The long-term treatment of social phobia with moclobemide.

Patients meeting the social phobia criteria of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) on the DSM-III-R Structured Clinical Interview (n = 101) entered a long-term moclobemide treatment study. These patients were treated for 2 years with moclobemide (phase I) followed by drug withdrawal, in most cases abruptly (phase II). Those who relapsed entered phase III for a further period of 2 years of treatment. During phase I 40 patients (39.6%) withdrew due to inefficacy or relapse. Two patients were removed from the study because of other diagnoses (borderline or schizophreniform). At the end of phase I the remaining patients (58.4%) were rated as not ill (45.5%) or minimally ill (11.9%). Effort was taken to achieve the maximum dose of moclobemide (750 mg/day) and the mean (+/-SD) dose was 723.3 +/- 67.7 mg/day (month 21). A marked decrease in symptoms in the patients who responded was recorded on the Liebowitz Scale for Social Phobia, Clinical Global Impressions. Hamilton Anxiety Scale and Hamilton Depression Scale. Non-response was mainly associated with co-morbidity, especially alcohol abuse, axis II disorders, and a history of major depression or secondary dysthymia. The drug was well tolerated; the more frequent side effects were mild and occurred mainly in the first 2 months of phase I, including nausea, headaches or insomnia. In phase II there was a relapse rate of 88% and 51 patients entered phase III; these patients are still being treated.

Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine.

In a double-blind, parallel group trial, 78 subjects with social phobia received moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or placebo. After eight weeks, both active drugs-phenelzine somewhat more than moclobemide--were clinically and statistically significantly more effective than placebo, as assessed by rating scales. There was some further improvement between weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic. Moclobemide was, however, much better tolerated than phenelzine. Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs.

Moclobemide, imipramine and placebo in the treatment of major depression.

Moclobemide was compared with imipramine and placebo in the treatment of major depressive episodes in 75 outpatients. The dosage of moclobemide (25 patients) was 300 mg daily for the first 5 days, after which it could be increased to 600 mg. Imipramine (25 patients) was given in a dosage starting with 33 mg and gradually increased to 100 mg/day in the first 5 days, after which it could be further increased; 25 patients received placebo. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression, the overall assessment of efficacy and the Zung Self-rating Scale, and clearly superior to placebo; there were no significant differences between the 2 active drugs. Moclobemide was better tolerated than imipramine, and was almost comparable to placebo in this respect.

Moclobemide, imipramine, and placebo in the treatment of major depression (DSM III).

Seventy five patients, diagnosed according to the Structured Clinical Interview for DMS III ("unipolar", Major depression, single or recurrent, with or without melancholia) were treated, in a double-blind fashion, with either moclobemide, imipramine or placebo, during six weeks. The three treatment groups were homogeneous as far as demographic and clinical characteristics were concerned. Patients were in their forties, predominantly females and with long lasting (more than six months) episodes of moderate or severe depressions. From day seven onwards most patients took moclobemide 600 mg/d, imipramine 200 mg/d or 6 caps/d of placebo; only two cases took lower dosages due to intolerance. There were eleven drop-outs, evenly scattered among the three groups. Outcome assessed by means of the Hamilton Scale for Depression and Global Efficacy Evaluations showed a very significant superiority of the two active drugs over placebo. The efficacy of the two drugs was comparable. Side effects were significantly more frequent and more severe in the imipramine group. The tolerability of moclobemide was similar to placebo. These findings are discussed in relation to methodological issues. They point to the conclusion, that moclobemide may be the true "second generation antidepressant", comparably efficacious to the traditional compounds, producing far less side-effects, and because it is reversible, not requiring dietary or drug restrictions in clinical practice.

Tranylcypromine in social phobia.

Thirty-two patients meeting DSM-III criteria for social phobia entered a 1-year drug treatment with tranylcypromine in dosages between 40 and 60 mg/day. After exclusion of the early dropouts, improvement was rated as marked and moderate in 62% and 17% of the sample (N = 29), respectively. Alcohol abuse was associated with a poor outcome. Side effects were frequent and in some cases delayed the attainment of efficacious dosages until the third month of treatment. No serious adverse reactions occurred. The findings, relative to efficacy, are in accordance with a previous trial with phenelzine but need confirmation in double blind controlled studies.

Loxapine versus thioridazine in the treatment of organic psychosis.

Two double-blind trials comparing loxapine and thioridazine were conducted in hospitalized adult males diagnosed as having symptoms of chronic psychosis associated with organic brain syndrome or mental retardation. The drugs were administered orally in the ranges of loxapine 10--150 mg/day and thioridazine 150--750 mg/day for 13 weeks. In the first trial loxapine was found to be generally superior to thioridazine on the Brief Psychiatric Rating Scale, Nurses Observation Scale for In-Patient Evaluation and Clinical Global Impression. The second trial failed to confirm this superiority. The heterogeneity of diagnostic categories included may explain the discrepancy. Extra-pyramidal symptoms and sedative effects were common to both groups and consistent with the pharmacologic profiles of the study drugs.