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An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder

Simeon, Daphne MD; Knutelska, Margaret PhD

Journal of Clinical Psychopharmacology: June 2005 - Volume 25 - Issue 3 - p 267-270
doi: 10.1097/
Brief Reports

Abstract: Depersonalization disorder (DPD) remains one of the few disorders in modern psychiatry for which no treatments are established that are even partially effective, whether pharmacological or psychotherapeutic. Depersonalization disorder is a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition dissociative disorder characterized by a pervasive subjective sense of unreality and detachment with intact reality testing. Two recent controlled medication trials, one with lamotrigine and one with fluoxetine, failed to show efficacy. There is some evidence for dysregulation of endogenous opioid systems in depersonalization, and a few studies have suggested that opioid antagonists may have efficacy in the treatment of dissociation and depersonalization symptoms. In this prospective open treatment trial, 14 subjects were recruited and treated with naltrexone for 6 weeks to a maximum dose of 100 mg/d (first 7 subjects) or 10 weeks to a maximum dose of 250 mg/d (next 7 subjects). Mean naltrexone dose was 120 mg/d. There was an average 30% reduction of symptoms with treatment, as measured by 3 validated dissociation scales. Three patients were very much improved, and 1 patient was much improved with naltrexone treatment. These findings are potentially promising in a highly treatment-refractory disorder for which no treatment guidelines exist and warrant a randomized controlled trial.

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY.

Received June 4, 2004; accepted after revision December 28, 2004.

Address correspondence and reprint requests to Daphne Simeon, MD, Department of Psychiatry, Box 1230, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029. E-mail:

© 2005 Lippincott Williams & Wilkins, Inc.