Sixty out-patients with different nosological types of depression were assigned at random to three different treatment groups and were treated under double-blind conditions for 6 weeks. Two groups received diclofensine in capsules of either 15 or 25 mg, and a third group received capsules with imipramine 25 mg. The dosage schedule provided an initial dose of 2 capsules/day which was to be gradually increased up to a maximum dose of 9 capsules/day. The daily mean dosages actually given over the entire trial period were 64.0 mg diclofensine for group I, 97.6 mg diclofensine for group II, and 102.9 mg imipramine for group III. All treatment groups showed a good improvement of the patients’ clinical states within the 6-week period, but the imipramine-treated patients improved more slowly than the diclofensine-treated patients. This was demonstrated by the mean total scores of the Hamilton Depression Rating Scale (HDRS). Evaluation of different factors of the HDRS yielded differences between the two drugs in favour of diclofensine for the factor ‘inhibition’ from the end of week 1 until the end of week 3 and for the factor ‘somatic complaints’ during week 3. Side effects were – dose dependently – less frequent, less severe, and lasted shorter in the diclofensine-treated patients than in the imipramine-treated ones. The most frequently reported side effects in the diclofensine-treated patients were dry mouth, insomnia, dizziness, and agitation. In the imipramine group side effects were mainly dry mouth, tremor, dizziness, and sleepiness. In conclusion, this study shows an impressively faster onset of efficacy of diclofensine over imipramine, a finding which should be replicated by fu