JAMA Netw Open
Combining antipsychotics and SSRIs linked to higher arrhythmia risk
Clinical Takeaway: When initiating an SSRI in patients already taking an antipsychotic—especially QT‑prolonging agents—review cardiac risk, consider ECG monitoring, and weigh alternatives when possible.
In this large cohort study, researchers analyzed insurance claims data from more than 300,000 US adults and 170,000 adults in Taiwan to examine cardiac risk when SSRIs are added to antipsychotic therapy. Using a sequential target trial emulation, the study followed patients for up to one year after SSRI initiation.
Concurrent antipsychotic and SSRI use was associated with a significantly higher risk of ventricular arrhythmia or sudden death compared with antipsychotic therapy alone. Adjusted hazard ratios were 1.51 in the US cohort and 3.32 in the Taiwan cohort, despite events remaining uncommon overall. Among SSRIs, citalopram and escitalopram carried the highest risk, with hazard ratios of 2.20 and 2.84, respectively.
“Although ventricular arrhythmia or sudden death events were rare, their potential severity underscores the importance of cautious prescribing and monitoring,” the authors wrote. Findings were consistent across multiple sensitivity analyses and subgroups, reinforcing concerns about additive or synergistic QT‑prolonging effects.
For clinicians, the study highlights the need for thoughtful medication selection and proactive cardiac safety monitoring when combining these commonly co‑prescribed drug classes.
Source: Chien HT, et al. (2026, April 9). JAMA Netw Open. Ventricular Arrhythmia and Sudden Death Risk With Concomitant Antipsychotic and SSRI Use