The efficacy of fluoxetine was evaluated in depressed patients in double-blind imipramine- and placebo-controlled clinical trials. Fluoxetine produced greater improvement than placebo on all major efficacy parameters and was comparable to imipramine with respect to the primary indicators of depression. Fluoxetine had significantly less associated anticholinergic effects, dizziness, drowsiness, somatosensory disturbance, and excessive sweating than imipramine. Although nausea occurred more frequently in fluoxetine patients, it was generally mild and well tolerated. A significantly smaller percentage of fluoxetine than imipramine patients terminated therapy because of adverse experiences.