Does Prozac Cause Low Sodium?
Yes, Prozac (fluoxetine) can cause hyponatremia, particularly in elderly patients, and this risk is highest within the first 3 weeks of treatment. 1
Mechanism and FDA Recognition
- The FDA drug label explicitly states that hyponatremia may occur as a result of treatment with SSRIs including Prozac, often due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). 1
- Cases with serum sodium lower than 110 mmol/L have been reported and are reversible when Prozac is discontinued. 1
High-Risk Populations
Elderly patients are at substantially greater risk of developing SSRI-induced hyponatremia. 1
- In elderly women (ages 68-88 years), the reported rate of hyponatremia on fluoxetine 20 mg daily was 8.5 per 1000 patients. 2
- The overall incidence in elderly populations is approximately 4.7 per 1000 people treated per year (6.3 per 1000 for fluoxetine specifically). 3
- Older patients (>55 years) experience more frequent, more severe, and more clinically manifested hyponatremia compared to younger patients (ages 15-35). 4
Additional risk factors include: 1, 3
- Low body weight (mean 53 kg in cases vs 64.5 kg in controls)
- Female gender (71% of cases were women)
- Concurrent diuretic use
- Volume depletion from any cause
Timeline of Onset
Hyponatremia typically develops early in treatment:
- Most cases occur within the first 3 weeks of therapy, with median onset at 13.5 days (range 4-64 days). 3
- Five of seven reported cases in one series developed hyponatremia within 19 days of starting fluoxetine. 2
- In older patients, significant sodium decreases can be detected as early as the first week of therapy. 4
Clinical Presentation
Signs and symptoms range from mild to life-threatening: 1
- Mild: headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness leading to falls
- Severe: hallucinations, syncope, seizures, coma, respiratory arrest, and death
- One case report documented a patient presenting with confusion, vomiting, unresponsiveness, and generalized seizure with serum sodium of 105 mmol/L. 5
Monitoring Recommendations
Monitor serum sodium levels in high-risk patients during the first 3 weeks of fluoxetine therapy. 4, 3
- This is particularly critical for patients over 55 years of age. 4
- The American College of Physicians notes that while evidence is scarce, hyponatremia should be considered when treating patients with SSRIs. 6
Management
Discontinue Prozac in patients with symptomatic hyponatremia and institute appropriate medical intervention. 1
- Withdrawal of fluoxetine is associated with recovery in all reported cases. 2
- Serum sodium typically normalizes within 5 days of discontinuation, with mental status returning to baseline as hyponatremia resolves. 5
Special Clinical Contexts
In patients with heart failure: Alternative causes of hyponatremia should be assessed first, and water restriction with maximization of guideline-directed medical therapy should be attempted before attributing hyponatremia solely to SSRI use. 6
In patients with liver cirrhosis: The primary concern is typically hypervolemic hyponatremia from underlying liver disease rather than SSRI-induced SIADH. 6
Critical Pitfall to Avoid
Do not dismiss new-onset confusion, weakness, or neurological symptoms in elderly patients on fluoxetine as simply "depression" or "aging"—check serum sodium immediately, as severe hyponatremia can present with seizures and altered mental status requiring urgent intervention. 5