What medications are most commonly associated with causing hyponatremia (low sodium levels)?

From the Guidelines

Medications most commonly associated with hyponatremia include thiazide diuretics, selective serotonin reuptake inhibitors (SSRIs), antiepileptic drugs, antipsychotics, certain antibiotics, proton pump inhibitors, NSAIDs, and chemotherapeutic agents. These medications can cause hyponatremia through various mechanisms, including the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or by impairing the kidney's diluting capacity and increasing antidiuretic hormone (ADH) activity 1. Some of the specific medications known to cause hyponatremia include:

• Thiazide diuretics: hydrochlorothiazide, chlorthalidone, and indapamide
• SSRIs: fluoxetine, sertraline, and escitalopram
• Antiepileptic drugs: carbamazepine, oxcarbazepine, and sodium valproate
• Antipsychotics: haloperidol, risperidone
• Certain antibiotics: trimethoprim-sulfamethoxazole
• Proton pump inhibitors: omeprazole, pantoprazole
• NSAIDs
• Chemotherapeutic agents: cyclophosphamide, vincristine The risk of hyponatremia is higher in elderly patients, those with renal impairment, and when multiple at-risk medications are used simultaneously 1. It is essential to monitor sodium levels during the first few weeks of starting these medications, especially in high-risk patients, as hyponatremia typically develops during this period. The treatment of hyponatremia often involves addressing the underlying cause, and in some cases, the use of vasopressin antagonists such as tolvaptan or conivaptan may be considered, especially in patients with severe hypervolemic hyponatremia 1.

From the FDA Drug Label

Hyponatremia — Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Prozac. The medications most known to cause hyponatremia are SSRIs and SNRIs, including Prozac 2.

• Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs.
• Patients taking diuretics or who are otherwise volume depleted may be at greater risk.

From the Research

Medications Known to Cause Hyponatremia

• Thiazide diuretics: These medications can induce hyponatremia by impairing urinary dilution, renal loss of sodium and potassium, stimulating antidiuretic hormone (ADH), and perhaps from a dipsogenic effect 3, 4.
• Selective serotonin reuptake inhibitors (SSRIs): SSRIs can cause hyponatremia through the syndrome of inappropriate ADH release 3, 5, 6, 7.
• Serotonin dopamine antagonists (SDAs): SDAs can also contribute to the development of hyponatremia, especially when used in combination with SSRIs 7.

Risk Factors for Hyponatremia

• Concurrent use of thiazide diuretics and SSRIs: This combination is associated with an increased risk of hyponatremia in older populations 6.
• Older age: Older adults are at a higher risk of developing hyponatremia, especially when taking SSRIs or thiazide diuretics 4, 6, 7.
• Female sex: Females have a higher risk of developing hyponatremia, especially when taking SSRIs or SDAs 7.
• Comorbidities: Patients with heart failure, liver disease, or malignancy are at a higher risk of developing thiazide-associated hyponatremia 4.

Prevalence of Hyponatremia

• The prevalence of hyponatremia was 10.4% in patients taking thiazides alone and 9.0% in those taking SSRIs alone 6.
• Patients on both thiazide diuretics and SSRIs had a hyponatremia prevalence of approximately 13.0% 6.
• The adjusted odds ratio (OR) of hyponatremia with concomitant use of thiazide diuretics was 1.24 (95% CI: 1.22-1.26) among SSRI users, and 1.27 (95% CI: 1.24-1.29) among thiazide users 6.