To the Editor In the secondary analysis of a double-blind discontinuation randomized clinical trial of adjunctive olanzapine vs placebo on top of sertraline, Voineskos et al1 reported that antipsychotic medication reduces brain gray matter volume and where alternatives are present, antipsychotics should be avoided.
In fact, there are no alternatives with solidly proven efficacy, and phrases like this could be misleading especially because more patients under the discontinuation arm manifested a relapse although they had previously achieved sustained remission. The complete picture of the results (4 groups defined by treatment and relapse status) seems more complex, but the authors do not report them in sufficient detail. Among patients in relapse, those in the placebo group had worse findings compared with those in the olanzapine group, which might mean olanzapine exerted a neuroprotective effect independent of its antipsychotic effect. What is puzzling is that patients in the olanzapine group performed better when there was a significant brain gray matter volume loss. This raises the question whether antipsychotic-induced cortical thickness reduction is related to treatment response and whether such a correlation reflects a causal relationship and is not spurious. Gray matter loss is not always a bad thing; it transiently happens also during normal conditions, eg, during pregnancy.2
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Fountoulakis KN. Brain Volume Changes Under Treatment With Antipsychotics. JAMA Psychiatry. 2020;77(8):876–877. doi:10.1001/jamapsychiatry.2020.1358
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