Diclofensine inhibits the uptake of serotonin, noradrenaline and dopamine. In a controlled study, out-patients suffering from moderate to severe depression were treated with the objective of assessing the new drug's therapeutically effective dose range. Maprotiline was used as a reference drug: fourteen patients were assigned to receive diclofensine and thirteen to receive maprotiline in a double-blind design. Depending on tolerance and efficacy, they were treated for periods ranging from 5 to 150 days. Doses were titrated to the optimum. Findings suggest that a 50 mg daily dose of diclofensine would be sufficient for the majority of the patients. The dosage can be safely increased up to 150 mg daily but this offers few therapeutic advantages. While the efficacy index of the two drugs was similar (approximately 60% ), they differed greatly in their profile of side-effects. No signs of abrupt dissipation of the achieved clinical effects were observed during continued treatment, and no withdrawal reactions were observed when the treatment was stopped. The new drug may be more effective in treating patients in whom a psycho-energizing and mood alleviating effect is desired.