Bupropion for Anxiety: Clinical Recommendation
Bupropion can be used to treat anxiety, particularly in patients with comorbid depression and anxiety, as it demonstrates comparable anxiolytic efficacy to SSRIs with no significant difference in anxiety outcomes. 1, 2
Evidence-Based Rationale
Primary Indication Context
- Bupropion is FDA-approved for major depressive disorder and smoking cessation, not specifically for anxiety disorders 3
- However, the American College of Physicians recognizes bupropion as effective for depression treatment with efficacy comparable to other antidepressants, including in patients with comorbid anxiety 4, 5
Anxiolytic Efficacy Data
Direct comparison studies demonstrate bupropion's anxiety-reducing properties:
- A meta-analysis of 2,890 patients showed bupropion and SSRIs produced identical improvement in anxiety symptoms using Hamilton Anxiety Scale scores (-8.8 vs. -9.1, p=0.177) 2
- A 12-week naturalistic study of 8,457 patients using propensity matching found no differences in anxiety outcomes between bupropion and SSRI groups, with both improving comparably over time 1
- A controlled trial directly comparing bupropion XL (150-300 mg/day) to escitalopram (10-20 mg/day) in generalized anxiety disorder patients showed comparable anxiolytic efficacy 6
- Placebo-controlled trials demonstrated 60-70% response rates for both depression and anxiety symptoms, with superiority over placebo on Hamilton Anxiety Rating Scales 7
Clinical Nuances and Caveats
The stimulating properties of bupropion require careful dosing:
- Start at lower doses and titrate gradually to minimize potential anxiogenic effects, which can occur particularly at higher doses 3
- The American College of Physicians recommends taking the second daily dose before 3 PM to minimize insomnia risk 5
- Maximum dose should not exceed 450 mg/day to minimize seizure risk 8
Bupropion shows particular advantages in specific anxiety presentations:
- Most effective for anxiety symptoms occurring in the context of major depressive disorder with apathy and low energy, given its beneficial dopaminergic effects 5
- The American College of Physicians found no effect of comorbid anxiety on comparative efficacy when bupropion was used as either first-step or second-step treatment for depression 4
Contraindications and Safety Monitoring
Absolute contraindications include: 5, 8
- History of seizure disorders (bupropion lowers seizure threshold)
- Eating disorders (anorexia nervosa, bulimia)
- Current or recent (within 14 days) MOAI use
- Uncontrolled hypertension
Required monitoring parameters: 5, 8
- Blood pressure, especially at treatment initiation
- Mood changes and suicidal ideation
- Seizure precursors (particularly if risk factors present)
Dose Adjustments for Special Populations
Renal impairment: 5
- Moderate to severe: reduce total daily dose to 150 mg/day
- End-stage renal disease: avoid use
Hepatic impairment: 5
- Moderate to severe: do not exceed 150 mg total daily dose
When to Consider Alternative or Combination Therapy
If anxiety persists or worsens on bupropion monotherapy:
- The American College of Physicians recommends SSRIs (particularly sertraline) as preferred add-on therapy for patients on bupropion experiencing persistent anxiety 8
- SNRIs (venlafaxine or duloxetine) represent strong alternatives, particularly if SSRIs are ineffective or not tolerated 8
- Evaluate response after 12 weeks of treatment and consider medication change if no significant improvement 5
Avoid benzodiazepines in combination with bupropion due to increased seizure risk if discontinued abruptly 8