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Original Investigation
August 20, 2019

Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission: The STOP-PD II Randomized Clinical Trial

Author Affiliations
  • 1Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  • 2Centre for Mental Health, University Health Network, Toronto, Ontario, Canada
  • 3Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, Westchester Division, New York
  • 4University of Massachusetts Medical School and UMass Memorial Health Care, Worcester
  • 5Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 6National Institute of Mental Health, Bethesda, Maryland
  • 7Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York
  • 8Centre for Addiction and Mental Health, Toronto, Ontario, Canada
JAMA. 2019;322(7):622-631. doi:10.1001/jama.2019.10517
Key Points

Question  Does continuing antipsychotic medication reduce the risk of relapse among patients with psychotic depression in remission?

Findings  In this 36-week randomized clinical trial that included 126 persons aged 18 years or older, 13 participants (20.3%) randomized to sertraline plus olanzapine and 34 (54.8%) to sertraline plus placebo experienced a relapse, a difference that was statistically significant.

Meaning  For patients with psychotic depression in remission, continuing olanzapine reduced the 36-week risk of relapse.

Abstract

Importance  Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission.

Objective  To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent.

Design, Setting, and Participants  Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017.

Interventions  Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline.

Main Outcomes and Measures  The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c).

Results  Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, −0.01 to 0.10), high-density lipoprotein cholesterol (−0.01 mg/dL; 95% CI, −0.03 to 0.01), triglyceride (−0.153 mg/dL; 95% CI, −0.306 to 0.004), glucose (−0.02 mg/dL; 95% CI, −0.12 to 0.08), or HbA1c levels (−0.0002 mg/dL; 95% CI, −0.0021 to 0.0016).

Conclusions and Relevance  Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain.

Trial Registration  ClinicalTrials.gov Identifier: NCT01427608

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