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Dextromethorphan Mitigates Phantom Pain in Cancer Amputees

From the Post-Anesthesia Care Unit and Acute Pain Service, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Correspondence: Address correspondence and reprint requests to: Avi A. Weinbroum, MD, Post-Anesthesia Care Unit, Tel-Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel; Fax: 972-3-692-5749; E-mail: draviw{at}tasmc.health.gov.il

Background: Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors may play a role in the persistence of phantom pain. Dextromethorphan (DM) blocks NMDA receptors.

Methods: Eight cancer and two noncancer amputees with established, disabling phantom pain received oral DM 60 or 90 mg twice daily (BID) in a three-period double-blind crossover placebo-controlled trial. This followed an open-phase trial in which either dose was given three times daily if pain relief during the double-blind phase was <50% of pretreatment intensity. Patients then underwent a 3-month phase of treatment with the best regimen and a subsequent 1-month posttreatment follow-up.

Results: All patients reported a >50% decrease in pain intensity, better mood, and lower sedation in each treatment phase. Four individuals reported this level of pain relief with the 60-mg and one with the 90-mg BID regimen during the double-blind phase, whereas two amputees benefited from the 60-mg and three from the 90-mg thrice-daily regimen in the open-phase trial. One reported exacerbation of pain with the 90-mg BID regimen, and three reported pain rebound at the 1-month posttreatment follow-up phase. Three patients stopped all previous analgesic use during the study.

Conclusions: Persistent phantom pain probably involves NMDA receptor hyperexcitability because DM 120 to 270 mg/day mitigated the pain satisfactorily.

Key Words: Pain • Phantom • NMDA receptor • Antagonist • Dextromethorphan

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