Alprazolam is the first of the triazolobenzodiazepines to be studied in a large population of depressed patients. In a six-week, double-blind multicenter comparison of alprazolam, imipramine hydrochloride, and placebo in the treatment of 723 patients with depression, the two active drugs were statistically more effective than placebo. Alprazolam was at least as effective as imipramine in relieving depressive symptoms, significantly more effective in relieving somatic symptoms, and showed an earlier onset of activity in some measurements. Anticholinergic side effects were reported most often by patients receiving imipramine, while drowsiness was the only side effect reported most often in the alprazolam group. The Feighner Diagnostic Criteria and prestudy and poststudy intercenter conferences with videotaped patient interviews ensured interrater reliability.
John P. Feighner, Gary C. Aden, Louis F. Fabre, Karl Rickels, Ward T. Smith. Comparison of Alprazolam, Imipramine, and Placebo in the Treatment of Depression. JAMA. 1983;249(22):3057–3064. doi:10.1001/jama.1983.03330460039029