What medications can cause hyponatremia?

Leading Medications That Cause Hyponatremia

Thiazide diuretics are the most common medications that cause hyponatremia, followed by selective serotonin reuptake inhibitors (SSRIs), and carbamazepine. 1

Common Medications Associated with Hyponatremia

First-Line Offenders

1. Thiazide Diuretics

   • Most frequently implicated in drug-induced hyponatremia 1, 2
   • Hyponatremia develops within 14 days in most patients 2
   • Risk factors include:
     • Advanced age
     • Female sex
     • Low body weight
     • Hypokalemia 3

2. Selective Serotonin Reuptake Inhibitors (SSRIs)

   • Second most common cause 1
   • Mechanism: Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) 4
   • Fluoxetine and other SSRIs can cause hyponatremia through SIADH 4
   • Higher risk in elderly patients

3. Antiepileptic Drugs

   • Carbamazepine is particularly associated with hyponatremia 5
   • Risk appears to be dose-related 5
   • Mechanism: SIADH

Second-Line Offenders

1. Loop Diuretics

   • Lower risk than thiazides but still significant 1
   • Higher risk when combined with other medications 6

2. Other Psychotropic Medications

   • Antipsychotics
   • Mood stabilizers

3. Vasopressin Antagonists

   • Can paradoxically cause hyponatremia in certain contexts 1
   • Examples: conivaptan, tolvaptan, lixivaptan, satavaptan 6

Risk Factors for Medication-Induced Hyponatremia

1. Patient-Related Factors

   • Age > 65 years (each 10-year increment of age doubles the risk) 3
   • Female sex (4 times more common than in men) 2
   • Low body weight (5 kg decrease increases risk by 27%) 3
   • Hypokalemia 3

2. Medication-Related Factors

   • Combination therapy (multiple at-risk medications) 1
   • Higher medication doses
   • Duration of therapy (though hyponatremia can occur early in treatment)

3. Comorbidities

   • Heart failure
   • Liver cirrhosis
   • Renal dysfunction 1

Pathophysiologic Mechanisms

1. Thiazide Diuretics

   • Impair diluting capacity of distal tubule
   • Cause sodium and potassium depletion
   • Reduce free water clearance 7

2. SSRIs and Carbamazepine

   • Primarily cause SIADH
   • Increase ADH release or enhance its effect 4, 5

3. Loop Diuretics

   • Volume depletion
   • Activation of ADH 6

Clinical Implications and Management

• Monitor serum sodium levels in high-risk patients, especially within 2-4 weeks of starting at-risk medications 1
• Consider alternative medications in patients with history of hyponatremia
• Educate patients about symptoms of hyponatremia (headache, confusion, weakness, seizures) 6
• For symptomatic hyponatremia, discontinue the offending medication and implement appropriate sodium correction strategies 5

Prevention Strategies

• Use lower doses of at-risk medications in elderly, female, and low-weight patients
• Monitor electrolytes regularly in high-risk patients
• Consider combination therapy carefully, especially thiazides with SSRIs
• Educate patients about adequate but not excessive fluid intake

Understanding the medications most likely to cause hyponatremia and their mechanisms allows for better prevention, earlier detection, and more effective management of this common electrolyte disorder.