Can sertraline and Wellbutrin (bupropion) be combined?

Combining Sertraline and Bupropion

Yes, sertraline and bupropion can be safely combined, and this combination is often used clinically to address treatment-resistant depression or to counteract sexual side effects of sertraline, though caution is needed due to potential drug interactions.

Pharmacological Rationale

The combination of sertraline (an SSRI) and bupropion (a norepinephrine-dopamine reuptake inhibitor) can be effective because they work through different neurotransmitter systems:

• Sertraline primarily affects serotonin reuptake
• Bupropion primarily affects dopamine and norepinephrine reuptake
• This dual mechanism may provide synergistic antidepressant effects 1

Clinical Applications

This combination is commonly used in two scenarios:

1. Treatment-resistant depression

   • When monotherapy with either medication has been inadequate
   • Case reports show efficacy in patients who failed trials of either medication alone 1

2. Managing SSRI-induced sexual dysfunction

   • Bupropion can counteract the sexual side effects of sertraline
   • Studies show significantly lower rates of sexual dysfunction with bupropion compared to sertraline 2, 3

Important Drug Interaction Considerations

When combining these medications, be aware of the following:

• CYP2D6 inhibition: Bupropion is a potent inhibitor of CYP2D6 and can increase sertraline blood levels 4
• Dose adjustments: May need to reduce sertraline dose when adding bupropion
• Monitoring: Close follow-up within 1-2 weeks of starting combination therapy is recommended 5

Potential Risks and Monitoring

Rare but serious risks:

• Serotonin syndrome: Although rare, cases have been reported with this combination 6
  • Monitor for: confusion, myoclonus, agitation, hyperthermia, autonomic instability
  • Discontinue both medications if suspected

Common side effects to monitor:

• Headache (common with both medications)
• Insomnia or sleep disturbances
• Gastrointestinal effects (nausea, diarrhea)
• Anxiety or restlessness
• Blood pressure changes

Practical Recommendations

1. Start low and titrate slowly:

   • If adding bupropion to existing sertraline: Begin with bupropion 150 mg daily
   • If adding sertraline to existing bupropion: Begin with sertraline 25-50 mg daily

2. Follow-up timing:

   • Schedule follow-up within 1-2 weeks of starting the combination 5
   • Continue regular monitoring during dose adjustments

3. Contraindications:

   • Do not combine with MAOIs (14-day washout period required) 4
   • Use caution in patients with seizure disorders or eating disorders
   • Use caution in patients taking other medications that lower seizure threshold 4

Special Considerations

• Seizure risk: Bupropion lowers seizure threshold; use caution in patients with risk factors
• Pregnancy: Risk-benefit assessment needed for each medication
• Discontinuation: Taper sertraline gradually to minimize withdrawal symptoms 5

This combination can be particularly beneficial for patients experiencing sexual side effects from sertraline or those with partial response to either medication alone, but requires careful monitoring and appropriate dose adjustments.