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.