Moclobemide vs. imipramine in bipolar depression: a multicentre double-blind clinical trial

Objective: To determine the relative efficacy, tolerability and risk of precipitating mania of moclobemide and imipramine in the treatment of bipolar depression. Method: A randomized, double-blind, parallel group, multicentre study of moclobemide (MCB) (450-750 mg daily) and imipramine (IMI) (150-250 mg daily) in 21 centres in nine countries; 156 patients (65 males, 91 females) aged 18-65 with bipolar depression (17-item Hamilton Depression Rating Scale (HAMD) score greater than or equal to 16) participated. Clinical status was assessed using standardized rating scales before treatment and at 1,2,3,4,6 and 8 weeks. The data were analysed on an intention to treat basis with the last observation carried forward. Results: In the MCB group, the mean HAMD fell from 23.0 to 13.1, in the IMI group it fell from 22.5 to 9.5; the mean score on the Montgomery-Asberg Depression Rating Scale (MADRS) fell from 29.5 to 16.3 on MCB and from 29.2 to 11.6 on IMI. There were no statistically significant differences between the two groups on any efficacy measures. Anticholinergic side-effects were three times more common with IMI than MCB and weight gain was also greater on IMI. Two patients (3.7%) on MCB and six patients (11%) on IMI were withdrawn because of manic symptoms, with manic symptoms occurring earlier on IMI, although these differences did not reach statistical significance. Conclusion: No differences in efficacy were detected between MCB and IMI in the treatment of bipolar depression. The data suggests that MCB is less likely than IMI to precipitate mania.