Khan Qasim, Ismail Mohammad, Haider Iqbal, Khan Fahadullah
Department of Pharmacy, University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan.
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Int J Clin Pharm. 2017 Dec;39(6):1256-1264. doi: 10.1007/s11096-017-0532-5. Epub 2017 Sep 12.
Background QT prolongation and associated arrhythmias, torsades de pointes (TdP), are considerable negative outcomes of many antipsychotic and antidepressant agents frequently used by psychiatric patients. Objective To identify the prevalence, levels, and predictors of QT prolonging drug-drug interactions (QT-DDIs), and AZCERT (Arizona Center for Education and Research on Therapeutics) classification of drugs involved in QT-DDIs. Setting Psychiatry wards of three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Method This was a multicenter cross-sectional study. Micromedex DrugReax was used for identification of QT-DDIs. TdP risks were identified by the AZCERT classification. Multivariate logistic regression analysis was performed to identify predictors of QT-DDIs. Main outcome measure Prevalence of QT-DDIs (overall, age-wise and gender-wise) and their levels of severity and documentation; AZCERT classes of drugs involved in QT-DDIs; and odds ratios for predictors of QT-DDIs. Results Of 600 patients, 58.5% were female. Median age was 25 years (IQR = 20-35). Overall 51.7% patients had QT-DDIs. Of total 698 identified QT-DDIs, most were of major-severity (98.4%) and fair-documentation (93.7%). According to the AZCERT classification, 36.4% of the interacting drugs were included in list-1 (known risk of TdP), 26.9% in list-2 (possible risk of TdP) and 27.5% in list-3 (conditional risk of TdP). Drugs commonly involved in QT-DDI were olanzapine (n = 146), haloperidol (138), escitalopram (122), risperidone (91), zuclopenthixol (87), quetiapine (n80) and fluoxetine (74). In multivariate logistic regression analysis, QT-DDIs were significantly associated with 6-7 prescribed medications (p = 0.04) and >7 medications (p = 0.03). Similarly, there was significant association of occurrence of QT-DDIs with 2-3 QT drugs (p < 0.001) and >3 QT drugs (p < 0.001). Conclusion A considerable number of patients are exposed to QT-DDIs in psychiatry. There is a need to implement protocol for monitoring the outcomes of QT-DDIs.
QT间期延长及相关心律失常,即尖端扭转型室速(TdP),是精神科患者常用的许多抗精神病药和抗抑郁药的严重不良后果。目的:确定QT间期延长药物相互作用(QT-DDI)的患病率、程度及预测因素,以及参与QT-DDI的药物的亚利桑那州教育与治疗研究中心(AZCERT)分类。地点:巴基斯坦开伯尔-普赫图赫瓦省三家主要三级医疗医院的精神科病房。方法:这是一项多中心横断面研究。使用Micromedex DrugReax识别QT-DDI。通过AZCERT分类确定TdP风险。进行多因素逻辑回归分析以确定QT-DDI的预测因素。主要结局指标:QT-DDI的患病率(总体、按年龄和按性别)及其严重程度和记录水平;参与QT-DDI的药物的AZCERT类别;以及QT-DDI预测因素的比值比。结果:600名患者中,58.5%为女性。中位年龄为25岁(四分位间距=20-35)。总体而言,51.7%的患者存在QT-DDI。在总共识别出的698例QT-DDI中,大多数为严重程度(98.4%)和记录良好(93.7%)。根据AZCERT分类,36.4%的相互作用药物被列入清单1(已知TdP风险),26.9%被列入清单2(可能的TdP风险),27.5%被列入清单3(有条件的TdP风险)。常见参与QT-DDI的药物有奥氮平(n=146)、氟哌啶醇(138)、艾司西酞普兰(122)、利培酮(91)、珠氯噻醇(87)、喹硫平(n=80)和氟西汀(74)。在多因素逻辑回归分析中,QT-DDI与6-7种处方药物(p=0.04)和>种药物(p=0.03)显著相关。同样,QT-DDI的发生与2-3种QT药物(p<0.001)和>3种QT药物(p<0.001)显著相关。结论:精神科有相当数量的患者暴露于QT-DDI。需要实施监测QT-DDI结局的方案。