An open label trial of dextromethorphan in Huntington's disease

Because of its interactions at N-methyl-D-aspartate and haloperidol specific sigma receptors, dextromethorphan may have symptomatic or protective effects in Huntington's Disease (HD). Escalating doses of dextromethorphan in 11 HD patients produced side effects of dysarthria, rash, and incoordination. At maximum doses, performance declined on a variety of measures of HD, including functional rating scales and quantitative exam scores, consistent with dose-related side effects. Windows of symptomatic benefit were not found. Serum levels of dextromethorphan and its metabolites, including the active compound dextrorphan, showed atypical relationships to dose and side effects, suggesting complex pharmacokinetics. Although not beneficial symptomatically, further trials of dextromethorphan as protective therapy in HD may be warranted.