Among antipsychotics, aripiprazole may be the best option for minimizing risks of hyponatremia—low levels of sodium in the body—according to a study published in JAMA Network Open.Why It’s Relevant
While discussions of antipsychotic side effects focus on weight gain or extrapyramidal symptoms, hyponatremia is known to occur in up to 6% of antipsychotic-treated patients and poses significant risks. Even mild cases of sodium deficiency can lead to medical deterioration and hospitalization. Few studies have examined the relative risks of hyponatremia among antipsychotics.
By the Numbers
- Researchers in Japan compiled data on antipsychotic-associated hyponatremia occurrences using both a pharmaceutical adverse event reporting database and hospital-based administrative claims.
- Relative to olanzapine—chosen as the reference because it had the most reports in the pharmaceutical database—aripiprazole demonstrated a 48% reduced risk of hyponatremia.
- Blonanserin, brexpiprazole, quetiapine, perospirone, and risperidone were not statistically different from olanzapine (blonanserin and perospirone are not approved in the United States).
What’s More
Based on pharmaceutical data, lurasidone was associated with a very low risk of hyponatremia. However, there were not enough patients prescribed the medication in the claims database to include it in the full analysis.
The Other Side
The outcome data was based on ICD-10 codes and not clinical assessments, which may have resulted in some misclassification. As claims data lack certain clinical details (such as disease severity), it is possible that patients prescribed each antipsychotic were clinically different.
Takeaway Message
The researchers noted that aripiprazole’s reduced risk may arise from it being a weaker activator of the dopamine D2 receptor than other assessed medications; the D2 receptor is linked with the production of antidiuretic hormones. Further comparative studies are needed, but this study may help inform medication selection for patients at high risk of hyponatremia.
Related Information
Source
Masakazu Hatano, et al. Comparative risk of hyponatremia among patients treated with second-generation antipsychotics. JAMA Network Open. Published August 13, 2026. doi:10.1001/jamanetworkopen.2026.28796
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