Deutetrabenazine in Tics Associated with Tourette Syndrome

Jankovic, Joseph; Jimenez‐Shahed, Joohi; Budman, Cathy L.; Coffey, Barbara J.; Murphy, Tanya K.; Shprecher, David; Stamler, David

doi:10.7916/d8m32w3h

Cited by 22 publications

(10 citation statements)

References 27 publications

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“…Doses were selected based on population pharmacokinetic modeling of deutetrabenazine’s active metabolites. Based on robust pharmacokinetic sampling data from a previous pilot study, a population pharmacokinetic model was created to simulate total metabolite exposure across a range of pediatric and adolescent body weights to guide dose selection.…”

Section: Methodsmentioning

confidence: 99%

“…Deutetrabenazine, a vesicular monoamine transporter type 2 inhibitor, is approved by the US Food and Drug Administration for the treatment of chorea associated with Huntington disease and tardive dyskinesia in adults . Results from an open-label, phase 1b study showed that adolescents with troublesome motor and phonic tics associated with Tourette syndrome who received deutetrabenazine and were titrated up to 36 mg per day experienced a mean reduction in Yale Global Tic Severity Scale–Total Tic Score (YGTSS-TTS) of 11.6 points after 8 weeks of treatment, representing a 37.6% reduction in tic severity from baseline . Based on these positive preliminary results, clinical development of deutetrabenazine was continued in the Alternatives for Reducing Tics in Tourette Syndrome (ARTISTS) program, which included 2 randomized, placebo-controlled trials (ARTISTS 1 and ARTISTS 2) and a long-term open-label extension study (ARTISTS).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome

et al. 2021

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IMPORTANCE Tourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics, often accompanied by behavioral and psychiatric comorbidities.Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved in the US for the treatment of chorea associated with Huntington disease and tardive dyskinesia. OBJECTIVETo report results of the ARTISTS 2 (Alternatives for Reducing Tics in Tourette Syndrome 2) study examining deutetrabenazine for treatment of Tourette syndrome. DESIGN, SETTING, AND PARTICIPANTS This phase 3, randomized, double-blind, placebocontrolled, parallel-group, fixed-dose study was conducted over 8 weeks with a 1-week follow-up (June 21, 2018, to December 9, 2019). Children and adolescents aged 6 to 16 years with a diagnosis of Tourette syndrome and active tics causing distress or impairment were enrolled in the study. Children were recruited from 52 sites in 10 countries. Data were analyzed from February 4 to April 22, 2020. INTERVENTIONS Participants were randomized (1:1:1) to low-dose deutetrabenazine (up to 36 mg/d), high-dose deutetrabenazine (up to 48 mg/d), or a matching placebo, which were titrated over 4 weeks to the target dose followed by a 4-week maintenance period. MAIN OUTCOMES AND MEASURES The primary efficacy end point was change from baseline to week 8 in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) for high-dose deutetrabenazine. Key secondary end points included changes in YGTSS-TTS for low-dose deutetrabenazine, Tourette Syndrome Clinical Global Impression score, Tourette Syndrome Patient Global Impression of Impact score, and Child and Adolescent Gilles de la Tourette Syndrome-Quality of Life Activities of Daily Living subscale score. Safety assessments included incidence of treatment-emergent adverse events, laboratory parameters, vital signs, and questionnaires. RESULTSThe study included 158 children and adolescents (mean [SD] age, 11.7 [2.6] years). A total of 119 participants (75%) were boys; 7 (4%), Asian; 1 (1%), Black; 32 (20%), Hispanic; 4 (3%), Native American; 135 (85%), White; 2 (1%), multiracial; 9 (6%), other race; and 1 (0.6%), of unknown ethnic origin. Fifty-two participants were randomized to the high-dose deutetrabenazine group, 54 to the low-dose deutetrabenazine group, and 52 to the placebo group. Baseline characteristics for participants were similar between groups. Of the total 158 participants, 64 (41%) were aged 6 to 11 years, and 94 (59%) were aged 12 to 16 years at baseline. Mean time since Tourette syndrome diagnosis was 3.3 (2.8) years, and mean baseline YGTSS-TTS was 33.8 (6.6) points. At week 8, the difference in YGTSS-TTS was not significant between the high-dose deutetrabenazine and placebo (continued) Key Points Question Are fixed doses of deutetrabenazine up to 48 mg per day safe and effective for the treatment of tics associated with Tourette syndrome in pediatric patients? Findings In this randomized clinical trial of 158 children and adolescents, differences in tic severity b...

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome

et al. 2021

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“…Based on robust pharmacokinetic sampling data from a previous pilot study, a population pharmacokinetic model was developed to guide dose selection by modeling deutetrabenazine’s active metabolites and simulating total metabolite exposure across a range of body weights corresponding to a pediatric and adolescent population. Maximum total daily doses of deutetrabenazine were 48 mg/d (24 mg twice daily) for patients weighing 40 kg or more, 42 mg/d (21 mg twice daily) for patients weighing 30 to less than 40 kg, and 30 mg/d (15 mg twice daily) for patients weighing 20 to less than 30 kg.…”

Section: Methodsmentioning

confidence: 99%

“…Deutetrabenazine is a VMAT2 inhibitor approved by the US Food and Drug Association (FDA) to treat chorea associated with Huntington disease and TD in adults . In a pilot study in adolescents with TS, deutetrabenazine was generally well tolerated and significantly reduced tic severity . Based on these results, clinical development of deutetrabenazine was continued in the Alternatives for Reducing Tics in TS (ARTISTS) program.…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Flexible-Dose Deutetrabenazine in Children and Adolescents With Tourette Syndrome

et al. 2021

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IMPORTANCETourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics; treatments for tics are associated with safety concerns. Deutetrabenazine is a selective vesicular monoamine transporter 2 inhibitor approved for the treatment of chorea associated with Huntington disease and tardive dyskinesia in adults. OBJECTIVE To examine whether deutetrabenazine is effective and safe for the treatment of Tourette syndrome in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS This phase 2/3, randomized, double-masked, placebocontrolled, parallel-group, dose-titration study included children and adolescents (aged 6-16 years) with Tourette syndrome with active tics causing distress or impairment (ie, Yale Global Tic Severity Scale-Total Tic Score [YGTSS-TTS] Ն20). The trial was conducted over 12 weeks, with 1 week of

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“…Deutetrabenazine is an isomer of tetrabenazine with a longer half-life and less risk of side effects [ 77 •]. Open-label studies have demonstrated that deutetrabenazine is safe and effective for tic disorders [ 89 ]. However, the phase 2/3 ARTIST1 and phase 3 ARTIST2 trials failed to reach the primary end point of tic reduction (NCT03567291, NCT03571256).…”

Section: Pharmacologic Interventionsmentioning

confidence: 99%

Tourette Syndrome Treatment Updates: a Review and Discussion of the Current and Upcoming Literature

Frey

Malaty

2022

Curr Neurol Neurosci Rep

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Purpose of Review This study aims to examine the treatments currently available for Tourette syndrome (TS) and to discuss evolving therapies, spanning behavioral, pharmacologic, complementary and alternative medicine, and neuromodulation approaches. Recent Findings Behavioral therapies have undergone several modifications to improve accessibility, including transitioning to a virtual format which is particularly important in the current pandemic. There are several recent or ongoing pharmacologic studies that have shown promise including the selective D1 receptor antagonist ecopipam and various cannabinoid compounds. Adaptive DBS may enable the physiologic markers of tics to determine stimulation parameters and improve tic outcomes related to neuromodulation. Summary In recent years, there has been a wealth of research across multiple treatment domains in the TS field. This review highlights exciting and new potential options for the future treatment of patients with TS.

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Deutetrabenazine in Tics Associated with Tourette Syndrome

Cited by 22 publications

References 27 publications

Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome

Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome

Safety and Efficacy of Flexible-Dose Deutetrabenazine in Children and Adolescents With Tourette Syndrome

Tourette Syndrome Treatment Updates: a Review and Discussion of the Current and Upcoming Literature

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