Sustained Benefits of Long-Term VMAT2 Inhibitor Therapy in Tardive Dyskinesia

EP: 1.Hidden in Plain Sight: Recognizing Signs and Symptoms of Tardive Dyskinesia

EP: 2.Understanding the Impact of Tardive Dyskinesia Across Patient Populations

EP: 3.The Role of VMAT2 Inhibitors in Tardive Dyskinesia

EP: 4.Movement Scores and Beyond: Patient-Reported Outcomes in Tardive Dyskinesia Management

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EP: 5.Sustained Benefits of Long-Term VMAT2 Inhibitor Therapy in Tardive Dyskinesia

EP: 6.Comparative Perspectives: TD Management vs Other Movement Disorders

Open-label extension studies for VMAT2 inhibitors provide important insights into their long-term use, safety, and sustained efficacy in treating tardive dyskinesia (TD). For example, the 3-year study on deutetrabenazine included over 300 patients, many of whom had psychotic or mood disorders. Throughout the study, deutetrabenazine maintained its effectiveness in reducing TD symptoms, with most patients continuing treatment. Similarly, the CONNECT 3 and CONNECT 4 studies with valbenazine pooled data from about 300 patients, including a significant number over age 65, showing that many stayed on treatment for up to 48 weeks. The continuation of treatment indicates that patients found the medication tolerable and beneficial to their quality of life.

Both studies reported adverse effects, with somnolence or sedation being the most common, particularly in older adults. Urinary tract infections were also noted but less frequent. Despite these adverse effects, many patients adapted their routines, such as avoiding driving or alcohol consumption while medicated, which helped them maintain treatment. Importantly, the rate of withdrawal from treatment was relatively low—about 28% in the deutetrabenazine study—suggesting that nearly three-quarters of patients chose to remain on therapy over time, signaling good overall tolerability and patient satisfaction.

While these open-label studies lack placebo controls and thus have limitations, the consistent patient retention and sustained symptom improvement offer promising evidence that VMAT2 inhibitors can be effective and tolerable for long-term management of TD. These data support the ongoing use of these medications, even in older populations, providing reassurance about their safety and the potential for meaningful, lasting benefits in everyday functioning.