Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice.

Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers. Misdiagnosis can lead to incorrect interventions with suboptimal or even deleterious results. To aid in the identification and differentiation of TD in the psychiatric practice setting, we review its clinical features and movement phenomenology, as well as those of other antipsychotic-induced movement disorders, with accompanying links to illustrative videos. Exposure to dopamine receptor blocking agents (DRBAs) such as antipsychotics or antiemetics is associated with a spectrum of movement disorders including TD. The differential diagnosis of TD is based on history of DRBA exposure, recent discontinuation or dose reduction of a DRBA, and movement phenomenology. Common diagnostic challenges are the abnormal behaviors and dyskinesias associated with advanced age or chronic mental illness, and other movement disorders associated with DRBA therapy, such as akathisia, parkinsonian tremor, and tremor related to use of mood stabilizing agents (eg, lithium, divalproex). Duration of exposure may help rule out acute drug-induced syndromes such as acute dystonia or acute/subacute akathisia. Another important consideration is the potential for TD to present together with other drug-induced movement disorders (eg, parkinsonism, parkinsonian tremor, and postural tremor from mood stabilizers) in the same patient, which can complicate both diagnosis and management. After documentation of the phenomenology, severity, and distribution of TD movements, treatment options should be reviewed with the patient and caregivers.

Tardive Dyskinesia: Treatment Update.

PURPOSE OF REVIEW: Tardive dyskinesia (TD) is caused by exposure to medications with dopamine antagonism, mainly antipsychotics. It often distresses individuals, physically and emotionally and affects their quality of life. We evaluated peer-reviewed recently published articles with a goal of providing a critically appraised update on the latest advancements in this field. RECENT FINDINGS: In 2017, FDA approved VMAT2 inhibitors, deutetrabenazine and valbenazine. They have demonstrated efficacy in several class 1 studies. Also there have been update in the evidence-based guidelines for treatment for tardive dyskinesia. Various medication classes are being used for treatment of TD with VMAT2 inhibitors to be first FDA-approved medications. Their use should be tailored to the individual patient. Long-term studies will further guide us in how to optimize treatment, especially in the real-world setting. As clinicians, we need to take into consideration all aspects of symptomatology, etiology, potential side effects of the medications, to find the best possible "match" for our patients.

Clinical Utility of Deutetrabenazine as a Treatment Option for Chorea Associated with Huntington's Disease and Tardive Dyskinesia.

Deutetrabenazine (DTBZ) is used for the treatment of tardive dyskinesia (TD) and chorea in Huntington's Disease (HD). Four pivotal clinical trials showed the efficacy of DTBZ in these conditions. Long term follow-up studies confirmed evidence of overall safety and continued efficacy of this drug. Indirect comparisons revealed relative superiority of DTBZ over TBZ in terms of safety, but direct comparisons of safety and efficacy between the VMAT2 and dopamine blocking agents is lacking. Deutetrabenazine is safe and effective in the treatment of TD and chorea in HD in doses up to 72 mg daily and for up to three years in duration.

Pathophysiology, prognosis and treatment of tardive dyskinesia.

Tardive dyskinesia (TD), a movement disorder associated with antipsychotics, most frequently affects the lower face and jaw muscles, but can also affect walking, breathing and use of the hands and limbs. Knowledge of TD among physicians may be limited, and the pathophysiology of TD is poorly understood. We conducted this review to summarise the current knowledge surrounding the pathophysiology of TD and present recommendations for prevention and treatment based on a literature search and roundtable discussion attended by psychiatrists in Japan. It has been suggested that dopamine hypersensitivity, damaged gamma-aminobutyric acidergic neurons and/or increased production of reactive oxygen species may contribute to development of TD. Symptoms can profoundly affect everyday life; patients who develop TD have poorer prognoses, worse health-related quality of life, greater social withdrawal and higher mortality than patients without TD. Traditional treatment options include dietary supplements, although evidence for their effectiveness is low. Among pharmaceutical interventions, there is moderate evidence that switching to the second-generation antipsychotic clozapine, which has a lower affinity for dopamine D2 receptors than other antipsychotics, may improve symptoms. Vesicular monoamine transporter 2 (VMAT-2) inhibitors, which oppose the increased dopaminergic activity associated with prolonged antipsychotic use by interfering with dopamine uptake and storage, have the strongest evidence for efficacy. VMAT-2 inhibitors are approved in the United States for the treatment of TD, and the first VMAT-2 inhibitor was approved in Japan for this indication in March 2022. Most guidelines recommend treating TD by first reducing the dose of antipsychotics or switching to clozapine or other second-generation antipsychotics, which have a lower association with TD than first-generation antipsychotics. We recommend focusing on prevention and monitoring for TD when prescribing antipsychotics, given that TD is often irreversible. Physicians should treat with antipsychotics only when necessary and at the lowest effective dose, and frequently monitor for TD symptoms. Plain Language Summary: Plain Language Summary (In Japanese). Visual Summary: Visual Summary (In Japanese).

Cost-effectiveness of valbenazine compared with deutetrabenazine for the treatment of tardive dyskinesia.

AIMS: To evaluate clinical and economic outcomes associated with valbenazine compared with deutetrabenazine in patients with tardive dyskinesia (TD) using a model that accounts for multiple dimensions of patient health status. MATERIALS AND METHODS: A discretely integrated condition event model was developed to evaluate the cost-effectiveness of treatment with valbenazine and deutetrabenazine in a synthetic cohort of 1,000 patients with TD who were receiving antipsychotic medication to treat an underlying psychiatric disorder. Clinical inputs were derived from relevant clinical trials or from publicly available sources. Patients were assessed over 1 year using ≥50% improvement from baseline in Abnormal Involuntary Movement Scale (AIMS) total score as the primary definition of response. Response at 1 year using Clinical Global Impression of Change (CGIC) score ≤2 was also assessed. Health outcomes included quality-adjusted life years (QALYs), life years, proportion responding to treatment at 1 year, and number of psychiatric relapses. RESULTS: Regardless of the definition used for response, patients treated with valbenazine were more likely to have responded to treatment at 1 year, lived longer, and accrued more QALYs than patients who received deutetrabenazine. Using the AIMS response criterion, the incremental cost-effectiveness ratio was $9,951/QALY for valbenazine compared with deutetrabenazine. By comparison, using the CGIC response criterion valbenazine dominated deutetrabenazine with valbenazine-treated patients accumulating more QALYs (3.4 vs 3.3 years) and incurring lower lifetime costs ($252,311 vs $283,208) than deutetrabenazine-treated patients. LIMITATIONS: There are no head-to-head trials of valbenazine and deutetrabenazine, so probabilities of response used in the model were calculated based on an indirect treatment comparison of results from individual trials with one drug or the other, using only those metrics reported across trials. CONCLUSIONS: In patients with TD, treatment with valbenazine is highly cost-effective compared with deutetrabenazine.

A Brief Review on the Role of Vesicular Monoamine Transporter2 Inhibitors in Hyperkinetic Movement Disorders.

Hyperkinetic movement disorders are a common group of movement abnormalities in children, characterized with repetitive unintended involuntary movements. Major hyperkinetic movements include tremor, tic, dystonia, myoclonus, and chorea. Although a number of drugs have been proven to be beneficial for these abnormalities, some patients may become resistant to conventional treatments. Vesicular monoamine transporter2 (VMAT2) inhibitors (Tetrabenazine, Deutetrabenazine, and Valbenazine) are new agents introduced in the last decade for treating some of movement disorders, in particular tardive dyskinesia, Huntington chorea, and Tourette syndrome. In this brief review, we discussed the role of these drugs in managing hyperkinetic movement disorders.

Treatment of Tardive Dyskinesia.

Tardive dyskinesia (TD) is an iatrogenic condition that encompasses a wide phenomenological spectrum of movement disorders caused by exposure to dopamine receptor blocking agents (DRBAs). TD may cause troublesome or disabling symptoms that impair quality of life. Due to frequent, often inappropriate, use of DRBAs, TD prevalence rates among patients exposed to DRBAs continue to be high. The judicious use of DRBAs is key to the prevention of TD, reduction of disease burden, and achieving lasting remission. Dopamine-depleting vesicular monoamine transporter type 2 inhibitors are considered the treatment of choice of TD.

Management of Tardive Syndrome: Medications and Surgical Treatments.

Tardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement (orobuccolingual stereotypy, dystonia, tics, and others) and nonmotor features (akathisia and pain). TS has garnered increased attention of late because of the Food and Drug Administration approval of the first therapeutic agents developed specifically for this purpose. This paper will begin with a discussion on pathogenesis, clinical features, and epidemiology. However, the main focus will be treatment options currently available for TS including a suggested algorithm based on current evidence. Recently, there have been significant advances in TS therapy, particularly with the development of 2 new vesicular monoamine transporter type 2 inhibitors for TS and with new data on the efficacy of deep brain stimulation. The discussion will start with switching antipsychotics and the use of clozapine monotherapy which, despite the lack of higher-level evidence, should be considered for the treatment of psychosis and TS. Anti-dyskinetic drugs are separated into 3 tiers: 1) vesicular monoamine transporter type 2 inhibitors, which have level A evidence, are approved for use in TS and are recommended first-choice agents; 2) drugs with lower level of evidence for efficacy including clonazepam, Ginkgo biloba, and amantadine; and 3) drugs that have the potential to be beneficial, but currently have insufficient evidence including levetiracetam, piracetam, vitamin B6, melatonin, baclofen, propranolol, zolpidem, and zonisamide. Finally, the roles of botulinum toxin and surgical therapy will be examined. Current therapies, though improved, are symptomatic. Next steps should focus on the prevention and reversal of the pathogenic process.

Role of Vesicular Monoamine Transporter 2 Inhibitors in Tardive Dyskinesia Management.

Tardive dyskinesia (TD) is a distressing and disabling movement disorder that occurs with the use of chronic neuroleptic medications. TD is defined as involuntary athetoid or choreiform movements of head, trunk or limbs. Tongue, lower face, jaw, and extremities are commonly involved but pharyngeal, diaphragmatic, or truncal muscles are also sometimes involved affecting breathing, swallowing, speech, posture, gait, and mobility of an individual. TD is a debilitating movement disorder that requires timely intervention. Subtle tongue movements, tic-like facial movements or increased blink frequency could be some of the initial manifestations of TD. Our article is focused on the new advents in treating TD, their efficacy, and tolerability with emphasizing their side effect profile. The implication of a genetic marker vesicular monoamine transporter 2 (VMAT2), helped in investigating VMAT2 inhibitors for alleviating TD. Among the modalities tested, only VMAT2 inhibitors reported efficacy. However, the outcome of long-term use and its side effect profile can only be determined with longer studies utilizing large set data. More clinical trials are required to explore individual drug efficacy and their long-term adverse effects. We aim to provide an overview of TD management, illustrating the priority of VMAT2 inhibitors and to determine the importance of selecting an optimal medication. A search through PubMed with terms "Tardive dyskinesia" and "VMAT2 inhibitors" was carried out. Several treatment modalities were tested to control the symptoms of TD with limited benefit. However, VMAT2 inhibitors showed improvement in the Abnormal Involuntary Movement Scale (AIMS) rating scale for TD. Valbenazine and deutetrabenazine (d-TBZ) were recently approved by the Food and Drug Administration (FDA) for treating TD in adults.

VMAT2 inhibitors for the treatment of tardive dyskinesia.

Tardive dyskinesia (TD) is an often disabling hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Although initially thought to most commonly occur with typical antipsychotics, the incidence is likely similar with atypical antipsychotics and antiemetics such as metoclopramide. Increased prescribing of these agents as well as low rates of remission have contributed to a rising prevalence of TD. Although this condition was described nearly 60 years ago, it is only within the past year that two novel therapeutic agents were FDA approved. Characterization of the VMAT2 inhibitor tetrabenazine, which was identified as a therapeutic agent for TD in older clinical trials, has yielded two distinct pharmacologic strategies to optimize response. The first strategy, used to create deutetrabenazine, employed deuterization of tetrabenazine to stabilize the pharmacokinetics and eliminate high peak plasma levels. The second strategy was the creation of a prodrug, valbenazine, for the two most active isoforms of tetrabenazine that also resulted in more stable pharmacokinetics and eliminated peak plasma levels. Both agents have been demonstrated to be effective and safe for the treatment of TD in multicenter, controlled trials and their development has led to a resurgence of interest in the characterization and treatment of this movement disorder.