Antidepressants and Hyponatremia

Hyponatremia, which occurs when serum sodium levels drop below 135 mmol/L, is more than an abnormal lab finding. It can pose serious health risks, particularly in older adults taking antidepressants.

Which antidepressants should we be concerned about?

• High on the radar: Research shows that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), especially paroxetine and venlafaxine, have the highest risk of causing hyponatremia (Viramontes TS et al, Consult Pharm 2016;31(3):139–150).
• Moderate alert: While monoamine oxidase inhibitors and tricyclic antidepressants are associated with hyponatremia, they are less likely to cause it than SSRIs and SNRIs.
• Relatively safer choices: Bupropion and mirtazapine tend to carry a lower risk.

The underlying cause of the link between hyponatremia and antidepressants is believed to be related to serotonin-induced secretion of the antidiuretic hormone, causing the syndrome of inappropriate antidiuretic hormone secretion (SIADH). However, the exact mechanism remains unclear.

Who faces the greatest risk?

Older adults are especially vulnerable, and specific attributes can heighten the risk even more:

• Medications: Concurrent use of diuretics or other drugs such as oxcarbazepine, carbamazepine, and second-generation antipsychotics (particularly olanzapine, risperidone, and clozapine).
• Physical attributes: Weighing under 60 kg or being registered female at birth.
• Health conditions: Chronic renal failure or hypertension.

Remember that hyponatremia is not uncommon in older adults on antidepressants, but it is not always due to the antidepressant. Consider other causes of hyponatremia (eg, kidney disease, heart failure, severe vomiting or diarrhea, hormonal changes). Some older adults also have chronic idiopathic hyponatremia.

Symptoms and treatment

Hyponatremia typically manifests within two to four weeks of starting or increasing the dose of an antidepressant.

For milder cases (125–134 mmol/L)

• Symptoms: Some patients may have no symptoms, while others exhibit nausea, dizziness, vomiting, and headaches. Chronic mild hyponatremia may lead to gait disturbances, muscle weakness, or cognitive impairment and a higher risk of falls.
• Treatment: If you know SIADH is the cause of hyponatremia, discontinue the offending drug, limit fluid intake to 1–1.5 liters/day, and monitor sodium levels. Hyponatremia will generally resolve within two weeks of stopping the offending medication.

For severe cases (<125 mmol/L)

• Symptoms: More alarming symptoms (eg, lethargy, unsteady movements, difficulty in speech, delirium).
• Treatment: Immediate medical intervention, potentially involving hospitalization and treatment with hypertonic saline.

Prevention is better than cure

Use of antidepressants in our older patients is common, so awareness of this potential side effect is crucial. Always educate patients about the risk of hyponatremia. Regularly ask about fluid intake and monitor sodium levels before initiating treatment with an SSRI/SNRI, then ask again within two weeks of treatment. For those most at risk, such as patients with a history of SIADH or critically low sodium, consider using bupropion or ­mirtazapine.