 mg/d) in parallel groups of patients with a Major Depressive Episode (DSM III). The mean % reduction of the HAMD at the end of treatment was 51.7 in the moclobemide group and 52.1 in the imipramine group. The percentage of patients in whom efficacy was globally judged as "good" or "very good" was 62% in the moclobemide group and 60% in the imipramine group. There was no statistically significant difference in the efficacy in both groups but in some factors there was a trend for a better amelioration favoring moclobemide. The final overall physician's judgement of tolerability was "good" or "very good" in 83% of moclobemide patients and in 74% of imipramine patients. Adverse events were reported or observed in 56% of moclobemide patients and in 69% of imipramine patients. The number of mild, moderate and severe adverse events was higher in the imipramine group with a total of 286 versus 189. There was a statistically high significant difference considering the tolerability favoring moclobemide again. In this project the basic goal to find a substance with at least the same efficacy but a much better tolerability for sure got fulfilled.

Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM-III): an Austrian double-blind, multicentre study.

The antidepressant efficacy, tolerability, and safety of moclobemide, a reversible, monoamine oxidase-A inhibitor, were compared with those of imipramine in parallel groups of patients with a major depressive episode, in a 4-week, multicentre (17 centres), randomised study. A total of 381 patients were randomly allocated to either treatment; they were not required to avoid tyramine-rich foods. Drop-out rates were comparable in both groups at about 17%. Judged primarily on the HRSD, no significant differences in efficacy were observed between the groups, but the number of patients presenting with adverse events, as well as the total number of adverse events, was greater with imipramine. Cardiovascular tolerability was satisfactory and physical examination, body weight, and laboratory values were essentially unaffected in both groups.