From the Guidelines
Sertraline can decrease sodium levels in the body, but only indirectly through the syndrome of inappropriate antidiuretic hormone secretion (SIADH), as noted in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1. This effect is not a direct result of sertraline's mechanism of action as a selective serotonin reuptake inhibitor (SSRI) but rather an uncommon side effect. The study highlights that euvolemic hyponatremia, which can be caused by medications like sertraline, is uncommon among patients with cirrhosis unless there is a specific cause, such as SIADH or severe hypothyroidism or adrenal insufficiency. Some key points to consider include:
- Hyponatremia, defined as a serum Na concentration ≤135 mEq/L, is present in nearly half of patients with cirrhosis and ascites, with over a fifth having serum Na levels ≤130 mEq/L, as reported in the study 1.
- Symptoms of hyponatremia, although infrequent in patients with cirrhosis, range from nausea, muscle cramps, gait instability, lethargy, headache, and dizziness to confusion and seizure, and improvement in hyponatremia is associated with reduced brain edema, as stated in the study 1.
- The standard dosing of sertraline (50-200 mg daily) for depression or anxiety disorders does not routinely cause sodium depletion in most patients, and regular monitoring of electrolytes is not typically required unless other risk factors for hyponatremia are present. Given the potential for sertraline to contribute to hyponatremia through SIADH, it is essential to monitor sodium levels in patients taking sertraline, especially in those with risk factors for hyponatremia, such as the elderly or those with cirrhosis and ascites, as emphasized in the 2021 practice guidance 1.
From the FDA Drug Label
Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including sertraline. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The FDA drug label suggests that sertraline can decrease sodium levels by potentially causing the syndrome of inappropriate antidiuretic hormone secretion (SIADH), leading to hyponatremia.
- Key points:
- Hyponatremia may occur as a result of treatment with sertraline.
- SIADH is a possible cause of hyponatremia in patients taking sertraline.
- Elderly patients and those taking diuretics or who are otherwise volume depleted may be at greater risk of developing hyponatremia 2
From the Research
Mechanism of Sertraline-Induced Hyponatremia
- The mechanism by which sertraline, a selective serotonin reuptake inhibitor (SSRI), causes hyponatremia is thought to be secondary to the development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) 3, 4, 5.
- In SIADH, the body retains too much water, leading to a dilution of sodium in the blood, resulting in hyponatremia 3, 4, 5.
Risk Factors for Hyponatremia
- Risk factors for the development of hyponatremia with SSRIs, including sertraline, include older age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration 3, 6.
- The concomitant use of thiazide diuretics with SSRIs, such as sertraline, may have a synergistic effect in impairing renal free water clearance, increasing the risk of hyponatremia 4.
Incidence of Hyponatremia
- The incidence of hyponatremia associated with sertraline and other SSRIs varies from 0.5% to 32% 3, with some studies reporting an incidence of 0.87% in the first 30 days and 10.5% in the first 3 years of treatment 7.
- Compared to other antidepressants, sertraline has been associated with a moderate risk of hyponatremia, with some studies suggesting that duloxetine and escitalopram may have a higher risk, while bupropion and paroxetine may have a lower risk 7.
Monitoring and Treatment
- Serum sodium levels should be monitored closely in patients at higher risk of hyponatremia, including the elderly and those taking diuretics 3, 5.
- Treatment of hyponatremia associated with sertraline and other SSRIs includes water restriction, mild diuresis with a loop diuretic, and in more severe cases, higher doses of loop diuretics and hypertonic saline 3.