Citation

Jankovic J, Jimenez-Shahed J, Budman C, Coffey B, Murphy T, Shprecher D, Stamler D. Tremor Other Hyperkinet. Mov. (N Y) 2016; 6.

Copyright

(Copyright © 2016, Center for Digital Research and Scholarship)

DOI

10.5334/TOHM.287

PMID

unavailable

Abstract

BACKGROUND: Deutetrabenazine, an inhibitor of vesicular monoamine transporter type 2 (VMAT2) depletes presynaptic dopamine and is useful in the treatment of hyperkinetic movement disorders. This study explored the safety, tolerability, and preliminary efficacy of deutetrabenazine in adolescents with moderate-to-severe tics associated with Tourette syndrome (TS).

METHODS: In this open-label study of 12-18-year-old patients with TS-related tics, deutetrabenazine was titrated up to 36 mg/day over 6 weeks to adequately suppress tics without bothersome adverse effects (AEs), followed by maintenance at optimal dose for 2 weeks. An independent blinded rater assessed tic severity using the Yale Global Tic Severity Scale (YGTSS), which was the primary outcome measure. Secondary outcome measures included the TS Clinical Global Impression (TS-CGI) and TS Patient Global Impression of Change (TS-PGIC).

RESULTS: Twenty-three enrolled patients received deutetrabenazine and had at least 1 post-baseline YGTSS assessment. The mean (SD [standard deviation]) baseline YGTSS Total Tic Severity Score (TTS) was 31.6 (7.9) and had decreased by 11.6 (8.2) points at week 8, a 37.6% reduction in tic severity (p,0.0001). The TS-CGI score improved by 1.2 (0.81) points (p,0.0001) and the TS-PGIC results at week 8 indicated that 76% of patients were much improved or very much improved compared with baseline. The mean (SD) daily deutetrabenazine dose at week 8 was 32.1 (6.6) mg (range 18-36 mg). One week after withdrawal of deutetrabenazine, the TTS scores increased by 5.6 (8.4) points, providing confirmation of the drug effect. No serious or severe adverse events were reported.

DISCUSSION: The results of this open-label 8-week study suggest that deutetrabenazine is safe and associated with improvement in tic severity in adolescents with TS and troublesome tics. © 2016 Jankovic et al.

Language: en

Keywords

adolescent; adult; human; suicidal behavior; disease severity; fatigue; mental disease; school child; clinical article; headache; somnolence; drug safety; drug efficacy; QT interval; risperidone; diarrhea; drug tolerability; drug withdrawal; irritability; prospective study; electrocardiogram; Gilles de la Tourette syndrome; genotype; tic; Article; drug dose titration; outcome assessment; Clinical Global Impression scale; hyperhidrosis; optimal drug dose; Tics; young adult; rhinopharyngitis; Yale Brown Obsessive Compulsive Scale; Tourette syndrome; attention deficit hyperactivity disorder; Columbia suicide severity rating scale; deutetrabenazine; Deutetrabenazine; disease severity assessment; SD-809; Total Tic Severity Score; VMAT2; Yale Global Tic Severity Scale