Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders

Abstract

Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research.

Decreased Gray Matter Volume of Cuneus and Lingual Gyrus in Schizophrenia Patients with Tardive Dyskinesia is Associated with Abnormal Involuntary Movement

“…TD reduces quality of life and disrupts a patient’s personal, social, and professional function 7 . A recent report showed that the annualized incidence of TD was 5.5% in patients treated with first-generation antipsychotics, and 3.5% in those treated with second-generation antipsychotics 8 , 9 . The incidence of TD with atypical antipsychotics is higher than expected, and underscores the fact that TD remains a significant clinical problem 10 .…”

Candidate genes involved in the development of antipsychotic-induced tardive dyskinesia in patients with schizophrenia

“…Исследования, изучающие ОНВ 609C>T, показали, что аллель T связан с более высоким риском развития АП-индуцированной ТД и более высокими показателями шкалы AIMS в корейской популяции, однако в китайской популяции таких данных не было получено. Это может быть связано с различиями в частоте аллелей в разных этнических группах [32].…”

Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia

“…Tardive dyskinesia (TD) is a movement disorder caused by dopamine-receptor antagonists (DRAs), such as typical and atypical antipsychotics and antiemetics, including metoclopramide and prochlorperazine 1–7. The uncontrolled abnormal movements of TD can be socially stigmatising, disabling and worsen quality of life 8–10. Clinicians may initially attempt to manage TD by lowering the dose of or discontinuing the causative agent, but this may not be possible, as it could exacerbate symptoms of the existing primary psychiatric disease or worsen TD symptoms 1–3 5…”