Volume 28, Part 1

Double-Blind Crossover Study of Mirtazapine, Amitriptyline and Placebo in Patients with Major Depressive Disorder

Ahsan Y. Khan, MD

Dr. Khan is Associate Professor, Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, Wichita, KS.

Mark L. Catterson, MD

Dr. Catterson is in private practice in Manhattan, KS.

Sheldon H. Preskorn, MD

Dr. Preskorn is Professor and Chairman, Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, Wichita, KS.

Abstract

This crossover study was a follow-up protocol for patients who did not respond following a double-blind, random assignment, six week trial of the antidepressant efficacy of mirtazapine versus amitriptyline versus placebo (i.e., the lead-in study). Nonresponse in the lead-in study was defined as less than a 50% reduction in symptom severity as measured by a 17- item Hamilton Depression Rating Scale after six weeks of treatment. Patients who had not responded to placebo (n = 73) or amitriptyline (n = 46) were crossed over in a double-blind fashion to treatment with mirtazapine while patients who had not responded to mirtazapine (n = 51) were crossed over to treatment with amitriptyline. At the end of eight weeks of crossover treatment the response rate based on last observation carried forward analysis was 64% (48/73) and 54% (25/46) respectively for the placebo and amitriptyline nonresponders crossed over to mirtazapine and 37% (19/51) for the mirtazapine nonresponders crossed over to amitriptyline. The completion rate was 88% (64/73) and 85% (39/46) respectively for placebo and amitriptyline nonresponders crossed over to mirtazapine and 69% (35/51) for mirtazapine nonresponders crossed over to amitriptyline. Based on this crossover study, there appears to be patients with major depression who respond differentially to mirtazapine versus amitriptyline.