Deutetrabenazine in Tics Associated with Tourette Syndrome

Joseph Jankovic, Joohi Jimenez-Shahed, Cathy Budman, Barbara Coffey, Tanya Murphy, David Shprecher, David Stamler, Joseph Jankovic, Joohi Jimenez-Shahed, Cathy Budman, Barbara Coffey, Tanya Murphy, David Shprecher, David Stamler

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.

Keywords: SD-809; Tics; Tourette syndrome; VMAT2; deutetrabenazine.

Conflict of interest statement

Funding: This report describes a study funded by Auspex, a wholly owned subsidiary of Teva Pharmaceutical Industries, Petah Tikva, Israel. Conflict of Interest: The authors report no conflict of interest. Ethics Statement: The study was conducted in accordance with the principles of Good Clinical Practice, and with the FDA guidelines on safety monitoring by Institutional Review Boards for Human Research. Written informed consent by parent/guardian and assent of the adolescent was obtained before study participation. This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent.

Figures

Figure 1. Study Design. Timeline of in-person…
Figure 1. Study Design. Timeline of in-person and telephone visits and a list of assessments at each visit. Abbreviations: YGTSS, Yale Global Tic Severity Scale; TS-CGI, Tourette’s Syndrome Clinical Global Impression; PGIC, Patient Global Impression of Change (administered at weeks 2, 4, 8, and 9 only), CY-BOCS, Children’s Yale–Brown Obsessive–Compulsive Scale; BDI-II, Beck Depression Inventory; C-SSRS, Columbia Suicide Severity Rating Scale.
Figure 2. Changes in Total Tic, Motor,…
Figure 2. Changes in Total Tic, Motor, and Phonic Tic Scores over Time. Primary efficacy scores were change in mean TTS scores at week 8 following 6 weeks of titration and 2 weeks maintenance dosing with deutetrabenazine. The graph illustrates a reduction in TTS, motor and phonic tic mean scores to week 8 (all p
Figure 3. TS-CGI Score Reductions at Week…
Figure 3. TS-CGI Score Reductions at Week 8. Physician ratings of clinical improvement following deutetrabenazine treatment are graphically presented with the number and percentage of patients with score rating reductions by 1, 2, and 3 points occurring between baseline and week 8 TS-CGI assessments. Abbreviations: TS-CGI: Tourette’s Syndrome Clinical Global Impression Scale.
Figure 4. TS-PGIC Scores at Week 8.…
Figure 4. TS-PGIC Scores at Week 8. Patient rating in the Tourette Syndrome Patient Global Impression of Change (TS-PGIC).

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