Can Risperidone Cause Hyponatremia?
Yes, risperidone can cause hyponatremia, though the risk appears lower compared to other antipsychotics, and the FDA specifically documents seizures occurring in association with hyponatremia in risperidone-treated patients.
Evidence from FDA Drug Label
The FDA label for risperidone explicitly states that during premarketing testing, seizures occurred in 0.3% of risperidone-treated patients, with two cases occurring "in association with hyponatremia" 1. This direct acknowledgment in the official drug labeling confirms that hyponatremia is a recognized adverse effect of risperidone treatment.
Population-Based Research Evidence
Lower Risk Compared to Other Antipsychotics
The most robust evidence comes from a large Swedish population-based case-control study examining 14,359 patients hospitalized with hyponatremia 2. This study found:
- Risperidone showed no increased risk of severe hyponatremia in multivariable analysis adjusting for confounding factors 2
- For newly initiated risperidone therapy (≤90 days): adjusted OR 0.86 (95% CI 0.56-1.31) 2
- For ongoing risperidone therapy: adjusted OR 0.83 (95% CI 0.67-1.02) 2
- In contrast, first-generation antipsychotics had an adjusted OR of 2.12 (1.83-2.46) for hyponatremia 2
Modest Risk in Older Adults
A Canadian population-based cohort study of 116,016 adults aged 65+ found that atypical antipsychotics as a class (including risperidone, olanzapine, and quetiapine) were associated with increased 30-day hospitalization risk for hyponatremia 3:
- Relative risk: 1.62 (95% CI 1.15-2.29) 3
- Absolute risk increase: 0.06% (95% CI 0.02-0.10%) 3
- This represents a modest increase compared to other psychotropic medications 3
Pattern Analysis in Clinical Practice
A smaller observational study examining hyponatremia patterns found that among serotonin dopamine antagonists, risperidone had the highest percentage of hyponatremia cases, though the overall prevalence was 6% for this drug class 4. The combination of fluoxetine + risperidone showed higher hyponatremia rates than risperidone alone 4.
Clinical Mechanism and Case Reports
Risperidone can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH) 5. A documented case report describes a patient with schizoaffective disorder who developed SIADH after initiating risperidone and carbamazepine, which resolved with drug discontinuation and fluid restriction 5.
Clinical Monitoring Recommendations
Monitor serum sodium levels in high-risk patients:
- Elderly patients (age 65+), who show higher susceptibility to hyponatremia with atypical antipsychotics 3
- Female patients, who demonstrate higher rates of hyponatremia (20.31% in one study) 4
- Patients on combination therapy, particularly with SSRIs or carbamazepine, which may potentiate hyponatremia risk 5, 4
- Patients with seizure history, as the FDA notes seizures occurred in association with hyponatremia in risperidone trials 1
Important Clinical Caveats
The evidence presents an apparent contradiction: The FDA label documents hyponatremia occurrence 1, and case reports confirm SIADH as a mechanism 5, yet the highest-quality population study found no statistically significant increased risk with risperidone specifically 2. This suggests that while hyponatremia can occur with risperidone, the risk is substantially lower than with first-generation antipsychotics and possibly lower than with other second-generation agents 2.
Baseline and periodic electrolyte monitoring is prudent, particularly during the first 90 days of therapy when risk may be highest, and especially in elderly patients, females, and those on concomitant medications that affect sodium balance 5, 4, 3.