Paroxetine-Induced Hyponatremia: Incidence and Risk Factors

Approximately 12% of patients taking paroxetine develop hyponatremia, with elderly patients being at particularly high risk. 1

Incidence and Timing

Hyponatremia occurs in about 12% of older adults taking paroxetine, with symptoms typically developing within 9-14 days after initiation of therapy 1
The mean time to development of hyponatremia is 9.3 ± 4.7 days (median 9 days) after starting paroxetine 1
Hyponatremia can also occur upon resumption of paroxetine therapy after a period of discontinuation 2

Lower body mass index is a significant risk factor for developing hyponatremia 1
Lower baseline plasma sodium level (<138 mEq/L) increases risk of developing hyponatremia 1
Advanced age is a major risk factor, with most reported cases involving elderly patients 3, 4
The risk appears higher in elderly women than men, though both can be affected 5

Paroxetine-induced hyponatremia typically presents as Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) 3, 4
The exact mechanism is not fully understood, but involves dysregulation of antidiuretic hormone (ADH) leading to water retention and dilutional hyponatremia 4
Laboratory findings typically include hyponatremia, serum hypoosmolality, and urine hyperosmolality 2

Symptoms can include confusion, fatigue, and altered mental status 2
Severe hyponatremia can lead to seizures, coma, and potentially death if not properly managed 6
Many patients may be asymptomatic, especially with mild hyponatremia, making regular monitoring essential 3

For mild hyponatremia without symptoms, monitoring and water restriction may be sufficient 6
For moderate hyponatremia, water restriction to 1,000 mL/day and consideration of discontinuing paroxetine 6
For severe hyponatremia, discontinuation of paroxetine and initiation of intravenous normal saline along with fluid restriction 2
The rate of sodium correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 6

Regular monitoring of serum sodium levels is essential, particularly in high-risk patients 4
Recommended monitoring schedule: baseline sodium level before initiating paroxetine and follow-up measurements after 1,2,4,6, and 12 weeks of treatment 1
Closer monitoring is warranted in patients with risk factors such as advanced age, low body mass index, or baseline sodium <138 mEq/L 1
Monitor for clinical symptoms of hyponatremia, especially if a patient's condition deteriorates after starting paroxetine 3

Hyponatremia is an under-recognized but potentially serious complication of paroxetine treatment, especially in older adults 1
Clinicians should maintain a high index of suspicion for hyponatremia in elderly patients on paroxetine who develop new neurological or psychiatric symptoms 3
Consider alternative antidepressants in patients at high risk for developing hyponatremia 7