Tardive dyskinesia (TD) is a persistent and often disabling movement disorder that develops after prolonged exposure to dopamine receptor-blocking agents (DRBAs), including serotonin dopamine antagonists/partial agonists (SDA-PAs) and certain antiemetics. While these agents are essential for treating schizophrenia, bipolar disorder, and other psychiatric or gastrointestinal conditions, their chronic use can result in TD. Older adults are especially vulnerable to TD due to age-related changes in brain dopamine systems and reduced neural plasticity. Despite this heightened risk, elderly individuals have historically been underrepresented in clinical trials evaluating TD treatments, leaving clinicians with limited guidance for this population.

A new post hoc analysis published in the Journal of Clinical Psychiatry addresses this critical gap by evaluating the long-term effects of valbenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor that is FDA-approved for the treatment of TD, in adults aged 65 years and older. Researchers pooled data from two 48-week studies (the KINECT 3 extension and KINECT 4 open-label study), yielding a total of 304 participants, 55 of whom were aged 65 or older. Valbenazine was admistered at 40 or 80 mg daily and primary treatment outcomes were evaluated at weeks 8, 24, and 48.

Among the elderly subgroup, valbenazine demonstrated sustained and clinically meaningful improvements in TD symptoms. Mean AIMS total scores decreased by –8.8 points at Week 48, well above the threshold for minimal clinically important difference. By the end of treatment, 89.3% of elderly participants achieved at least a 30% improvement in Abnormal Involuntary Movement Scale (AIMS) score, and 82.1% achieved a 50% or greater reduction. These objective findings were mirrored by high rates of perceived improvement: 92.9% were rated as “much” or “very much improved” by clinicians (Clinical Global Impession of Change-TD, CGI-TD), and 85.7% self-reported meaningful improvement on the Patient Global Impression of Change (PGIC).

Valbenazine was generally well tolerated. The most frequently reported adverse events in the elderly group were urinary tract infections and somnolence (10.9% each). Although the discontinuation rate due to adverse events was higher in the elderly group (25.5% vs 13.3% in younger adults), no new safety signals emerged, and psychiatric symptom severity and extrapyramidal signs remained stable throughout the study.

These findings offer important reassurance that valbenazine is both effective and tolerable in older adults, who are among those most affected by TD. With once-daily dosing, no required titration, and no dose adjustments needed for age, valbenazine may represent a practical and much-needed therapeutic option for addressing TD in elderly patients.

Reference:

Sajatovic M et al. J Clin Psychiatry. 2025;86(2):24m15550. Abstract