Can Wellbutrin (bupropion) cause hyponatremia?

Can Wellbutrin (Bupropion) Cause Hyponatremia?

Yes, bupropion can cause hyponatremia, though this is a rare adverse effect documented primarily in case reports rather than large-scale studies.

Evidence for Bupropion-Induced Hyponatremia

The FDA drug label for bupropion identifies hyponatremia as a metabolic disorder that can increase seizure risk when present, but does not explicitly list it as a direct adverse effect of the medication 1. However, multiple case reports have documented this association:

• A 75-year-old man developed hyponatremia with bupropion use, which resolved upon discontinuation 2
• A 72-year-old woman experienced hyponatremia associated with bupropion treatment 3
• A 60-year-old man in Korea developed severe hyponatremia after bupropion treatment for depression 4

Mechanism and Clinical Context

The mechanism of bupropion-induced hyponatremia likely involves nephrogenic syndrome of inappropriate antidiuresis (NSIAD), where intrarenal activation of water reabsorption occurs with suppressed plasma AVP levels 5. This differs from classic SIADH and represents the major mechanism for drug-induced hyponatremia with many psychotropic agents 5.

Risk Factors to Monitor

High-risk patients include those with:

• Age >65 years 3
• Female sex 3
• Concurrent diuretic use 3
• Low BMI 3
• Pre-existing metabolic disorders 1

Clinical Monitoring Recommendations

Check serum sodium levels:

• Within the first 2 weeks after initiating bupropion, especially in high-risk patients 3
• At any time if unexplained mental status changes occur during treatment 3
• Before dose escalation in patients with risk factors 1

Management Approach

If hyponatremia develops:

• Discontinue bupropion immediately 2, 4
• Assess severity and symptom acuity (acute <48 hours vs chronic >48 hours) 6
• Consider switching to mirtazapine, which has low risk for hyponatremia and may be helpful in patients who developed hyponatremia with other antidepressants 3

Important Caveats

The association between bupropion and hyponatremia is significantly less common than with other antidepressants, particularly SSRIs 3. The limited evidence consists primarily of isolated case reports rather than systematic studies 2, 3, 4. However, the clinical consequences can be serious if missed, as symptoms may be misinterpreted as worsening psychiatric illness 3.

The seizure risk from hyponatremia compounds bupropion's inherent dose-related seizure risk, making early detection particularly critical 1.