The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d). The primary outcome measure was the 24-item Hamilton Depression Rating Scale total score. For trial 1, endpoint improvement for the OLZ group (−14.9) was not significantly different from the PLA or OFC groups. The OFC group had significantly greater endpoint improvement (−20.9) than the PLA group (−10.4, P = 0.001); this significant difference was present within 7 days of therapy and maintained at every subsequent visit. The OFC group also had significantly higher response rate (63.6%) than the PLA (28.0%, P = 0.004) or OLZ (34.9%, P = 0.027) groups. For trial 2, there were no significant differences among treatment groups on the 24-item Hamilton Depression Rating Scale total scores or response rates. The combination exhibited a comparable safety profile with OLZ monotherapy and no significant increases in extrapyramidal symptoms compared with placebo. Patients with major depression with psychotic features treated with OLZ monotherapy did not demonstrate significant depressive symptom improvement compared with placebo in either trial; however, an olanzapine/fluoxetine combination was associated with significant improvement compared with placebo in one trial and was well tolerated.
*Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA; †Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN; ‡Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont,MA and §Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA.
Received June 9, 2003; accepted after revision March 1, 2004.
Portions of this study were presented at the Society of Biological Psychiatry Annual Meeting, May 2001; the American Psychiatric Association Annual Meeting, May 2001; and the World Congress of Biological Psychiatry Annual Meeting, July 2001.
Address correspondence and reprint requests to Anthony J. Rothschild, MD, Department of Psychiatry, University of Massachusetts Medical School, 361 Plantation Street, Worcester, MA 01605. E-mail: RothschA@ummhc.org.