Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic ... - Nature.com
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.
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Data availability
Data available upon request.
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Acknowledgements
We thank the members of the STOP-PD II Study Group for their contributions. Members of the STOP-PD II Study Group are listed in the Supplementary Information.
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All authors made substantial contributions to the design of the study, data acquisition, data analysis, interpretation, and/or preparation of the manuscript. All authors participated in drafting and revising of the manuscript and approved the final version to be published.
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HKK has no financial relationships with commercial interests. ANV receives funding from the National Institute of Mental Health (NIMH), Canadian Institutes of Health Research, Canada Foundation for Innovation, Centre for Addiction and Mental Health (CAMH) Foundation, and the University of Toronto. NHN receives grant support from th...
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