Comparison of two-phase treatment with imipramine or fluvoxamine, both followed by lithium addition, in inpatients with major depressive disorder.

OBJECTIVE This study was designed to compare the efficacy of two two-phase pharmacological treatment strategies for inpatients with DSM-IV major depressive disorder. METHOD During phase I, patients participated in a double-blind study of the effects of imipramine versus fluvoxamine, with final evaluation of response 4 weeks after patients attained the target plasma level. In phase II, for patients without treatment response or with partial response in phase I, lithium was added to imipramine or fluvoxamine. Final evaluation of response was made 3 weeks after the patients attained the target plasma level of lithium (0.6-1.0 mmol/liter). RESULTS One hundred thirty-eight patients were enrolled in the study. At the end of phase I, remission, defined as a final Hamilton Depression Rating Scale score < or =7, was achieved by 16 (23%) of 70 imipramine-treated patients and 10 (15%) of 68 fluvoxamine-treated patients. At the end of phase II, 41 (59%) of 70 imipramine-treated patients versus 27 (40%) of 68 fluvoxamine-treated patients qualified for remission, a significant difference in favor of the imipramine strategy. Only a small minority of both groups received concomitant medication. In both phase I and phase II, the discontinuation rate was low (5% and 10%, respectively). CONCLUSIONS Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine for treatment of severely depressed inpatients. Both strategies were well tolerated.