Adding Medication to Wellbutrin for Anxiety
Add an SSRI (selective serotonin reuptake inhibitor) such as sertraline, escitalopram, or paroxetine to bupropion when treating anxiety, as SSRIs are first-line anxiolytic agents and can be safely combined with bupropion. 1
Rationale for SSRI Addition
SSRIs are the primary evidence-based pharmacotherapy for anxiety disorders in both adults and children/adolescents, with strong guideline support for generalized anxiety, social anxiety, separation anxiety, and panic disorder 1
Bupropion alone is not indicated for anxiety treatment and is specifically noted as "activating" and "should not be used in agitated patients" 1
Combination therapy is safe: Bupropion can be coadministered with SSRIs, though dose adjustments may be needed since bupropion inhibits CYP2D6, which metabolizes several SSRIs including sertraline, paroxetine, and fluoxetine 2
Specific SSRI Recommendations
Sertraline is an excellent first choice because:
- Well-tolerated with less effect on metabolism of other medications compared to other SSRIs 1
- Demonstrated comparable anxiolytic efficacy to bupropion in head-to-head trials for depression with anxiety 1
- Start at 25-50 mg daily, maximum 200 mg daily 1
Escitalopram is another strong option:
- Has the least effect on CYP450 isoenzymes, minimizing drug interactions with bupropion 1
- Start at 10 mg daily, maximum 40 mg daily 1
- Demonstrated comparable efficacy to bupropion in GAD 3
Paroxetine can be used but requires caution:
- More anticholinergic than other SSRIs 1
- Associated with discontinuation syndrome 1
- Start at 10 mg daily, maximum 40 mg daily 1
Dosing Considerations When Combining
- Start the SSRI at standard initial doses as bupropion's CYP2D6 inhibition may increase SSRI levels 2
- Monitor for serotonin syndrome when combining, though risk is low with SSRI + bupropion (higher risk occurs with MAOIs) 1
- Titrate SSRI slowly at 1-2 week intervals for shorter half-life agents (sertraline, escitalopram) 1
- Consider reducing SSRI dose by 25-50% if side effects emerge, as bupropion may increase SSRI exposure 2
Alternative: SNRI Addition
SNRIs (venlafaxine or duloxetine) are second-line options:
- Demonstrated efficacy for anxiety disorders in children and adolescents 1
- Venlafaxine showed superior anxiolytic effects compared to fluoxetine in some trials 1
- However, SNRIs are also metabolized by CYP2D6, requiring dose adjustment when combined with bupropion 2
What NOT to Add
Avoid buspirone as monotherapy augmentation:
- Takes 2-4 weeks to become effective and is only useful for mild-moderate agitation 1
- Less robust evidence base compared to SSRIs
Avoid benzodiazepines for chronic anxiety management:
- Not addressed in primary anxiety treatment guidelines as first-line 1
- Risk of dependence with chronic use
Common Pitfall to Avoid
Do not assume bupropion worsens anxiety and discontinue it prematurely. Recent naturalistic data over 12 weeks showed no difference in anxiety outcomes between SSRI and bupropion monotherapy when properly matched 4. Additionally, baseline anxiety levels did not predict differential response to bupropion versus sertraline 5, 6. The key is adding appropriate anxiolytic medication (SSRI) rather than stopping bupropion.