Benefits of Tardive Dyskinesia Treatment Need Not Come at the Expense of Psychiatric Stability

Long-term treatment with Valbenazine significantly reduced the severity of tardive dyskinesia (TD) symptoms without compromising mental stability in adults with TD and psychiatric comorbidities, according to research presented in a poster session (P11. 11-010) at the 75th annual meeting of the American Academy of Neurology, in Boston, MA. 

TD is a movement disorder associated with long-term exposure to dopamine receptor blocking agents, including antipsychotic medications. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V), TD persists despite discontinuation or change of the causative agents. 

“Effective and comprehensive TD treatment requires reducing patients’ abnormal involuntary movements without compromising their psychiatric stability,” the authors wrote. “This can be especially challenging when patients have complex psychiatric conditions that require multiple medications.” 

Olga Klepitskaya, MD, Associate Clinical Professor of Neurology at the University of Colorado School of Medicine, discussed results pooled from the KINECT 3 and KINECT 4 clinical trials, in which participants were treated with valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor approved for the treatment of adults with TD. The analysis was designed to evaluate global improvements and psychiatric status in patients with TD after long-term treatment.  

Patients enrolled in KINECT 3 and KINECT 4 received once-daily valbenazine (40 mg or 80 mg) for up to 48 weeks and were allowed to continue medications prescribed for comorbid medical and psychiatric conditions. Nearly 70% of the 304 included participants had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder, while the remainder were diagnosed with mood disorders. The patients shared similar baseline characteristics, regardless of psychiatric comorbidity. 

The Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC), with ratings of “minimally improved” or better (score ≤3) and “much improved” or “very much improved” (score ≤2), were used as response thresholds to measure global improvements in TD symptoms. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) for participants diagnosed with schizophrenia or schizoaffective disorder, and the Young Mania Rating Scale (YMRS) and the Montgomery-Åsberg Depression Rating Scale (MADRS) for those with mood disorders. The Columbia-Suicide Severity Rating Scale was used to assess suicidality in all participants.

A large majority of the participants who completed 48 weeks of treatment had long-term clinician- and patient-rated global improvements in TD symptoms. More than 90% had a rating of “minimally improved” or better and more than 75% had robust improvements by week 48, reflected in ratings of “much improved” or better. The authors noted that these benefits were achieved without compromising patients’ psychiatric stability. Psychiatric symptom scores showed that mental stability was maintained throughout the valbenazine treatment period. No participants developed suicidal ideation or behavior. 

“Long-term treatment with once-daily valbenazine is effective for managing TD symptoms while maintaining patients’ mental wellbeing,” the authors concluded.