TOPLINE:

Initiating selective serotonin reuptake inhibitors (SSRI) during antipsychotic treatment was associated with 51% and 232% increased risk for ventricular arrhythmia (VA) or sudden death in US and Taiwan adult cohorts, respectively, a new study showed. The risk was particularly elevated in patients younger than 65 years or in those who used known-risk SSRI.

METHODOLOGY:

• A cohort study used sequential trial emulation to assess health insurance databases from the US (2010-2023) and Taiwan (2010-2021).
• The study included more than 300,000 adults with psychotic disorders from the US cohort (61% women; mean age, 47 years) and nearly 200,000 adults from the Taiwan cohort (55% women; mean age, 51 years); all had initiated an antipsychotic and had not used SSRI in the previous year.
• Participants were assessed weekly for the initiation of SSRI following the initiation of antipsychotics to assess the 1-year risk for VA or sudden death.
• Covariates included demographics, comorbidities, and concomitant drugs.

TAKEAWAY:

• VA or sudden death occurred in 0.1% of SSRI initiators and 0.1% of noninitiators in the US cohort and in 0.2% of both initiators and noninitiators in the Taiwan cohort.
• VA or sudden death risk was higher with the concurrent use of antipsychotics and SSRI vs use of antipsychotics alone in both cohorts (US cohort: adjusted hazard ratio [aHR], 1.51; P = .03; Taiwan cohort: aHR, 3.32; P < .001).
• The risk for VA or sudden death was doubled for the known-risk SSRI citalopram and escitalopram in the US cohort (aHR, 2.20; P = .001) and the Taiwan cohort (aHR, 2.84; P < .001). Conditional-risk SSRI were linked to an increased risk in the Taiwan cohort (aHR, 2.85; P < .001) only.
• The associated risk with concomitant use of antipsychotics and SSRI was more pronounced among patients younger than 65 years in both cohorts (aHRs, 2.14 and 5.32, respectively).

IN PRACTICE:

“These results suggest that although ventricular arrhythmia or sudden death events were rare, their potential severity underscores the importance of cautious prescribing and monitoring when SSRIs are initiated in patients receiving antipsychotics,” the investigators wrote.

SOURCE:

The study was led by Hsiu-Ting Chien, PhD, Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. It was published online on April 9 in JAMA Network Open.

LIMITATIONS:

The study was limited by modest event counts, an observational design with potential unmeasured and residual confounding, potential confounding by indication, lack of genetic data such as polymorphisms, and lack of assessment of antipsychotic or SSRI dose because it may not have been accurately captured in claims data.

DISCLOSURES:

The study was funded by a grant from the National Science and Technology Council given to one of the researchers. The investigators reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.