Global Improvements and Psychiatric Stability in Adults with Tardive Dyskinesia and Mood Disorder: Post Hoc Analyses of Two Long-Term Valbenazine Studies

Abstract: Background: Effective and comprehensive treatment of tardive dyskinesia (TD) requires reducing patients’ abnormal involuntary movements while maintaining their psychiatric stability. In the long-term clinical trials of once-daily valbenazine, which is approved for TD, changes in psychiatric symptoms were assessed along with global improvements in TD. Methods: Post hoc analyses were conducted using data from participants in KINECT™-3 (NCT02274558) and KINECT™-4 (NCT02405091) who had a primary mood disorder and completed 48 weeks of treatment with valbenazine (40 or 80 mg). Two thresholds of response were defined, based on Week 48 scores for the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC): score ≤3 (“minimally improved” or better) and score ≤2 (“much improved” or better. The Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), and Columbia-Suicide Severity Rating Scale were used to monitor changes in psychiatric symptoms. Results: Ninety-five participants were included for analysis. Long-term global improvements were observed, with >95% of valbenazine-treated participants having a clinician-reported (CGI-TD=96.6%) or patient-reported (PGIC=96.6%) rating of “minimally improved” or better at Week 48. Moreover, >75% of participants had robust global improvements, as indicated by CGI-TD (77.6%) or PGIC (84.5%) ratings of “much improved” or better. Minimal changes in YMRS (-1.0) and MADRS (+0.3) total scores indicated psychiatric stability was maintained. Conclusion: Long-term treatment with once-daily valbenazine in participants with TD and a primary mood disorder resulted in substantial clinician- and self-reported global TD improvements, without compromising psychiatric stability.Short Description: In two long-term clinical trials (KINECT™-3, KINECT™-4), adults with tardive dyskinesia (TD) received once-daily valbenazine (40 or 80 mg) for 48 weeks. Data from these studies were pooled and analyzed in participants who had a primary mood disorder. Analyses based on clinician- and patient-reported measures indicated that these participants experienced substantial and sustained global improvements in TD with valbenazine. Moreover, mean changes in psychiatric symptom scales indicated maintenance of psychiatric stability throughout treatment.Name of Sponsoring Organization(s): This study was funded by Neurocrine Biosciences, Inc.