Does Luvox (fluvoxamine) cause hyponatremia?

Does Luvox (Fluvoxamine) Cause Hyponatremia?

Yes, Luvox (fluvoxamine) can cause hyponatremia, and this is a well-documented adverse effect that requires clinical vigilance, particularly in elderly patients and those on diuretics.

Mechanism and Clinical Evidence

Fluvoxamine causes hyponatremia primarily through the syndrome of inappropriate antidiuretic hormone secretion (SIADH). 1 The FDA drug label explicitly warns that hyponatremia may occur as a result of treatment with SSRIs, including fluvoxamine, and in many cases appears to be the result of SIADH, with cases reported where serum sodium dropped below 110 mmol/L 1.

• Published case series have documented severe hyponatremia (serum sodium 103-112 mEq/L) in patients taking fluvoxamine, with onset ranging from 3 days to 3 months after initiation 2.
• High plasma AVP (antidiuretic hormone) levels observed in these cases suggest that SSRIs directly stimulate AVP secretion, thereby causing SIADH 2.
• A comprehensive review identified 736 cases of hyponatremia and SIADH associated with SSRI use, with fluvoxamine accounting for 1.5% (11 cases) of reported cases 3.

High-Risk Populations

Elderly patients are at particularly high risk for developing fluvoxamine-induced hyponatremia. 1

• The FDA label specifically states that elderly patients may be at greater risk of developing hyponatremia with SSRIs 1.
• Published case reports show that 83% of cases involved patients 65 years or older 3.
• Patients taking diuretics or who are otherwise volume depleted are at greater risk 1.
• Additional risk factors include female gender, low body weight, and lower baseline serum sodium concentration 4.

Time Course and Clinical Presentation

Hyponatremia typically develops within the first few weeks of fluvoxamine treatment, though delayed onset is possible. 4

• The median time to onset is 13 days (range 3 to 120 days) 3.
• One case report documented severe hyponatremia (serum sodium <114 mmol/L) in a 49-year-old man, demonstrating that younger patients are not immune 5.
• Signs and symptoms include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls 1.
• More severe cases can present with hallucination, syncope, seizure, coma, respiratory arrest, and death 1.

Clinical Management

Discontinuation of fluvoxamine should be considered in patients with symptomatic hyponatremia, and appropriate medical intervention should be instituted. 1

• Treatment includes discontinuation of fluvoxamine and administration of hypertonic saline for severe cases 2, 5.
• Serum sodium levels typically normalize within 2 weeks after therapy is discontinued 4.
• For isovolemic hypotonic hyponatremia, treatment includes water restriction and mild diuresis with a loop diuretic 4.
• More severe cases may require higher doses of loop diuretics and hypertonic saline 4.

Important Considerations for Switching SSRIs

Switching from fluvoxamine to another SSRI does not eliminate the risk of hyponatremia. 6

• One case report documented delayed recurrent hyponatremia 16 months after switching from fluvoxamine to paroxetine 6.
• However, another case successfully transitioned to citalopram without recurrence of hyponatremia 5.
• Plasma sodium concentrations must be monitored not only in the first weeks of treatment but throughout the full course of any SSRI therapy 6.

Monitoring Recommendations

Baseline and periodic monitoring of serum sodium is essential, especially in high-risk patients. 4

• Monitor serum sodium before initiating fluvoxamine in elderly patients, those on diuretics, or those with low body weight 4.
• Increased vigilance is warranted during the first 2-4 weeks of treatment when risk is highest 3, 4.
• Any patient presenting with confusion, weakness, falls, or altered mental status while on fluvoxamine should have immediate serum sodium assessment 1.

Common Pitfalls

• Failing to recognize that fluvoxamine is specifically mentioned alongside paroxetine and sertraline as having greater potential for discontinuation syndrome, suggesting it may have more pronounced effects on electrolyte balance 7.
• Assuming younger patients are not at risk—while elderly patients are at highest risk, severe hyponatremia can occur in middle-aged adults 5.
• Believing that switching to another SSRI eliminates risk—hyponatremia can recur with different SSRIs, sometimes after prolonged periods 6.
• Neglecting to monitor sodium levels beyond the initial weeks of treatment—delayed onset cases have been documented 6, 3.