Prevalence of QT interval prolonging drug-drug interactions (QT-DDIs) in psychiatry wards of tertiary care hospitals in Pakistan: a multicenter cross-sectional study.

Abstract

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 25years (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.