Use of Tetrabenazine in Huntington Disease Patients on Antidepressants or with Advanced Disease: Results from the TETRA-HD Study ΠPLOS Currents Huntington Disease

Background: The safety and effectiveness of tetrabenazine in different sub-populations of Huntington disease (HD) is not known. We evaluated its safety in individuals on an antidepressant and its effectiveness in advanced HD. Methods: The TETRA-HD study was a randomized, placebo-controlled, double-blind study of 84 individuals with HD who were randomized 2:1 to receive tetrabenazine (54 participants) or placebo (30 participants). We used data from the 12-week randomized controlled study of tetrabenazine to evaluate the incidence of depressed mood either as an adverse event or as a two points or greater worsening on the “depressed mood” item of the Unified Huntington Disease Rating Scale. We also evaluated the effectiveness of tetrabenazine in reducing chorea in advanced HD. Advanced HD was defined as a baseline maximum total chorea score of 19 or greater or as a total functional capacity score of seven or less. Only individuals who were randomized to tetrabenazine (n=54) were included in these analyses. Results:At baseline, 27 (56%) of the 48 participants randomized to tetrabenazine who completed the trial were taking an antidepressant. The incidence of depressed mood did not differ between those taking (15%) and not taking (5%) an antidepressant (p=0.37), and the proportion of individuals experiencing a substantial worsening in their mood scores also did not differ (7% v. 10%; p=1.00). Based on chorea, 14 of the 54 (26%) tetrabenazine participants enrolled had advanced HD, and based on function, 22 (41%) had advanced HD. Chorea declined by 8.1 units among those with baseline scores 19 or greater compared to 4.3 units for those with scores under 19 (p<0.01), but the relative rates of decline did not differ (p=0.62). The decline in chorea did not differ by HD severity as measured by function (p=0.20). Conclusion: In this post hoc analysis, tetrabenazine was not associated with an increased incidence of depressed mood among those taking antidepressants and was effective at reducing chorea in those with advanced HD. Larger, prospective studies are needed to confirm these findings.