Pathophysiology, prognosis and treatment of tardive dyskinesia

Abstract

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)

Evaluation of antipsychotic monitoring in a community health center during the COVID‐19 pandemic

“…1 All patients on antipsychotics require frequent metabolic and movement disorder monitoring to ensure proper disease and adverse drug reaction management, regardless of age, race, diagnosis, antipsychotic used, or dose. 2,3 Proper monitoring can increase the quality of life, ensure proper disease management, and decrease morbidity and mortality. According to the American Psychiatric Association (APA) Practice Guidelines for the Treatment of Patients with Schizophrenia and use of antipsychotics, 4 monitoring parameters should include glucose, hemoglobin A1C (Hgb A1C), lipids, weight, body mass index (BMI), waist circumference, and movement disorder testing for extrapyramidal syndromes (EPS).…”

“…In the United States alone, over 4 million adults are currently on antipsychotic medications 1 . All patients on antipsychotics require frequent metabolic and movement disorder monitoring to ensure proper disease and adverse drug reaction management, regardless of age, race, diagnosis, antipsychotic used, or dose 2,3 . Proper monitoring can increase the quality of life, ensure proper disease management, and decrease morbidity and mortality.…”

Neurological Perspectives Should Be Integrated Into the Management of Tardive Dyskinesia—Expert Opinions and Proposed Educational Initiatives in Asia

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227Tardive dyskinesia(TD) is a movement disorder that exhibits a range of clinical manifestations arising as side effects of treatment with dopamine receptor-blocking agents, primarily antipsychotic drugs (APDs) [1,2].Consequently,its management overlaps different disciplines, in particular, psychiatry and neurology.In practice, this canresult ina gap in management whereby patients receive only one aspect of what should ideally bemultidisciplinarycare. Psychiatrists will naturally focus on controllingthe patient'schallenging psychotic symptomsand may not be specialized in the evaluation of the abnormal movements that are a core manifestation of TD [3,4].As a result, exposure of neurologists to TD patients may be limited to when the condition has becomesevere.

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The interplay of psychopharmacology and medical conditions

“…Therefore, it is currently unclear whether these abnormalities are non-specific factors common to many disorders or whether they have a specific pathogenetic role. The influence of treatments is also unclear, although treatments are usually considered useful in reducing oxidative stress (Lepping et al , 2011; Dietrich-Muszalska et al , 2021; Mariani et al , 2022), the opposite has also been reported, at least in some body tissues (Kropp et al , 2005; Dietrich-Muszalska and Kolińska-Łukaszuk, 2018; Todorović Vukotić et al , 2021). The paper by Yazla (Yazla et al , 2023) in this issue reports an interesting analysis of oxidative stress parameters and serum prolidase enzymatic activity, an enzyme usually associated with oxidative stress.…”

“…Tardive dyskinesia is now less of a concern due to the reduced risk posed by newer antipsychotics, but it is still present and therefore treatments are needed. Besides clozapine, there is some evidence for other treatments such as deutetrabenazine, pyridoxine, melatonin and repetitive transcranial magnetic stimulation (Taylor et al, 2021;Takeuchi et al, 2022). The recently approved valbenazine, with its innovative mechanism of action, is a significant improvement.…”