Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic features

Helena K Kim; Aristotle N Voineskos; Nicholas H Neufeld; George S Alexopoulos; Kathleen S Bingham; Alastair J Flint; Patricia Marino; Anthony J Rothschild; Ellen M Whyte; Benoit H Mulsant

doi:10.1038/s41380-024-02523-7

Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic features

Mol Psychiatry. 2024 Mar 19. doi: 10.1038/s41380-024-02523-7. Online ahead of print.

Authors

Helena K Kim¹, Aristotle N Voineskos^{1

2}, Nicholas H Neufeld^{1

2}, George S Alexopoulos^#³, Kathleen S Bingham^#^{1

4}, Alastair J Flint^#^{1

4}, Patricia Marino^#³, Anthony J Rothschild^#⁵, Ellen M Whyte^#⁶, Benoit H Mulsant^{7

8}

Affiliations

¹ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
² Centre for Addiction and Mental Health, Toronto, ON, Canada.
³ Department of Psychiatry, Weill Cornell Medicine of Cornell University and New York Presbyterian Hospital, Westchester Division, New York, NY, USA.
⁴ Centre for Mental Health, University Health Network, Toronto, ON, Canada.
⁵ University of Massachusetts Chan Medical School and UMass Memorial Health Care, Worcester, MA, USA.
⁶ Department of Psychiatry, University of Pittsburgh School of Medicine and UPMC Western Psychiatric Hospital, Pittsburgh, PA, USA.
⁷ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. benoit.mulsant@utoronto.ca.
⁸ Centre for Addiction and Mental Health, Toronto, ON, Canada. benoit.mulsant@utoronto.ca.

^# Contributed equally.

PMID: 38503927
DOI: 10.1038/s41380-024-02523-7

Abstract

Some data suggest that antipsychotics may adversely affect brain structure. We examined the relationship among olanzapine exposure, relapse, and changes in brain structure in patients with major depressive disorder with psychotic features. We analyzed data from the Study of the Pharmacotherapy of Psychotic Depression II trial (STOP-PD II), a randomized, placebo-controlled trial in patients with psychotic depression who attained remission on sertraline and olanzapine and were randomized to continue sertraline plus olanzapine or placebo for 36 weeks. Olanzapine steady state concentration (SSC) were calculated based on sparsely-sampled levels. Rates of relapse and changes in brain structure were assessed as outcomes. There were significant associations between dosage and relapse rates (N = 118; HR = 0.94, 95% CI [0.897, 0.977], p = 0.002) or changes in left cortical thickness (N = 44; B = -2.0 × 10^-3, 95% CI [-3.1 × 10^-3, -9.6 × 10^-4], p < 0.001) and between SSC and changes in left cortical thickness (N = 44; B = -8.7 × 10^-4, 95% CI [-1.4 × 10^-3, -3.6 × 10^-4], p = 0.001). Similar results were found for the right cortex. These associations were no longer significant when the analysis was restricted to participants treated with olanzapine. Our findings suggest that, within its therapeutic range, the effect of olanzapine on relapse or cortical thickness does not depend on its dosage or SSC. Further research is needed on the effect of olanzapine and other antipsychotics on mood symptoms and brain structure.