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eCase: Use of Valbenazine in an Older Patient With Tardive Dyskinesia

Rebecca S. Roma, MD
Released: August 31, 2021
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Key Research

TD Prevalence and Risks
TD, a movement disorder characterized by uncontrollable, abnormal, and repetitive movements of the face, torso, and/or other body parts, is associated with exposure to dopamine receptor–blocking agents, including antipsychotics. Risk factors include older age, female sex, type of antipsychotic agents and routes of administration, preexisting movement disorders, and general health of the patient.1,2 TD prevalence among patients receiving antipsychotics is approximately 20% to 30%, and higher among older patients.2 Contrary to expectations, introduction of second-generation antipsychotics has not eliminated TD risk and the difference in TD incidence between the first-generation (typical) antipsychotics (FGA) and second-generation antipsychotics is 5.5% vs 3.9%, respectively, suggesting that the incidence and prevalence of TD is relatively unchanged since the 1980s.3 Since discontinuation of treatment deteriorates and exacerbates psychotic symptoms and mental condition, there is little evidence that this is an effective approach for TD treatment. Furthermore, other medication classes have a high TD prevalence and there is a lack of awareness about their TD-inducing effects in clinical practice.4

Impact of age on the body and brain is an important factor in TD, and therefore, older patients have a 3.2-folder higher risk of developing medication-induced TD.5 Drug-induced TD is also higher in women (30% incidence rate). Antidepressant-induced TD is common in older patients with comorbid conditions, and age-related changes in the absorption, distribution, metabolism, and excretion of medications may lead to increased medication accumulation and more severe adverse events in these patients. Moreover, TD symptoms are dose dependent and exacerbated in individuals who have previously been administered lithium.7

TD Assessment and Screening
Monitoring and recognizing TD are critical skills for healthcare professionals who prescribe medications that can increase TD risks or exacerbate TD symptoms. AIMS is considered the gold standard to measure the severity of abnormal movements in TD, but diagnosis requires thorough evaluation of patient’s clinical presentation, ruling out other diagnostic possibilities, and review of medication history. Regular monitoring using AIMS is recommended to be conducted every 3-6 months for early recognition, although the AIMS is underused.8,9

The objective assessment of patients’ movements such as their location/severity is valuable, but it is important to assess the impact of TD on patients’ mood, self-image, and behaviors and evaluate if the TD is interfering with social and occupational functioning. Early studies indicate that patients denied awareness of TD symptoms, which can contribute to delayed diagnosis and treatment. Although guidelines for TD screening recommend assessment every 3 or 6 months for high-risk patients, experts recommend screening at every clinical encounter to lower delayed diagnosis of early TD cases. Before discussing TD treatment with patients, it is essential to consider differential diagnosis of other movement disorders that may require very different management and are also common in older patients. TD symptoms can be misdiagnosed as drug-induced parkinsonism, and treatments for parkinsonism worsens TD symptoms.9

TD Treatment Options
Several treatment options for TD have been evaluated including amantadine, propranolol, piracetam, levetiracetam, acetazolamide, bromocriptine, thiamine, zolpidem, vitamin E, vitamin B6, calcium channel blockers, selegiline, Gingko biloba, melatonin, buspirone, botulinum toxin type A, electroconvulsive therapy, switching to clozapine and dopamine, but there is insufficient evidence to support efficacy in TD treatment.10 Recent advances in TD pharmacologic research and pathophysiology have identified molecular pathways and genetic components involved. TD is hypothesized to be caused by postsynaptic dopamine receptor hypersensitivity that leads to synaptic plasticity. VMAT2 was identified as a genetic marker in TD and is responsible for monoamine transport across synaptic vesicle for degradation. Inhibiting VMAT2 interrupts monoamine transport and degradation causing monoamine depletion in the synaptic pool. These studies collectively pointed toward VMAT2 inhibition as a new avenue for TD treatment.11

Valbenazine, a highly selective VMAT2 inhibitor, was the first of this class to be approved by the FDA for TD treatment and was followed by a second VMAT2 inhibitor, deutetrabenazine, for the treatment of TD.11 Clinical trials of valbenazine have demonstrated excellent tolerability and a favorable pharmacokinetic profile with once-daily dosing. In clinical trials, the common adverse events, such as sedation, headache, and urinary tract infections, did not lead to discontinuation of the medication.12


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