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 toler-ability 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% ([small alpha, Greek] = 0.05 and [small beta, Greek] = 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. The percentage of responders was 80.6 and 89.0% respectively (standard analysis). The CGI of efficacy was similar for the two groups, showing a 70.8% response (complete remission or marked improvement) with the OD group and 79.5% for the TDS group. Additionally, the proportion of patients rated as minimally ill or not ill on the CGI severity of illness at final assessments was not significantly different.
In this study, the antidepressant effect of moclobemide is at least as effective given as an OD dose compared with TDS.The frequencies of occurrence of adverse events were also similar, except that the proportion of patients reporting dizziness on the daily dosing regimen was higher, although there was little difference in severity or duration between the groups. The dizziness was mild and of short duration and did not pose problems clinically. Both dosing regimens were well tolerated. (J Clin Psychopharmacol 1995;15[Suppl 2]:10S-15S)