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Introduction : Significant need exists for effective, well-tolerated pharmacologic treatments for Tourette syndrome (TS). Medications that inhibit vesicular monoamine transporters (i.e. VMAT2 inhibitors) downregulate presynaptic packaging and release of dopamine into the neuronal synapse and are effective in treating hyperkinetic movement disorders such as Huntington's chorea and tardive dyskinesia (TD); thus, they may be useful in treating TS. Areas covered : This review describes the clinical program evaluating the safety and efficacy of valbenazine in the treatment of involuntary tics associated with TS in adult and pediatric subjects. While there was a trend in the 6 completed trials toward greater improvement in valbenazine-treated versus placebo subjects on the primary efficacy endpoint (Yale Global Tic Severity Scale Total Tic Score), this difference did not reach statistical significance. Valbenazine was generally well-tolerated in the studies, and treatment-emergent adverse events were consistent with valbenazine studies in TD. Expert opinion : Due to the failure to meet the primary endpoint in these trials, further investigation of valbenazine for TS is unlikely. Given the need for safe and effective TS therapies and the key role of VMAT2 in modulating dopaminergic activity, it is reasonable for future studies to investigate other VMAT2 inhibitors as potential treatments for TS.

Aims: To evaluate clinical and economic outcomes associated with valbenazine compared with deutetrabenazine in patients with tardive dyskinesia (TD) using a model that accounts for multiple dimensions of patient health status., Materials and Methods: A discretely integrated condition event model was developed to evaluate the cost-effectiveness of treatment with valbenazine and deutetrabenazine in a synthetic cohort of 1,000 patients with TD who were receiving antipsychotic medication to treat an underlying psychiatric disorder. Clinical inputs were derived from relevant clinical trials or from publicly available sources. Patients were assessed over 1 year using ≥50% improvement from baseline in Abnormal Involuntary Movement Scale (AIMS) total score as the primary definition of response. Response at 1 year using Clinical Global Impression of Change (CGIC) score ≤2 was also assessed. Health outcomes included quality-adjusted life years (QALYs), life years, proportion responding to treatment at 1 year, and number of psychiatric relapses., Results: Regardless of the definition used for response, patients treated with valbenazine were more likely to have responded to treatment at 1 year, lived longer, and accrued more QALYs than patients who received deutetrabenazine. Using the AIMS response criterion, the incremental cost-effectiveness ratio was $9,951/QALY for valbenazine compared with deutetrabenazine. By comparison, using the CGIC response criterion valbenazine dominated deutetrabenazine with valbenazine-treated patients accumulating more QALYs (3.4 vs 3.3 years) and incurring lower lifetime costs ($252,311 vs $283,208) than deutetrabenazine-treated patients., Limitations: There are no head-to-head trials of valbenazine and deutetrabenazine, so probabilities of response used in the model were calculated based on an indirect treatment comparison of results from individual trials with one drug or the other, using only those metrics reported across trials., Conclusions: In patients with TD, treatment with valbenazine is highly cost-effective compared with deutetrabenazine.

Introduction: Tardive dyskinesia (TD) is an iatrogenic movement disorder caused by exposure to dopamine receptor blocking agents. Two vesicular monoamine transporter type 2 (VMAT2) inhibitors for the treatment of TD were approved by the US Food and Drug Administration in 2017: valbenazine and deutetrabenazine. Areas covered: A brief review of TD and its identification, as well as a review of older treatment interventions is provided, followed by a detailed synthesis regarding the clinical utility of valbenazine and deutetrabenazine. Expert commentary: As evidenced from well-designed clinical trials, both valbenazine and deutetrabenazine are efficacious and tolerable. They differ in terms of labeled instructions for frequency of administration (twice daily for deutetrabenazine vs. once daily for valbenazine), titration requirements (dose to efficacy/tolerability for deutetrabenazine vs. titrate to target dose of 80 mg/day for valbenazine), need for food (administer deutetrabenazine with food), drug-drug interactions (consider CYP2D6 modulators for deutetrabenazine vs. both CYP2D6 and CYP3A4 for valbenazine), contraindications (hepatic impairment for deutetrabenazine), and minor differences in adverse event profile.

Introduction: Valbenazine is a selective VMAT2 inhibitor that the FDA approved in April 2017 for the specific treatment of tardive dyskinesia (TD), a movement disorder commonly caused by dopamine blocking agents. Valbenazine acts to decrease dopamine release, reducing excessive movement found in TD. Areas covered: This drug profile reviews the development of valbenazine and the clinical trials that led to its approval as the first treatment specific to TD. The literature search was performed with the PubMed online database. Expert commentary: Two clinical trials assessing the efficacy of valbenazine have shown the reduction of antipsychotic-induced involuntary movement. No life threatening adverse effects were found. Data from a 42-week extension study demonstrated sustained response.

Introduction: Chronic intake of typical neuroleptics or centrally acting dopamine receptor blocking antiemetics may cause onset of tardive syndromes. Various types exist. One of them is tardive dyskinesia, characterised by often stigmatising, purposeless, rapid, repetitive, stereotypic, involuntary movements of face, limbs or trunk. Effective symptomatic drug treatment options beyond application of tetrabenazine are rare. Tetrabenazine is usually administered three times daily due to the short half life of this agent. Areas covered: This narrative review discusses the value of valbenazine for the treatment of tardive dyskinesia as a therapeutic alternative to tetrabenazine. Expert commentary: Valbenazine is a selective inhibitor of vesicular monoamine transporter 2, which is metabolized to (+)-alpha-dihydrotetrabenazine. Valbenazine and particularly its metabolite inhibit vesicular monoamine transporter 2 function. Once daily intake of valbenazine ameliorated the severity of tardive dyskinesia. The chiral purity of valbenazine circumvents generation of the (-)alpha and (+) and (-)beta dihydrotetrabenazine metabolites of tetrabenazine or deutetrabenazine. Valbenazine and its metabolite do not antagonize postsynaptic monoamine receptors in contrast to the tetrabenazine formulations. Therefore one may hypothesize that fewer and less severe motor and psychopathological side effects will occur during valbenazine long term application compared with tetrabenazine or deutretrabenazine.