A comparison of the efficacy and tolerability of moclobemide given as a single daily dose or in three divided doses per day for the treatment of patients with a major depressive episode (DSM-III-R).

This was a prospective, double-blind, randomized, multicenter trial comparing moclobemide once daily (OD) with three times daily (TDS) dosing. The duration of the study was 6 weeks with the initial dose of moclobemide being 450 mg/day (either 450 mg in the morning or 150 mg three times daily). Placebo tablets were used to ensure that the study was double blind. After 2 weeks, the dose could be increased to 600 mg/day if tolerability was acceptable and efficacy was judged insufficient by the investigator. Patients were assessed at baseline and at days 3, 7, 14, 21, 28, and 42. Efficacy was primarily judged on the Hamilton Rating Scale for Depression (HAM-D) (17item). Patients had to score at least 17 to enter the study. Safety and tolerability were judged on reported adverse events, safety parameters, premature withdrawals, and a physicians' global tolerability rating. There were also three secondary efficacy parameters--the Hamilton Rating Scale for Anxiety, Visual Analogue Scales for pain and irritability, and physicians' Clinical Global Impression (CGI). A total of 130 evaluable patients were required to detect a difference of more than 20% (alpha = 0.05 and beta = 0.8) between groups. A total of 189 patients entered the study, and the standard analysis comprised 145 patients. The efficacies between the two dosing regimens as determined by the HAM-D score and from the CGI were found not to differ significantly. For the standard analysis population, there was a reduction in mean HAM-D of 73.8 and 72.9% for the OD and TDS groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)