28 Feb Antipsychotic Medication Linked to Brain Cortex Thinning in People in Remission from Psychotic Depression
MedicalResearch.com Interview with:
Dr. Aristotle Voineskos MD, PhD, FRCPC
Director, Slaight Family Centre for Youth in Transition and Head,
Kimel Family Translational Imaging-Genetics Laboratory
Campbell Family Mental Health Research Institute
University of Toronto
MedicalResearch.com: What is the background for this study?
Response: Uncontrolled studies in humans have shown conflicting results regarding effects of antipsychotic medications on brain structure. Recent studies in animals (e.g. rats and non-human primates) show that these medications may be associated with brain volume loss. To date, our knowledge of the effects of antipsychotic medications on brain structure in humans have been limited by the lack of a double-blind, randomized, placebo-controlled trial with brain imaging. Ours is the first such study. It is considered unethical to do such a study in people with schizophrenia, because of the life-saving benefits of these medications in this illness. However, in people with depression also experiencing psychosis, it was possible to do such a study once people experienced remission from their illness.
MedicalResearch.com: What are the main findings?
Response: The main findings are that antipsychotic medication compared to placebo is associated with a thinning of the cortex in people who are in remission from psychotic depression (both groups were on sertraline, an antidepressant).
The secondary finding was that there was a possible (weaker) effect in the white matter connections of the brain. However, for those people who experienced relapse (i.e. a return of depression and psychosis), while on placebo, their cortex also showed thinning, suggesting that active illness may also affect brain structure.
MedicalResearch.com: What should readers take away from your report?
Response: When psychosis is present, antipsychotics remain the cornerstone of treatment, and the brain imaging data from this study further support that recommendation. However, in people who will not or do not experience psychosis, the risk/benefit analysis for prescribing an antipsychotic may change based on our results. This may be especially true in older people, where the brain is more vulnerable, and in whom we found larger effects of the antipsychotic on cortical thinning.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: It would be important to understand if this is a reversible change. It would also be important to conduct this study in children and adolescents, where like in older people, the brain is changing rapidly, and may be more vulnerable. It would be important to see if our findings apply to all antipsychotic medications. And finally, it would be important to understand if these brain changes are associated with any cognitive (i.e. memory etc.) or other behavioral changes.
MedicalResearch.com: Is there anything else you would like to add?
Response: We are in great need of carefully controlled studies to better understand our existing treatments and potentially new ones, that also include a ‘read-out’ of their effects on the brain. This can help accelerate progress, better tailor our treatments to those who need them, and give hope to the many people suffering from mental illness.
The work in this study was funded by the National Institute of Mental Health. Full disclosures for all authors are listed in the journal article.
Voineskos AN, Mulsant BH, Dickie EW, et al. Effects of Antipsychotic Medication on Brain Structure in Patients With Major Depressive Disorder and Psychotic Features: Neuroimaging Findings in the Context of a Randomized Placebo-Controlled Clinical Trial. JAMA Psychiatry. Published online February 26, 2020. doi:10.1001/jamapsychiatry.2020.0036
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