OBJECTIVES AND METHODS: Psychotropic drugs may prolong the corrected QT interval (QTc), which has been associated with torsades de pointes (TdP). Our aim is to measure the relative impact of psychotropic drug use on TdP. A case-control study was conducted on 110 cases of confirmed TdP, and 330 matched controls. Hierarchical regression was performed by first including pre-identified risk factors (including demographic, medical conditions, and drugs such as antiarrhythmics) and then psychotropic drugs (antidepressants and antipsychotics). Population attributable risks (PAR) were calculated. RESULTS: At the time of admission, TdP was the primary, secondary, or complication diagnosis in 32.7 %, 30.9 %, and 36.4 % of cases, respectively. There were more patients with TdP who died during hospitalization compared to controls (7.3 % vs. 2.7 %, p <
0.05), but TdP was the cause of death in only two (1.8 %) of them. In our final regression model, age, hepatic and/or renal failure and antidepressant/antipsychotic drug monotherapy were not associated with TdP. On the other hand, the use of other QTc-prolonging drugs, female sex, left ventricular dysfunction, acute myocardial infarction, hypokalemia, and use of ≥ 2 antidepressants were all significantly associated with TdP, with PAR of 55.3 %, 41.8 %, 26.2 %, 13.0 %, 11.7 %, and 6.3 % respectively. CONCLUSIONS: In analyses adjusting for concomitant conditions/drugs, antidepressant or antipsychotic monotherapy was not associated with TdP while the use of ≥ 2 antidepressants was. However in terms of PAR, the use of other QTc-prolonging drug, including antiarrhythmics, sex, and left ventricular dysfunction carried a higher burden than the use of ≥2 antidepressants. These findings may inform and assist in balancing the risks and benefits of psychotropic drugs.