In 2013, JAMA Psychiatry published an exciting new finding by Hallak et al1: patients with schizophrenia who were treated with a single infusion of the antihypertensive agent sodium nitroprusside showed a dramatic, instantaneous, and sustained improvement in psychotic and negative symptoms. The study by Hallak et al1 was not only double-blind, randomized, and placebo-controlled, but the authors had also presented a prospective power analysis, ensured good interrater reliability, and reported all the relevant aspects of the trial. Understandably, this study generated tremendous excitement and several attempts were made to replicate the finding. In this issue of JAMA Psychiatry, Brown et al2 report an equally systematic study that fails to replicate the original finding. In fact, the findings by Brown et al2 join those of 2 other prior studies3,4 that also failed to replicate the original finding. A careful analysis of the competing studies fails to reveal an obvious explanation for this discrepancy—except that the original finding was based on a rather small sample of just 10 patients per treatment arm.
Kapur S, Munafò M. Small Sample Sizes and a False Economy for Psychiatric Clinical Trials. JAMA Psychiatry. 2019;76(7):676–677. doi:10.1001/jamapsychiatry.2019.0095
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