Adults with tardive dyskinesia who took valbenazine (Ingrezza) showed meaningful improvements in quality of life and daily functioning over 24 weeks, according to results from a phase 4 open-label study published in CNS Spectrums.
Study Design and Participants
The KINECT-PRO trial enrolled 59 adults with TD and at least mild TD-related distress, with underlying diagnoses including schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. At baseline, 41% had mild TD movement severity while 59% had moderate or severe TD.
Participants started on valbenazine 40 mg daily for 4 weeks, then received flexible dosing of 40, 60, or 80 mg through week 24. Of the 59 enrolled, 52 (88%) completed the week 24 visit.
Patient-Reported Outcomes
The primary endpoints measured changes from baseline to week 24 using three validated patient-reported outcomes: the Tardive Dyskinesia Impact Scale (TDIS), the EuroQoL Visual Analogue Scale (EQ-VAS), and the Sheehan Disability Scale (SDS).
In the efficacy population of 45 participants, mean TDIS scores improved 8.0 points, exceeding the scale’s minimal clinically important difference (MCID) of 4 points. AIMS total scores improved 6.8 points, surpassing its MCID of 2 points. EQ-VAS scores rose 13.1 points, and SDS social- and family-life scores decreased 2.3 and 1.6 points, respectively.
TDIS and AIMS improvements exceeded MCID thresholds as early as week 8 and week 4, respectively, and persisted through week 24. Approximately 58% of patients (26 of 45) met criteria for TD symptomatic remission at week 24, defined as an AIMS severity score of 0 or 1 across all 7 assessed body regions.
Even patients with milder baseline TD had clinically meaningful mean changes of -6.8 points on TDIS and -5.6 points on AIMS.
Safety Profile
Investigators reported no new safety signals. Adverse events were consistent with valbenazine’s known profile, which most commonly includes somnolence and sedation.
Valbenazine selectively inhibits the vesicular monoamine transporter 2 (VMAT2), reducing dopamine release without appreciable affinity for VMAT1 or dopaminergic, serotonergic, adrenergic, histaminergic, or muscarinic receptors. The FDA approved valbenazine for TD in adults in April 2017 based on the 6-week, randomized, double-blind, placebo-controlled KINECT 3 trial.
Clinical Implications
“Quality of life and day-to-day functioning are important considerations when evaluating the impact of tardive dyskinesia and treatment goals,” lead author Christoph U. Correll, MD, professor of psychiatry at Zucker Hillside Hospital, Northwell Health, said in a statement. “These findings showed improvements with INGREZZA in both clinician-rated movement severity and patient-reported daily impact and reinforced the potential for meaningful benefit across a broad range of patients regardless of baseline movement severity or underlying psychiatric diagnosis.”
TD is a movement disorder marked by involuntary, repetitive movements of the face, trunk, and limbs that typically emerges after prolonged exposure to antipsychotics and other dopamine receptor-blocking medications, including metoclopramide and prochlorperazine. The condition is estimated to affect at least 800,000 adults in the US and can be persistent and irreversible.
AIMS-based severity ratings have long anchored TD trials but capture little about the disorder’s effect on daily life—a gap TD-specific patient-reported measures have only recently begun to address. The TDIS used in KINECT-PRO was developed from qualitative research and KINECT 3/KINECT 4 trial data and underwent psychometric validation published in 2024.
The KINECT-PRO clinical study incorporated validated patient-reported measures to better understand the effects of treating tardive dyskinesia with valbenazine on patient-reported quality of life and functioning. “These findings add to the extensive body of evidence supporting the meaningful improvements INGREZZA has on movement severity and quality of life and functionality,” said Sanjay Keswani, MD, chief medical officer at Neurocrine Biosciences.