An analysis of once-daily valbenazine trials revealed improvements in tardive dyskinesia, an involuntary movement disorder associated with antipsychotic use, according to study findings published in the Journal of Affective Disorders.
It has been established that first-generation antipsychotic use is sometimes accompanied by tardive dyskinesia, perhaps due to long-term exposure to dopamine receptor blocking agents. In 2017, the findings of a large meta-analysis indicated risk associated with not only first- but also second-generation antipsychotics, with prevalence rates of 30.0% and 20.7%, respectively.
Data were synthesized from two 6-week double-blind placebo-controlled studies (n=114) and a 48-week extension study (n=77) of valbenazine 40 or 80 mg/d. The demographics of these studies were comparable to other recent investigations of vesicular monoamine transporter 2 inhibitors for tardive dyskinesia. Patients were diagnosed with a bipolar or depressive disorder per the Diagnostic and Statistical Manual of Mental Disorders, 4th edition.
The researchers rated participants on the Abnormal Involuntary Movement Scale, the Clinical Global Impression of Change-Tardive Dyskinesia, and the Patient Global Impression of Change. Safety and tolerability were also assessed according to the Young Mania Rating Scale, the Montgomery-Åsberg Depression Rating Scale, and the report of any treatment-emergent adverse effects.
At week 6, participants in both the 40 mg/d and 80 mg/d groups showed significant improvements on the Abnormal Involuntary Movement Scale compared with placebo (40 mg/d, P <.01; 80 mg/d, P <.001). Clinical Global Impression of Change-Tardive Dyskinesia scores had also improved significantly at week 6, with Cohen’s D treatment effect sizes 0.73 (40 mg/d) and 0.80 (80 mg/d). There appeared to be some loss of treatment effect after washout in all 3 study groups, although the investigators were not able to identify why some patients experienced enduring clinical improvements and other patients did not.
In the 40 mg/d treatment group, 1 patient experienced treatment-emergent adverse effects and 2 discontinued treatment.
The primary limitation of the study was its post hoc nature; the studies analyzed were not specifically designed for patients with mood disorders. The investigators also cautioned that mood disorders themselves are an independent risk factor for tardive dyskinesia.
Investigators concluded “that once-daily treatment with valbenazine resulted in clinically meaningful [tardive dyskinesia] improvements in patients with bipolar disorder, [major depressive disorder], or other mood-related disorders.”
McIntyre R, Calabrese J, Nierenberg A, et al. The effects of valbenazine on tardive dyskinesia in patients with a primary mood disorder. J Affect Dis. 2018;246:217-223.