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Tardive Dyskinesia Research Review
  • CME
  • CE

Sanjay Gupta, MD
Joseph P. McEvoy, MD
Released: August 31, 2021

The effects of valbenazine on tardive dyskinesia in older and younger patients

Sajatovic, et al. Int J Geriatr Psychiatry. 2020;35:69-79.

Background
This study used pooled data from clinical trial outcomes to evaluate the effects of once-daily valbenazine (40 or 80 mg/day) in older and younger adults with tardive dyskinesia (TD).

Methods
Data were pooled from the valbenazine clinical trials. These included three 6-week, randomized, double-blind, placebo-controlled studies (KINECT, KINECT 2, and KINECT 3) and 2 long-term studies (KINECT 3 extension and KINECT 4).

The authors compared outcomes in older and younger participants (aged 55 years or older and younger than 55 years, respectively) including Abnormal Involuntary Movement Scale (AIMS) response (threshold of ≥50% improvement from baseline in total score [items 1-7]) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) response (score ≤2 [“very much improved” or “much improved”]).

Safety assessments included treatment-emergent adverse events.

Results
At Week 6, the percentage of participants who met the AIMS response threshold was higher with valbenazine vs placebo in both subgroups (aged 55 years or older, 80 mg/day: 39.7%; 40 mg/day: 28.6%; placebo: 9.7%; and younger than 55 years of age, 80 mg/day: 39.5%; 40 mg/day: 20.0%; placebo: 10.8%). The percentage of participants with CGI-TD response was also higher with valbenazine vs placebo (aged 55 years or older, 80 mg/day: 41.3%; 40 mg/day: 30.2%; placebo: 19.4%; and younger than 55 years of age, 80 mg/day: 39.5%; 40 mg/day: 35.3%; placebo: 18.5%). Responses at Week 48 (end of long-term treatment, combined doses) were as follows: For patients 55 years of age or older AIMS was 70.7% and CGI-TD was 82.8%, and for patients younger than 55 years of age, AIMS was 58.7% and CGI-TD was 72.3%.

No significant differences between older and younger subgroups were found for AIMS or CGI-TD response.

No new safety signals or treatment-emergent adverse events of clinical concern were found in older participants who received long-term treatment.

Conclusions:
Valbenazine improved TD and was generally well tolerated in both older and younger adults.

Clinical Commentary (Joseph P. McEvoy, MD)
The authors combined the premarketing clinical trials submitted for FDA approval of valbenazine, allowing more power to examine the questions of differential efficacy or tolerability between patients younger than 55 years of age and 55 years of age or older.

Clinical Insights

  • Both groups demonstrated the efficacy of valbenazine and to an equivalent degree.
  • Both groups also evidenced excellent tolerability.
  • Compared with a previous study (Thai-Cuarto, et al. Drug Safety. 2018;41:429-440), the larger sample size of this analysis, which combined premarketing trial populations, did not reveal any cardiovascular risks that could have been missed by analyzing each clinical trial individually.

Summary
Previous studies evaluating postmarketing trial data with valbenazine supports its efficacy and tolerability without any suggestion of declining efficacy or tolerability with age, and an absence of any clinically concerning pattern of cardiovascular effects. In this study, the larger sample size, created by combining similar data sets, increased the potential to detect minor differences, differences by intrinsic characteristics (eg, age), or rare events. The larger sample sizes in these analyses did not find different patterns of therapeutic response by age or any hint of cardiovascular risk.

Clinical Commentary (Sanjay Gupta, MD)
This is a valuable analysis from the healthcare professional’s perspective.Increasing age is one of the risk factors for TD.Increasing age also results in pharmacokinetic changes. Even though this was not a prospective study, its findings carry significant value for the use of VMAT2 inhibitors (valbenazine in this case) for the treatment of TD in older adults. The age cut-off of 55 years is consistent with the literature. A prospective study certainly would be ideal, which I doubt would ever get done for multiple reasons.

Clinical Insights

  • There are no age-related differences in efficacy and tolerability between older and younger adults. Hence, valbenazine can be prescribed similarly in older adults and there are no nuances related to tolerability.
  • The presence of these data increase the comfort level for the prescription of valbenazine in older adults.

Summary
From the perspective of a healthcare professionals, the primary goal is to screen and treat as well as monitor for treatment-emergent adverse events similarly in both younger and older adults. We should be careful committing an older adult to antipsychotic therapy (only when indicated) and know that TD can occur with just 1 month of therapy, particularly since advanced age is a TD risk factor.

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