Fluoxetine and Hyponatremia
Yes, fluoxetine can cause hyponatremia, particularly in elderly patients, as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). 1
Mechanism and Risk
- Hyponatremia associated with fluoxetine appears to be the result of SIADH, with cases reporting serum sodium levels as low as 110 mmol/L 1
- The FDA drug label explicitly states that hyponatremia may occur as a result of treatment with SSRIs including fluoxetine (Prozac) 1
- Elderly patients are at particularly higher risk of developing this adverse effect 1, 2
- Patients taking diuretics or who are otherwise volume depleted may also be at greater risk 1
Incidence and Timing
- In elderly populations, the reported incidence of hyponatremia with fluoxetine is approximately 6.3 per 1000 treated patients per year 3
- Hyponatremia typically develops early in treatment, with a median onset of 13.5 days (range 4-64 days) after starting the medication 3
- In one study, 28% of elderly patients on fluoxetine developed hyponatremia 4
Risk Factors
- Advanced age (elderly patients) 1, 2, 3
- Female gender (women appear more susceptible) 2, 3
- Low body weight is a significant risk factor (mean weight of affected patients was 53.0 kg compared to 64.5 kg in controls) 3
- Concomitant use of diuretics 1
- Volume depletion 1
Clinical Presentation
- Signs and symptoms of hyponatremia include: 1
- Headache
- Difficulty concentrating
- Memory impairment
- Confusion
- Weakness
- Unsteadiness (which may lead to falls)
- More severe cases may present with: 1
- Hallucinations
- Syncope
- Seizures
- Coma
- Respiratory arrest
- Death
Management
- Discontinuation of fluoxetine should be considered in patients with symptomatic hyponatremia 1
- Appropriate medical intervention should be instituted for symptomatic patients 1
- Monitoring serum sodium levels is advisable, especially in elderly patients during the first few weeks of therapy 2, 4
- Withdrawal of fluoxetine is associated with recovery in most cases 2
Monitoring Recommendations
- Monitor electrolytes in older patients, particularly during the first weeks of therapy 2
- Serum sodium should be measured before commencing fluoxetine and monitored during the first month of treatment 4
- Any patient who exhibits symptoms of hyponatremia or whose depression apparently worsens while on fluoxetine should have their serum sodium measured 4
Alternative Treatment Options
- For patients at high risk for hyponatremia, consider alternative antidepressants with potentially lower risk profiles for this specific adverse effect, such as bupropion 5
This adverse effect is not unique to fluoxetine but appears to be a class effect of SSRIs, with similar reports for paroxetine and citalopram 3, 6, 7.