In a six week, double-blind, parallel study of alprazolam and amitriptyline hydrochloride in 130 outpatients suffering from moderate to severe nonpsychotic depression, alprazolam was as effective as amitriptyline hydrochloride in relieving depressive symptoms and significantly more effective in relieving symptoms of anxiety and somatization. Alprazolam showed an earlier onset of activity in most measurements of efficacy and produced fewer side effects than amitriptyline hydrochloride. Anticholinergic side effects were reported more frequently by patients taking amitriptyline hydrochloride, while drowsiness was reported more frequently by patients taking alprazolam. At the end of the study, the average daily doses were 2.4 mg alprazolam and 135 mg amitriptyline hydrochloride. The Hamilton Psychiatric Rating Scale for Depression, Hamilton Anxiety Rating Scale, Physician's Global Impressions, Patients' Global Impressions, Hopkins Self-Rating Symptom Scale, and Symptom and Side Effects Checklist were evaluated at the end of weeks 1, 2, 3 and 6 to determine and compare the efficacy and safety of the two study drugs.