Antipsychotics and severe hyponatremia: A Swedish population-based case-control study

Antipsychotics have been claimed to cause hyponatremia. The risk associated with individual antipsychotics, or groups (first-generation [FGAs] or second-generation [SGAs] antipsychotics), is not well-documented. The objective of this study was to investigate the association between antipsychotics and hospitalization due to hyponatremia.

The general Swedish population was the base of this register-based case-control study. Comparisons were made between patients hospitalized with a principal diagnosis of hyponatremia (n = 14,359) and matched controls (n = 57,383). Multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and socioeconomic factors was performed to investigate the association between hyponatremia and antipsychotic use. In addition newly initiated (≤90 days) or ongoing use was analysed separately.

Compared to controls, the adjusted OR (95%CI) for hospitalization due to hyponatremia was for any antipsychotic 1.67(1.5-1.86). Individuals on FGA were more likely to experience severe hyponatremia (2.12[1.83-2.46]) than those on any SGA (1.32[1.15-1.51]). No increased risks, neither as newly initiated nor ongoing therapy, were found for risperidone (0.86[0.56-1.31] and 0.83[0.67-1.02]) and aripiprazole (1.16[0.30-4.46] and 0.62[0.27-1.34]), respectively.

There was an association between antipsychotic therapy and hospitalization due to hyponatremia. The association was stronger for FGAs than SGAs. Risperidone was not associated with an increased risk.