Effect of Deutetrabenazine on Metabolic Parameters in the Treatment of Tardive Dyskinesia (1953)

Objective: To assess the short- and long-term effects of deutetrabenazine treatment on weight and metabolic parameters in individuals treated for tardive dyskinesia (TD). Background: Deutetrabenazine, a novel vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved by the FDA for treatment of TD in adults. Dopamine-receptor antagonists (DRAs) are associated with worsening of metabolic parameters, including weight gain, hyperlipidemia, and elevated blood glucose. Design/Methods: Two 12-week, randomized placebo-controlled trials (RCTs) of deutetrabenazine for patients with TD evaluated either fixed dosing (AIM-TD; 12, 24, or 36 mg) or dose titration (ARM-TD; max dose, 48 mg/day). Patients completing ARM-TD or AIM-TD were included in an open-label extension (OLE) study, in which all patients underwent response-driven titration of deutetrabenazine from 12 mg/day up to a maximum total dose of 48 mg/day. Weight, body mass index (BMI), serum glucose, serum total cholesterol, and serum triglycerides were evaluated at baseline and during treatment in the RCTs and in the OLE. Results: In the RCTs, 282 and 133 patients received deutetrabenazine or placebo. At baseline, 77% of patients used DRAs. At Week 12, no meaningful changes in weight were observed, with mean (standard error) weight changes of 0.9–1.2 (0.3–0.5) and 0.2 (0.3) kg in the deutetrabenazine and placebo groups, respectively, and mean BMI changes of 0.3–0.5 (0.1–0.2) and 0.1 (0.1) kg/m2. The OLE enrolled 343 patients; no meaningful weight change was observed (mean change: 0.4 [0.4] kg at Week 54 and −0.5 [0.6] kg at Week 106). Across the studies, no meaningful changes were observed in triglyceride, cholesterol, or glucose levels. Conclusions: Deutetrabenazine does not affect common metabolic parameters in patients with TD, even during long-term exposure.