TOPLINE

Aripiprazole was associated with a lower risk for hyponatremia compared with olanzapine among patients treated with second-generation antipsychotics (SGAs), a new retrospective cohort study showed.

METHODOLOGY

• Researchers conducted a retrospective cohort study using data from the FDA Adverse Event Reporting System (1997-2023) to generate hypotheses about differences in hyponatremia risk among SGA users. Data from a Japanese hospital-based claims database (2008-2024) were used for testing the hypotheses. 
• SGAs analyzed included aripiprazole, blonanserin, brexpiprazole, perospirone, quetiapine, and risperidone. Olanzapine acted as the control medication.
• Data from 55,394 adults (mean age, 50.4 years; 53.4% women) with at least 180 days of active medical history preceding initial antipsychotic prescription and no history of antipsychotics or hyponatremia during that period were included. 
• Patients were monitored for up to 180 days after antipsychotic treatment initiation, with hyponatremia defined as any of the following: serum sodium level < 135 mEq/L, syndrome of inappropriate secretion of antidiuretic hormone, or hypo-osmolality and hyponatremia. 
• Covariates included demographics, comorbidities, concomitant medication use, care setting, and the number of serum sodium measurements within 180 days. 

TAKEAWAY

• Incidence rates of hyponatremia were highest for risperidone, followed by olanzapine and perospirone (66.2, 54.8, and 52.3 events per 1000 person-years, respectively). 
• Most antipsychotics had lower reporting odds ratios (RORs) for hyponatremia vs olanzapine, with brexpiprazole (ROR, 0.13) and lurasidone (ROR, 0.19) showing the lowest RORs. 
• After weighting, aripiprazole was associated with a significantly lower risk for hyponatremia than olanzapine (adjusted hazard ratio, 0.52), whereas other antipsychotics showed no significant differences. 
• The associations were consistent across various plasma sodium thresholds and grace periods for treatment discontinuation. 

IN PRACTICE

“These findings suggest that the risk of hyponatremia may differ among second-generation antipsychotics, potentially facilitating antipsychotic selection for patients at higher risk,” the investigators wrote.

SOURCE

The study was led by Masakazu Hatano, PhD, Fujita Health University School of Medicine, Toyoake, Japan. It was published online on August 13 in JAMA Network Open.

LIMITATIONS

The study was limited by the lack of denominator data, incomplete patient characteristics, inability to adjust for confounding factors, reliance on claims data, residual confounding, detection bias, potential exposure misclassification, and limited generalizability.

DISCLOSURES

The study was funded by the Research Foundation for Pharmaceutical Sciences. Disclosure information for the study investigators is available in the original study publication.

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