Can Risperidone Cause Hyponatremia?
Yes, risperidone can cause hyponatremia, though the risk appears lower compared to first-generation antipsychotics and some other second-generation agents. The FDA label specifically documents seizures occurring in association with hyponatremia in risperidone-treated patients, and the mechanism is presumed to be syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1.
Evidence Quality and Risk Assessment
The evidence linking risperidone to hyponatremia comes from multiple sources with varying strength:
FDA labeling explicitly mentions seizures occurring "in association with hyponatremia" in risperidone-treated patients, establishing this as a recognized adverse effect 1.
Population-based data from a large Swedish case-control study (14,359 hyponatremia cases) found that risperidone was not associated with increased risk of hospitalization due to hyponatremia, with adjusted odds ratios of 0.86 for newly initiated therapy and 0.83 for ongoing therapy 2. This represents the highest quality evidence available.
Case reports document SIADH-induced hyponatremia with risperidone, including one case resulting in seizures, respiratory failure, and rhabdomyolysis 3, 4.
Cross-sectional data from a study of 150 psychiatric patients found risperidone had the highest percentage of hyponatremia among serotonin dopamine antagonists studied, though the overall prevalence was 6% for this drug class 5.
Clinical Context and Risk Stratification
The apparent contradiction between case reports and population data suggests risperidone's hyponatremia risk is real but relatively low compared to other antipsychotics:
First-generation antipsychotics carry higher risk (adjusted OR 2.12) than second-generation agents (adjusted OR 1.32) 2.
Among second-generation antipsychotics, risperidone appears safer than some alternatives, with no statistically significant increased risk in the largest available study 2.
The combination of risperidone with SSRIs (particularly fluoxetine + risperidone) may increase hyponatremia risk 5.
Monitoring Recommendations
Check baseline serum sodium before initiating risperidone, particularly in high-risk patients 3, 6. High-risk features include:
Age >65 years: Older patients had maximum hyponatremia cases (66.66% in the 66-75 age group) 5.
Female sex: Women had higher rates (20.31%) compared to the overall population 5.
Concomitant medications: SSRIs, carbamazepine, and other drugs associated with SIADH significantly increase risk 7, 3.
Polydipsia history: Present in 67% of antipsychotic-induced hyponatremia cases 6.
Monitor serum sodium if symptoms develop: confusion, lethargy, seizures, or unexplained neurological changes 1, 4.
Management of Confirmed Hyponatremia
When SIADH is confirmed in a patient taking risperidone:
Discontinue risperidone immediately and implement fluid restriction with adequate oral salt intake 7, 3.
Consider alternative antipsychotics: Aripiprazole showed no increased risk in population studies (OR 0.62 for ongoing therapy) 2. Clozapine has been used successfully after risperidone-induced hyponatremia 3.
Avoid polypharmacy: The combination of risperidone with carbamazepine or SSRIs increases SIADH risk 3, 5.
Important Caveats
The American Geriatrics Society Beers Criteria notes that tramadol was added to the list of drugs associated with hyponatremia/SIADH, but does not specifically list risperidone, suggesting it may not be among the highest-risk agents in geriatric populations 7.
Most drug-induced hyponatremia cases are asymptomatic and discovered incidentally, meaning the true incidence may be higher than reported 6, 5.
Healthcare providers should maintain high clinical suspicion, as the incidence of antipsychotic-induced hyponatremia "may be much higher than is currently thought" 6.