The Association Study of Polymorphisms in DAT, DRD2, and COMT Genes and Acute Extrapyramidal Adverse Effects in Male Schizophrenic Patients Treated With Haloperidol

Abstract

Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The development of acute EPSs could depend on the activity of dopaminergic system and its gene variants. The aim of this study was to determine the association between dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O-methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2 weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were determined. Extrapyramidal symptoms occurred in 116 (48.3%) of patients. Statistically significant associations were found for SLC6A3 VNTR and COMT Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10 genotype had almost twice the odds to develop EPSs compared with those with all other SLC6A3 genotypes (odds ratio, 1.9; 95% confidence interval, 1.13-3.30), and patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs than those with all other COMT genotypes (odds ratio, 1.7; 95% confidence interval, 1.01-2.88). There was no statistically significant association between genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the development of particular EPSs.In conclusion, the results of the present study showed for the first time the association between acute haloperidol-induced EPSs and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological mechanisms underlying these findings are not yet understood, the results suggest that the dopaminergic gene variations could predict the vulnerability to the development of the acute EPSs in haloperidol-treated schizophrenic patients.

Safety and efficacy of commonly used antiemetics

“…Cardiovascular effects other than QTc have also been noted with droperidol administration, including hypotension and tachycardia [64]. Droperidol should be given with caution in patients with a diagnosis of or suspicious symptomatology for pheochromocytoma, as this might predispose these patients to episodes of paradoxical hypertension [64].…”

“…Neurologic side effects such as extrapyramidal symptoms and neuroleptic malignant syndrome (NMS) have been observed after butyrophenone administration [64,72]. Droperidol also has been associated with dysphoria, hallucinations, drowsiness, restlessness, hyperactivity and anxiety [64].…”

“…The i.v. injection is not FDA approved and QT evaluations are advised [63,64]. Droperidol is available as an i.v.…”

“…Per oral butyrophenones have not been used to treat PONV or CINV. The butyrophenones have high lipid solubility, which helps facilitate their CNS availability and activity [63,64].…”

Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms

“…Авторы метаанализа пришли к заключению, что пациен-ты с генотипом Val/Val имеют на 51% более высокий риск развития поздней дискинезии. Данный полиморфизм был изучен и в рамках острых экстрапирамидных расстройств [87].…”