During the clinical development of nomifensine maleate (Merital), 1319 depressed patients received nomifensine (average doses of 150 mg/day) in 4-6 week trials; treatment was continued for at least 2 months in 170 patients and at least 6 months in 53. Comparison data were provided by 593 patients who received placebo and 612 given the tricyclic antidepressant imipramine HCl (average doses of 150 mg/day). The relationship of therapeutic gain to interfering side effects (the therapeutic index) was rated by the investigators and nomifensine received a more favorable therapeutic index rating than did imipramine. Side effect information was collected at each visit. Nomifensine produced less sedating, anticholinergic, and other discomforting side effects than imipramine and was able to sustain clinical benefit with minimal side effects in patients treated up to 6 months.