Effects of Concomitant Medication Use on Tardive Dyskinesia Outcomes in Long-Term Valbenazine Trials

Background: Patients with tardive dyskinesia (TD) often take multiple concomitant medications for psychiatric comorbidities. Data from long-term valbenazine trials were analyzed to evaluate the effects of concomitant medications on treatment outcomes.
Methods: Data were pooled from two phase 3 trials, KINECT 3 (NCT02274558) and KINECT 4 (NCT02405091), in which participants received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Outcomes included Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7) mean change from baseline (CFB) to Wk48 and AIMS response (≥50% total score improvement). Concomitant medication subgroups were defined as: antipsychotic (yes, no); antipsychotic type (atypical only, typical or both [typical+atypical]); antidepressant (yes, no); anxiolytic (benzodiazepines+others: yes, no); anticholinergic (yes, no). Subgroup categories were not mutually exclusive.
Results: Of 304 participants, 85.5% were taking antipsychotics, 64.5% antidepressants, 30.3% anxiolytics, and 32.2% anticholinergics. Mean AIMS total score CFB was significant in all subgroups (P<0.05 versus baseline): antipsychotic (yes, -7.6; no,  -8.0), antipsychotic type (atypical only, -7.9; typical or both, -5.8); antidepressant (yes, -8.3; no, -6.3); anxiolytic (yes, -8.4; no, -7.3); anticholinergic (yes, -6.1; no, -8.3). There was a greater proportion of AIMS responders for all “yes” compared to “no” subgroups, except for anticholinergics (antipsychotics: yes, 68.9%; no, 53.6%; antidepressants: yes, 70.5%; no, 57.9%; anxiolytics: yes, 72.4%; no, 63.6%; anticholinergics: yes, 51.9%; no, 72.4%).
Conclusion: Results from long-term valbenazine trials indicate sustained TD improvements in patients taking concomitant antipsychotics, antidepressants, anxiolytics, and/or anticholinergics, although concomitant use of anticholinergics was associated with a lower proportion of AIMS responders.