A randomized, controlled trial of high-dose dextromethorphan in facial neuralgias. (National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD) Neurology 2000;55:964–971.

A randomized, double-blinded, crossover trial compared 6 weeks of oral dextromethorphan with active placebo (low-dose lorazepam) in 19 patients, stratified into three groups: 11 with facial pain and possible trigeminal neuropathy, 5 with anesthesia dolorosa, and 3 with idiopathic trigeminal neuralgia. Dosage was titrated in each patient to the highest level reached without disrupting normal activities. Patients completing the trial included 10 with possible trigeminal neuropathy, 4 with anesthesia dolorosa, and 2 with trigeminal neuralgia. In patients with possible trigeminal neuropathy and anesthesia dolorosa, dextromethorphan decreased pain by a mean of only 2% to 4%, and these estimates were not significant. Both patients with trigeminal neuralgia had more pain during dextromethorphan treatment than during placebo treatment. Of the 3 patients who demonstrated an analgesic response to dextromethorphan during the main trial, only 1 repeatedly responded in 4 subsequent confirmatory drug-placebo crossovers. Conclude dextromethorphan shows little or no analgesic efficacy in pain due to possible trigeminal neuropathy and anesthesia dolorosa. Additional trials are necessary to conclusively evaluate the efficacy of NMDA-receptor antagonists in trigeminal neuralgia.