One antipsychotic may carry lower hyponatremia risk

Clinical takeaway: For patients at increased risk of hyponatremia, aripiprazole may be a reasonable option. It was associated with about a 48% lower risk of hyponatremia than olanzapine in this large observational analysis.

Hyponatremia is a recognized adverse effect of antipsychotic therapy and has been associated with prolonged hospitalization, readmission, and mortality. Identifying lower-risk treatment options could help inform prescribing for vulnerable patients.

In a retrospective cohort study and pharmacovigilance analysis, investigators compared the risk of hyponatremia across individual second-generation antipsychotics using data from the FDA Adverse Event Reporting System (FAERS) and a large Japanese claims database.

The claims-based analysis included 55,394 new users of antipsychotics (mean age, 50 years; 53% women), drawn from more than 961,000 treated patients. During up to 180 days of follow-up, hyponatremia occurred in 366 patients (0.7%).

In the FAERS analysis, several agents, including aripiprazole, brexpiprazole, lurasidone, quetiapine, and risperidone, were associated with fewer reports of hyponatremia than olanzapine. However, after adjustment for baseline characteristics, comorbidities, and concomitant medications in the claims database, aripiprazole was the only antipsychotic that remained associated with a significantly lower risk. Patients receiving aripiprazole had an approximately 48% lower risk of developing hyponatremia than those receiving olanzapine. No significant differences were observed for brexpiprazole, quetiapine, risperidone, blonanserin, or perospirone.

“The results suggest an association between aripiprazole and a lower risk of hyponatremia compared with olanzapine in routine clinical practice,” the authors wrote. “These findings can facilitate the selection of antipsychotics in patients with risk factors for hyponatremia.”

The authors cautioned that residual confounding and differences in outcome ascertainment may have influenced results and emphasized the need for additional studies to confirm whether hyponatremia risk truly differs among individual antipsychotics.

Source: Hatano M, et al. (2026 Aug 13) JAMA Netw Open. Comparative Risk of Hyponatremia Among Patients Treated With Second-Generation Antipsychotics