Dosing of Wellbutrin (Bupropion) in Stage 3a CKD
For adult patients with Stage 3a CKD (eGFR 45-59 ml/min/1.73m²), Wellbutrin (bupropion) should be dosed at 150 mg every 3 days rather than the standard daily dosing used in patients with normal renal function.
Pharmacokinetic Considerations in CKD
Bupropion undergoes significant hepatic metabolism with three major metabolites:
- Hydroxybupropion
- Threohydrobupropion
- Erythrohydrobupropion
In patients with kidney disease, these metabolites can accumulate significantly:
- Research shows that while bupropion itself has pharmacokinetics similar to those with normal renal function, its metabolites demonstrate increased area under the curve, indicating significant accumulation in renal failure 1
- CKD affects non-renal clearance of drugs in addition to reducing renal clearance, with studies demonstrating that CYP2B1 (responsible for bupropion metabolism) is downregulated in CKD 2
Evidence-Based Dosing Recommendations
The pharmacokinetic study in hemodialysis patients who smoke demonstrated that:
- A single dose of 150 mg bupropion resulted in metabolite accumulation
- Based on these findings, researchers concluded that 150 mg every 3 days would be more appropriate than the manufacturer's recommendation of 150 mg daily in patients with renal impairment 1
For Stage 3a CKD specifically:
- While less severe than end-stage renal disease, the altered pharmacokinetics still warrant dose adjustment
- The European Renal Best Practice (ERBP) systematic review identified bupropion as one of the antidepressants requiring dose reduction in CKD stages 3-5 3
Monitoring Parameters
When initiating bupropion in patients with CKD:
- Monitor for signs of drug toxicity (agitation, insomnia, seizures)
- Assess therapeutic response after 1-3 weeks (typical onset of action) 4
- Consider potential drug interactions, particularly with medications commonly used in CKD
- Monitor kidney function regularly as recommended by KDIGO guidelines 5
Important Considerations and Precautions
- Bupropion has a lower risk of cardiovascular effects compared to other antidepressants, which may be beneficial in CKD patients who often have cardiovascular comorbidities 4
- The drug is non-sedating, which may be advantageous for patients with CKD who often experience fatigue
- Be cautious about seizure risk, which may be increased in patients with uremia
- Consider that bupropion may antagonize effects of commonly used sedatives 4
Alternative Options
If bupropion is not tolerated or contraindicated, consider other antidepressants with established safety profiles in CKD, though most will also require dose adjustment in renal impairment.
Remember that the management of depression is particularly important in CKD patients, as depression is associated with worse quality of life, increased hospitalization, and higher mortality in this population 3.