VMAT2 Inhibitors in Neuropsychiatric Disorders
- PDF / 978,462 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 108 Downloads / 185 Views
REVIEW ARTICLE
VMAT2 Inhibitors in Neuropsychiatric Disorders Arjun Tarakad1 · Joohi Jimenez‑Shahed1 Published online: 10 October 2018 © Springer Nature Switzerland AG 2018
Abstract The basal ganglia and dopaminergic pathways play a central role in hyperkinetic movement disorders. Vesicular monoamine transporter 2 (VMAT2) inhibitors, which deplete dopamine at presynaptic striatal nerve terminals, are a class of drugs that have long been used to treat hyperkinetic movement disorders, but have recently gained more attention following their development for specific indications in the United States. At present, there are three commercially available VMAT2 inhibitors: tetrabenazine, deutetrabenazine, and valbenazine. Pharmacokinetics, metabolism, and dosing vary significantly between the three drugs, and likely underlie the more favorable side effect profile of the newer agents (deutetrabenazine and valbenazine). Tetrabenazine and deutetrabenazine have demonstrated safety and efficacy in the treatment of chorea associated with Huntington’s disease, including in randomized controlled trials, although direct comparison studies are limited. Both deutetrabenazine and valbenazine have demonstrated safety and efficacy in the treatment of tardive dyskinesia, with multiple double-blind, placebo-controlled trials, whereas tetrabenazine has been studied less rigorously. There have been no blinded, prospective trials with tetrabenazine in Tourette’s syndrome (TS); however, double-blind, placebo-controlled trials in TS are ongoing for both deutetrabenazine and valbenazine. Given the favored side effect profile of newer VMAT2 inhibitors, clinicians should be aware of the distinctions between agents and become familiar with differences in their use, especially as there is potential for their utilization to increase across the range of hyperkinetic movement disorders.
Key Points
1 Introduction
Recent development of new vesicular monoamine transporter 2 (VMAT2) inhibitors has led to broadened interest in their use for the treatment of hyperkinetic movement disorders.
Dopamine and the basal ganglia are thought to play a central role in the pathology of many abnormal movements associated with neuropsychiatric disorders. This makes the dopaminergic system a point of interest when targeting treatment of these movement disorders. Vesicular monoamine transporter 2 (VMAT2) inhibitors have proven particularly useful in the treatment of numerous hyperkinetic movement disorders, including Huntington’s disease (HD), tardive dyskinesia (TD), and Tourette’s syndrome (TS) [1]. While VMAT2 inhibitors have been used for treatment of such disorders for many years, and were available under a compassionate use, open-label protocol at a restricted number of centers for over 30 years [2], they have recently become more widely used and accessible following approvals for specific disorders in the United States (US), including HD and TD. The primary aim of this article is to describe the pharmacokinetics and review the clinical efficacy and safety prof
Data Loading...
