What is a suitable adjunct to Wellbutrin (bupropion) for treating anxiety?

Adjunct Medications to Bupropion for Anxiety

For patients taking bupropion (Wellbutrin) who need additional treatment for anxiety, buspirone (BuSpar) is the most appropriate first-line adjunct medication due to its efficacy for mild to moderate anxiety with minimal drug interactions and favorable side effect profile. 1

First-Line Options

Buspirone (BuSpar)

• Dosing: Start at 5mg twice daily, can increase up to maximum of 20mg three times daily
• Mechanism: Non-benzodiazepine anxiolytic that works through serotonin 5-HT1A receptors
• Benefits:
  • Specifically indicated for mild to moderate anxiety 1
  • No significant drug interactions with bupropion
  • No risk of dependence or withdrawal
  • Does not cause sedation or cognitive impairment
• Limitations:
  • May take 2-4 weeks to become effective
  • Less effective for severe anxiety

SSRIs

SSRIs can be considered when anxiety symptoms are moderate to severe:

• Sertraline (Zoloft): 25-50mg daily initially, up to 200mg daily

  • Well-tolerated with less effect on metabolism of other medications 1
  • Less likely to cause drug interactions with bupropion

• Escitalopram/Citalopram: 10mg daily initially, up to 40mg daily

  • Well-tolerated with minimal side effects 1
  • Recent evidence shows comparable anxiolytic efficacy to bupropion 2

Second-Line Options

SNRIs

• Venlafaxine: 37.5mg daily initially, up to 225mg daily 3
  • Effective for generalized anxiety disorder
  • Monitor for blood pressure increases when combined with bupropion

Mirtazapine (Remeron)

• Dosing: 7.5mg at bedtime initially, up to 30mg at bedtime
• Benefits:
  • Promotes sleep and appetite 1
  • Complementary to bupropion's activating effects
  • Potent and well-tolerated

Important Considerations

Medication Selection Algorithm

1. Assess anxiety severity:

   • For mild to moderate anxiety → Buspirone
   • For moderate to severe anxiety → SSRI (preferably sertraline)
   • For anxiety with insomnia → Mirtazapine

2. Consider contraindications:

   • Avoid benzodiazepines in patients with substance use histories 3
   • Use caution with SNRIs in patients with cardiovascular disease

3. Monitor for effectiveness:

   • Allow 2-4 weeks for buspirone to take effect
   • Allow 4-8 weeks for full therapeutic trial of antidepressants 1
   • Use standardized scales like GAD-7 to track progress 3

Important Cautions

• Avoid benzodiazepines as first-line treatment due to risk of dependence and potential for disinhibition, especially in younger patients 1
• Avoid antipsychotics as first-line adjuncts unless there are psychotic symptoms or treatment-resistant anxiety 4
• Bupropion itself is not anxiety-inducing despite common clinical belief - recent large-scale studies show comparable anxiety outcomes between bupropion and SSRIs over 12 weeks of treatment 5
• Baseline anxiety levels do not appear to predict differential response to bupropion versus sertraline 6

Monitoring

• Assess response after 4-8 weeks of treatment
• If inadequate response to first adjunct medication:
  1. Optimize dose of current adjunct medication
  2. Switch to alternative adjunct medication
  3. Consider combination therapy with psychotherapy (CBT) 3

Special Populations

• Bipolar disorder: Avoid antidepressant monotherapy; consult psychiatry for mood stabilizer options 3
• Older adults: Start with lower doses of SSRIs 3
• Cardiovascular disease: Use caution with SNRIs; start at lower doses and titrate slowly 3

Remember that bupropion should not be used in agitated patients or those with seizure disorders, and to minimize insomnia risk, the second dose should be given before 3 PM 1.