Depressed mood and suicidality in individuals exposed to tetrabenazine in a large huntington disease observational study

Background: Tetrabenazine, a treatment for chorea in Huntington disease, carries a boxed warning due to safety, especially related to suicidality. Objective: To compare the frequency of depressed mood and suicidality among a closely monitored cohort of individuals with Huntington disease who were exposed and not exposed to tetrabenazine. Methods: A longitudinal prospective study involving 1360 individuals with HD evaluated at 48 research centers in Australia, Canada, and the United States was examined for frequency of depressed mood that triggered a risk assessment, suicidal thoughts, suicide attempts, and completed suicide among individuals with prior, new, and no exposure to tetrabenazine. Seventy-seven individuals were on tetrabenazine at study enrollment (prior exposure), 64 individuals were exposed to tetrabenazine during the study’s course (new exposure), and 1219 individuals had no exposure to tetrabenazine. Results: The hazard ratio for depressed mood among those with prior exposure to tetrabenazine compared to no exposurewas 0.9 (95% CI, 0.5-1.6) and for those with new exposure compared to no exposure was 1.2 (95% CI, 0.8-1.9). One individual (1.3%) with prior exposure, one individual (1.6%) with new exposure, and 35 individuals (2.9%) with no exposure to tetrabenazine reported suicidal thoughts. The hazard ratio for suicidal ideation among those with prior exposure to tetrabenazine compared to no exposure was 0.5 (95% CI, 0.1-3.8) and for those with new exposure to tetrabenazine compared to no exposure was 0.6 (95% CI, 0.1-4.4). Among individuals with prior or new exposure to tetrabenazine, no suicide attempts or suicides occurred. Among those with no exposure to tetrabenazine 17 suicide attempts (1.4%) and four suicides (0.3%) occurred. Conclusions: In a large observational study with close clinical supervision, tetrabenazine treatment was not associated with an increased risk of depressed mood, suicidal ideation, suicide attempts, or suicide.