Valbenazine induces global improvements and psychiatric stability in tardive dyskinesia
Presenter: Andrew Cutler, MD, SUNY Upstate Medical University, Syracuse, NY
Global improvements and psychiatric stability in adults with tardive dyskinesia: Post hoc analyses of two long-term valbenazine studies. Presented April 26, 2023.
In patients with tardive dyskinesia (TD) associated with long-term antipsychotic medications, treatment with once-daily valbenazine is effective for managing their TD symptoms without compromising their psychiatric stability, according to a post-hoc analysis of data from the KINECT 3 and KINECT 4 clinical trials presented by Andrew Cutler, MD, of SUNY Upstate Medical University, Syracuse, NY.
TD is a persistent, potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine blocking agents, Cutler said. Stopping or switching antipsychotic treatments to reduce TD can jeopardize a patient’s psychiatric stability. Effective TD treatment requires medications that improve TD symptoms without disruption of psychiatric stability. This can be especially challenging when patients have complex psychiatric conditions that require multiple medications.
The key clinical trials of valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor approved for TD, were conducted in patients with primary psychiatric disorders who were allowed to continue their psychiatric medications to maintain stability.
In this presentation, Cutler described results from a new study that assessed the efficacy of valbenazine on long-term TD improvements and psychiatric stability using post-hoc analyses from pooled data from the KINECT 3 and KINECT 4 clinical trials. In those trials, patients received valbenazine 40 or 80 mg once-daily for 48 weeks; concomitant medications needed to manage medical and psychiatric conditions were allowed. Outcomes were measured by psychiatric diagnosis of schizophrenia/schizoaffective disorder or mood disorder.
Of the 304 patients included in the analysis (mean age 57 years), 209 patients (68.8%) had schizophrenia/schizoaffective disorder and 95 patients (31.3%) had mood disorder. Baseline characteristics were generally similar between the two groups, Cutler said.
The percentages of patients who met the threshold for global response (rating of much improved or better) for the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC) were analyzed at week 48. Long-term global improvements were observed with valbenazine. More than 90% of all valbenazine-treated patients had a CGI-TD or PGIC rating of minimally improved or better at week 48, and more than 75% had robust improvements with CGI-TD or PGIC ratings of much improved or better.
Psychiatric stability was monitored in each subgroup. For schizophrenia/schizoaffective disorder, investigators used the Positive and Negative Syndrome Scale and Calgary Depression Scale for Depression; for mood disorder, they used the Young Mania Rating Scale and Montgomery Asberg Depression rating scale and Columbia-Suicide Severity Rating Scale. Mean changes from baseline to week 48 in the psychiatric symptom scale scores indicated maintenance of psychiatric stability in both subgroups.
“Pooled analyses from 2 48-week studies indicate that long-term treatment of TD with once-daily valbenazine (40 and 80 mg) resulted in substantial clinician-rated and patient-rated global improvements,” he said. “Global improvements were observed in patients who had a primary diagnosis of schizophrenia or schizoaffective disorder and in those with primary mood disorder. In addition, psychiatric stability was maintained long-term in both diagnosis subgroups.”
The results show that long-term treatment with once-daily valbenazine is effective for managing TD symptoms while maintaining patients’ well-being, he added.
References
Cutler A. Global improvements and psychiatric stability in adults with tardive dyskinesia: Post hoc analyses of two long-term valbenazine studies. Presented at the 75th Annual Meeting of the American Academy of Neurology, April 26, 2023.
Hauser RA, Meyer JM, Factor SA, et al. Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice. CNS Spectr 2022; 27(2):208-217. doi:10.1017/S109285292000200X. Epub 2020 Nov 20.
Bhidayasiri R, Jitkritsadakul O, Friedman JH, et al. Updating the recommendations for treatment of tardive syndromes: A systematic review of new evidence and practical treatment algorithm. J Neurol Sci 2018;389:67-75. doi:10.1016/j.jns.2018.02.010. Epub 2018 Feb 5.
Factor SA, Remington G, Comella CL, et al. The effects of valbenazine in participants with tardive dyskinesia: Results of the 1-Year KINECT 3 extension study. J Clin Psychiatry 2017; 78:1344-50. doi:10.4088/JCP.17m11777.
Marder SR, Singer C, Lindenmayer JP, et al. A phase 3, 1-year, open-label trial of valbenazine in adults with tardive dyskinesia. J Clin Psychopharmacol 2019; 39(6):620-627. doi:10.1097/JCP.0000000000001111.
Disclosures
Andrew Cutler has received personal compensation for serving as an employee and as an officer or member of the Board of Directors of Neuroscience Education Institute. He is a consultant for Alfasigma, Alkermes, Intra-Cellular Therapies, Lundbeck, MedAvante-ProPhase, Neurocrine Biosciences, Noven Pharmaceuticals, Otsuka Pharmaceuticals, Sage Therapeutics, Sunovion, Supernus, Teva Pharmaceuticals, AbbVie, Axsome Therapeutics, BioXcel, Boehringer Ingelheim, Cerevel, Corium, Karuna, Neumora, Relmada, and Janssen. He is on the speakers bureau for AbbVie, Alkermes, Intra-Cellular Therapies, Ironshore, Lundbeck, Neurocrine, Noven Pharmaceuticals, Otsuka Pharmaceuticals, Sunovion, Supernus, Teva Pharmaceuticals, Axsome Therapeutics, BioXcel, Corium, Janssen, and Tris Pharma, and he sits on the Scientific Advisory or Data Safety Monitoring board of COMPASS Pathways.