Long-Term Valbenazine Treatment Maximizes Benefits for Adults With Tardive Dyskinesia

Sustained treatment with once-daily valbenazine led to significant, long-lasting symptom improvement in adults with tardive dyskinesia (TD), according to an analysis presented at the 75th annual meeting of the American Academy of Neurology, in Boston, MA.

TD is a disorder characterized by persistent, involuntary movements of the face, torso, and extremities, which may also affect the respiratory muscles. Its pathogenesis has been linked to long-term treatment with dopamine receptor blockers, including antipsychotic agents. 

Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, has been approved for the treatment of TD in adults. Data from several double-blind, placebo-controlled trials and long-term phase 3 studies showed that valbenazine was effective in alleviating TD symptoms, generally tolerable, and had a positive safety profile [Hauser RA et al. Am J Psychiatry 2017;174(5):476-484]. A post-hoc analysis of results from the 48-week clinical trial KINECT 4 was conducted to assess treatment response in patients with TD who were treated with once-daily valbenazine for 48 weeks. The findings were presented on April 26 in a poster session (P 11.11-012). 

The study included adults aged 18 to 85 years who had received a diagnosis of neuroleptic-induced TD at least 3 months before the screening, and had a psychiatric diagnosis of schizophrenia, schizoaffective disorder, or mood disorder. Each participant was required to have a stable medical and psychiatric status, without significant risk for suicidal or violent behavior. Concomitant medications to treat the psychiatric and medical comorbidities were continued during the trial. 

All participants enrolled in KINECT 4 received valbenazine 40 mg once-daily for an initial period of 4 weeks. For those who tolerated the initial dose and received a clinical rating of “minimally improved” to “very much worse,” the daily dose was then increased to 80 mg. The 9 participants who did not tolerate the higher dose received a dose reduction (to 40 mg), while 74 participants continued taking 80 mg daily until week 48. Of 163 initial participants in KINECT 4, 103 (63%) were treatment completers and were included in the analysis. 

Improvements from baseline to week 8 (first study visit after the dose-optimization period) and week 48 (end of treatment) were assessed using the Abnormal Involuntary Movement Scale (AIMS) total score, as well as ratings of “much improved” or “very much improved” (score ≤2) on the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) and the Patient Global Impression of Change (PGIC). The analysis showed that the percentage of participants who achieved global improvements based on clinician assessments and patient self-reports increased over time. The proportion of those who met rigorous treatment response thresholds (≥70% AIMS improvement) surged from 17% to 52% between weeks 8 and 48. 

Moreover, most of the participants who did not experience major improvements in TD symptoms during the early phases reported ≥50% AIMS improvement by week 48 (81%). 

Robust improvements reflected in the CGI-TD (score ≤2) and PGIC (score ≤2) ratings were also recorded in a majority of participants (>80%) after 48 weeks of treatment with once-daily valbenazine. The proportion of participants who met these thresholds increased from week 8 to week 48 for both CGI-TD (from 50% to 92%) and PGIC (from 53% to 88%).

A large majority (86%) of participants who completed 48 weeks of treatment experienced significant, sustained improvements in TD (≥50% response threshold) with once-daily valbenazine, regardless of the dose used. 

“Overall, these results indicate that once-daily valbenazine can be a highly effective long-term treatment option in patients with TD,” the authors wrote. “Sustained treatment may be needed for some patients to achieve the full effects of valbenazine.”