About the Author
Kayla Johnson, PharmD, BCPS, BCPP, is a clinical pharmacist specialist at Vanderbilt University Medical Center in Nashville, Tennessee.
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Pharmacy Practice in Focus: Health Systems
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VMAT2 inhibitors can improve movement symptoms.
Tardive dyskinesia (TD) is a heterogeneous, hyperkinetic movement disorder induced by dopamine-receptor blocking agents and is characterized by repetitive, involuntary movements that typically occur in the oral-buccal-lingual areas.1,2 Chronic blockade of D2 dopamine receptors from antipsychotics or other dopamine-blocking medications leads to potentially irreversible changes within the nigrostriatal dopamine pathway. These receptors become supersensitive or “upregulate” in an attempt to overcome drug-induced blockade in the striatum.3
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According to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition, Text Revision), the diagnosis of TD requires symptoms that develop after more than 3 months of cumulative exposure to antipsychotics or 1 month of exposure for adults older than 60 years.4 Additionally, symptoms must last at least 4 weeks.4 Occasionally, symptoms may also develop within 4 to 8 weeks after discontinuation of the offending agent.4 The Abnormal Involuntary Movement Scale (AIMS) is an assessment tool commonly used by clinicians to assist in diagnosing TD, along with the patient’s clinical history.1
Vesicular monoamine transporter type 2 (VMAT2) inhibitors are the only FDA-approved treatment options. At the American Association of Psychiatric Pharmacists 2025 Annual Meeting in Salt Lake City, Utah, Kayla Johnson, PharmD, BCPS, BCPP, presented on the management of TD with VMAT2 inhibitors in greater detail.
Updated in 2020, American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia (Third Edition) and A Modified Delphi Consensus Study of the Screening, Diagnosis, and Treatment of Tardive Dyskinesia recommend treatment with a VMAT2 inhibitor for patients with TD.1,5 Additionally, deutetrabenazine (Austedo; Teva Neuroscience, Inc) and valbenazine (Ingrezza; Neurocrine Biosciences, Inc) both carry a level A recommendation using the Scottish Intercollegiate Guidelines Network framework.6
A third VMAT2 inhibitor, tetrabenazine (Xenazine; Lundbeck Pharmaceuticals LLC), is also on the market but is only FDA approved for the treatment of Huntington disease (HD) chorea.7 These medications inhibit synaptic VMAT2, resulting in reversible depletion of neuroactive monoamines, such as dopamine, norepinephrine, and serotonin, to reduce involuntary, spontaneous movements.7 Based on a lack of head-to-head randomized clinical trials (RCTs), selection of the most appropriate VMAT2 inhibitor is routinely related to insurance approval, affordability, and patient-specific characteristics.
Although there are no head-to-head RCTs comparing VMAT2 inhibitors, indirect treatment comparisons (ITCs) and systematic reviews have been completed. Results from an ITC of deutetrabenazine and tetrabenazine in the treatment of HD chorea found that deutetrabenazine was associated with a lower risk of moderate to severe adverse events (AEs) and neuropsychiatric AEs in both adjusted and unadjusted analyses as well as a significantly lower rate of dose reduction or dose reduction/suspension in adjusted and unadjusted analyses.8 In an ITC of deutetrabenazine and valbenazine for the treatment of TD, the only statistically significant finding was greater improvement with valbenazine 80 mg daily at 6 weeks compared with deutetrabenazine 36 mg daily at 8 weeks.9
Clinical and economic outcomes associated with deutetrabenazine and valbenazine for the treatment of TD have also been compared. Ganz et al found that patients treated with valbenazine were more likely to have responded to treatment at 1 year, lived longer, and accrued more quality-adjusted life years. The incremental cost-effectiveness ratio was $9951 per quality-adjusted life year for valbenazine compared with deutetrabenazine. Drug acquisition costs were the largest contributor to total costs.10
Lastly, physicians, nurse practitioners, and physician assistants who prescribed valbenazine for TD within the past 24 months were asked to complete a web-based survey. The survey was used to elucidate clinician-reported improvement in symptoms and any noticeable changes in social or physical well-being in patients receiving VMAT2 inhibitors. Prior to treatment, 93% of patients showed impairment in 1 or more social domain and 88% in 1 or more physical domain. Following treatment, 80% to 95% showed improvement in social domains, 90% to 95% showed improvement in physical domains, and 73% showed improvement in their primary psychiatric condition. Most patients in the study were taking valbenazine (69%) compared with deutetrabenazine (28%) and tetrabenazine (3%).11
In addition to clinical trial data, treatment plan formulation should consider additional factors such as affordability, ease of use, efficacy, safety, and tolerability. Many options exist to help overcome affordability barriers such as co-pay cards for commercially insured patients, grant funds for patients with Medicare, and patient assistance programs for qualifying patients. Frequency of administration and pill burden also should be considered when choosing a VMAT2 inhibitor for treatment. Routine assessments of adherence and concurrent medication regimens to monitor for drug-drug interaction should occur because these may impact efficacy, safety, and tolerability of the chosen therapy. Additional safety monitoring should include electrocardiogram and liver function testing at baseline and as clinically indicated during treatment.
Kayla Johnson, PharmD, BCPS, BCPP, is a clinical pharmacist specialist at Vanderbilt University Medical Center in Nashville, Tennessee.
Due to the lack of head-to-head RCTs comparing VMAT2 inhibitors, unique aspects of each VMAT2 inhibitor lead to selection of therapy. In addition to VMAT2 inhibitor treatment leading to a reduction in AIMS score, it may also improve other patient outcomes such as social capabilities, physical capabilities, and primary psychiatric conditions.11 Finally, when formulating a VMAT2 inhibitor treatment plan, it is important to consider safety, tolerability, efficacy, and affordability.
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