Which Selective Serotonin Reuptake Inhibitor (SSRI) does not cause hyponatremia?

From the Guidelines

All SSRIs have the potential to cause hyponatremia, and there is no single SSRI that does not carry this risk. According to the study published in the American Family Physician in 2015 1, hyponatremia is a potential adverse effect associated with SSRIs, with a risk of 0.5% to 12% in older adults. The study found that SSRIs have an odds ratio of 3.3 (95% CI, 1.3 to 8.6) for causing hyponatremia compared to other drug classes.

Key Points to Consider

• The risk of hyponatremia varies among different SSRIs, but all SSRIs carry this risk to some extent 1.
• Escitalopram and citalopram may have a lower risk of causing hyponatremia compared to other SSRIs like fluoxetine, paroxetine, and sertraline, but this does not mean they are completely safe 1.
• The mechanism behind SSRI-induced hyponatremia involves inappropriate antidiuretic hormone secretion (SIADH), which leads to water retention and dilution of sodium in the blood.
• Monitoring sodium levels is advisable when prescribing any SSRI, especially during the first few weeks of treatment and in high-risk populations, such as the elderly and those taking diuretics 1.

Clinical Implications

• When prescribing SSRIs, it is essential to be aware of the potential risk of hyponatremia and to monitor patients accordingly 1.
• If a patient has a history of hyponatremia with one SSRI, switching to another SSRI like escitalopram might be reasonable, but vigilant monitoring remains necessary 1.
• The study highlights the importance of considering the potential adverse effects of SSRIs, including hyponatremia, when selecting a medication for patients with depression 1.

From the Research

Selective Serotonin Reuptake Inhibitors (SSRIs) and Hyponatremia

• The provided studies do not specify an SSRI that does not cause hyponatremia, but rather highlight the risk of hyponatremia associated with various SSRIs, including citalopram 2, 3, 4 and sertraline 5, 6.
• Citalopram has been reported to cause hyponatremia in several cases, with a higher risk in elderly females and patients with lower body weight 2.
• A retrospective observational study found that 16.5% of patients developed hyponatremia after starting citalopram treatment, with significant associations with lower baseline sodium, older age, thiazide diuretic use, and male sex 3.
• Sertraline has also been reported to cause hyponatremia, and replacing it with a non-serotonergic antidepressant (bupropion) led to full recovery in one case 5.
• A register-based case-control study found a strong association between newly initiated treatment with SSRIs (including citalopram and sertraline) and hospitalization due to hyponatremia, but no evidence that ongoing treatment with antidepressants increases this risk 6.

Comparison of SSRIs

• The studies suggest that different SSRIs may have varying degrees of association with hyponatremia, but do not identify a specific SSRI that does not cause hyponatremia 6.
• Tricyclic antidepressants and mirtazapine were found to have a small to moderate association with hospitalization due to hyponatremia, compared to SSRIs 6.
• Venlafaxine, a non-SSRI antidepressant, was also found to have a strong association with hospitalization due to hyponatremia 6.