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Comments and Controversies

Reserpine for schizophrenia

Vol. 10, No. 09 / September 2011

It seems unfortunate “Treatment-resistant schizophrenia: What can we do about it?” (Current Psychiatry, June 2011, p. 52-59) made no mention of reserpine, an alternative antipsychotic with a completely different mechanism of action. Many articles have reported augmentation when reserpine is combined with D2-blocking antipsychotics. Several articles also document a lack of convincing evidence for the common opinion that reserpine causes or worsens depression. Many psychiatrists may not know it is still available for prescription.

Dale Simpson, MD
Psychiatrist, Private Practice
Sanford, NC

Dr. Citrome responds

Thank you for bringing up an agent that has been forgotten but played a pivotal role in the early history of the psychopharmacology of schizophrenia. I could not locate a report of a randomized controlled study of reserpine specifically for treatment-resistant or refractory schizophrenia; therefore, I did not include this agent in my review. Christison et al1 published a succinct summary of the use of reserpine in schizophrenia in which they reviewed the extant controlled studies for reserpine for psychosis. All were conducted more than 50 years ago using the standards for such trials as they existed at that time. The authors comment there is anecdotal and uncontrolled evidence that some patients who respond poorly to “neuroleptics” improve with reserpine. They suggest trials of reserpine may be warranted in some neuroleptic-resistant patients but effects such as severe depression, significant hypotension, exacerbation of asthma, peptic ulceration and hemorrhage, and extrapyramidal side effects can be problematic. There is evidence that a gradual increase to a full dose reduces some side effects.

Leslie Citrome, MD, MPH
Professor of Psychiatry
New York University School of Medicine
New York, NY


1. Christison GW, Kirch DG, Wyatt RJ. When symptoms persist: choosing among alternative somatic treatments for schizophrenia. Schizophr Bull. 1991;17(2):217-245.

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