Two vesicular monoamine transporter 2 (VMAT2) inhibitors, valbenazine and deutetrabenazine, are approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Since their initial approval in 2017, new formulations and doses for both medications have become available, including a sprinkle capsule for valbenazine and a once-daily tablet for deutetrabenazine. In light of these new therapeutic options, a comprehensive scoping review was conducted to consolidate the current knowledge about these medications. Both valbenazine and deutetrabenazine are safe and effective in treating TD. However, as they are different drugs, one objective of this review is to describe their pharmacology and pharmacokinetics. Another objective is to summarize the similarities and differences as to how these medications are prescribed, specifically in terms of their warnings and precautions, their use in special populations, and recommendations for dosing when taken with concomitant medications. Results from double-blind, placebo-controlled clinical trials are presented, along with post hoc analyses that provide benchmarks for clinical relevance (eg, effect size, number needed to treat, minimal clinically important difference). As most patients with TD will require ongoing treatment, findings from long-term studies provide evidence for the safety and effectiveness of these medications.

The crystal structure of valbenazine has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Valbenazine crystallizes in space group P212121 (#19) with a = 5.260267(17), b = 17.77028(7), c = 26.16427(9) Å, V = 2445.742(11) Å3, and Z = 4 at 295 K. The crystal structure consists of discrete molecules and the mean plane of the molecules is approximately (8,−2,15). There are no obvious strong intermolecular interactions. There is only one weak classical hydrogen bond in the structure, from the amino group to the ether oxygen atom. Two intramolecular and one intermolecular C–H⋯O hydrogen bonds also contribute to the lattice energy. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®)

There are several new and emerging medication interventions for both the acute and maintenance treatment phases of schizophrenia. Recently approved are 2 new dopamine receptor partial agonists, brexpiprazole and cariprazine, as well as 2 new long-acting injectable antipsychotic formulations, aripiprazole lauroxil and 3-month paliperidone palmitate. Although differences in efficacy compared to other available choices are not expected, the new oral options offer different tolerability profiles that may be attractive for individual patients who have had difficulties with older medications. The new long-acting injectable options provide additional flexibility in terms of increasing the time interval between injections. In Phase III of clinical development is a novel antipsychotic, lumateperone (ITI-007), that appears to have little in the way of significant adverse effects. Deutetrabenazine and valbenazine are agents in Phase III for the treatment of tardive dyskinesia, a condition that can be found among persons receiving chronic antipsychotic therapy. On the horizon are additional injectable formulations of familiar antipsychotics, aripiprazole and risperidone, that may be more convenient than what is presently available.