Can Wellbutrin (bupropion) cause hyponatremia?

Bupropion and Hyponatremia: Risk Assessment and Management

Bupropion (Wellbutrin) can rarely cause hyponatremia, particularly in elderly patients, those on multiple medications, or patients with other risk factors for electrolyte disturbances. While not listed as a common side effect in the FDA drug label, there are several case reports documenting this association.

Risk Factors for Bupropion-Associated Hyponatremia

• Age: Elderly patients (>65 years) are at higher risk 1, 2
• Sex: Female patients appear more susceptible 2
• Medication combinations:
  • Concurrent use with other antidepressants 1
  • Combination with diuretics 2
• Other factors:
  • Low BMI
  • Pre-existing renal impairment
  • Polypharmacy

Mechanism of Hyponatremia with Bupropion

The exact mechanism is not fully established, but may involve:

1. Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) 1
2. Medication interactions when used as an augmentation strategy 1
3. Direct effects on renal sodium handling

Clinical Presentation

Hyponatremia associated with bupropion typically develops within the first 2 weeks of treatment 2 and may present as:

• Confusion
• Lethargy
• Headache
• Nausea
• Seizures (in severe cases)

Monitoring Recommendations

For patients starting bupropion:

• Check baseline sodium levels before initiating treatment
• Monitor sodium levels within the first 2 weeks of treatment 2
• Maintain vigilance throughout treatment, especially in high-risk patients
• Consider more frequent monitoring in elderly patients or those on diuretics

Management of Bupropion-Associated Hyponatremia

If hyponatremia develops:

1. Discontinue bupropion - Sodium levels typically normalize after discontinuation 3
2. Consider alternative antidepressants with lower risk of hyponatremia:
   • Mirtazapine appears to have a lower risk of hyponatremia 2
   • Bupropion is actually considered a safer alternative for patients who developed hyponatremia on SSRIs 4, but in this case would need to be discontinued

Prevention Strategies

• Careful patient selection
• Avoid combining with other medications known to cause hyponatremia when possible
• Patient education about symptoms requiring medical attention
• Regular monitoring of electrolytes in high-risk patients

Clinical Pearls

• Symptoms of hyponatremia can be misinterpreted as worsening depression 2
• The risk of hyponatremia appears higher when bupropion is used as an augmentation strategy with other antidepressants 1
• Hyponatremia is more commonly associated with SSRIs than with bupropion, making bupropion a potential alternative for patients who developed hyponatremia on SSRIs 4
• Seizure risk with bupropion (0.1%) may be exacerbated by hyponatremia, as hyponatremia itself lowers seizure threshold 5

While bupropion is not commonly associated with hyponatremia compared to SSRIs, clinicians should remain vigilant, especially when prescribing to elderly patients or those with other risk factors for electrolyte disturbances.