What antidepressants have a lower risk of causing hyponatremia?

From the FDA Drug Label

In patients with symptomatic hyponatremia, discontinue mirtazapine tablets and institute appropriate medical intervention Elderly patients, patients taking diuretics, and those who are volume- depleted may be at greater risk of developing hyponatremia [see Use in Specific Populations (8.5)]. Serotonergic antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see WARNINGS AND PRECAUTIONS (5.11)].

Antidepressants with a Risk of Hyponatremia:

• Mirtazapine 1
• Trazodone 2

Key Points:

• Both mirtazapine and trazodone have been associated with a risk of hyponatremia, particularly in elderly patients.
• There is no clear evidence to suggest that one antidepressant has a significantly lower risk of causing hyponatremia compared to others.
• It is essential to monitor patients for signs and symptoms of hyponatremia, especially in high-risk populations such as the elderly, those taking diuretics, and those who are volume-depleted.

From the Research

Antidepressants with a lower risk of causing hyponatremia include bupropion, as it works primarily on dopamine and norepinephrine pathways rather than serotonin, making it a safer option for patients at higher risk for hyponatremia, such as elderly individuals or those taking diuretics 3. When considering the risk of hyponatremia, it's essential to weigh the benefits and risks of each medication.

• Bupropion is generally considered a safer option due to its mechanism of action, which less commonly affects antidiuretic hormone (ADH) secretion.
• Mirtazapine, although initially thought to have a low risk of hyponatremia, has been shown in more recent studies to present a moderate risk, with an incidence of 3.26% 4.
• Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) carry a higher risk of hyponatremia due to their potential to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). The most recent and highest quality study, a systematic review published in 2021, highlights the importance of considering the risk of hyponatremia when prescribing antidepressants, particularly in elderly patients or those with other risk factors 4. Key points to consider when prescribing antidepressants to at-risk patients include:
• Monitoring sodium levels, particularly during the first few weeks of treatment when hyponatremia risk is highest.
• Being aware of the potential for medication interactions, which can increase the risk of hyponatremia, as seen in cases where bupropion was added to other medications 5.
• Considering nonserotonergic antidepressants, such as bupropion, as a first-line treatment option for patients at high risk of hyponatremia 3.