Is Wellbutrin (bupropion) a suitable treatment option for a patient with anxiety, considering their medical history and potential contraindications?

Bupropion for Anxiety: Not Recommended as First-Line Treatment

Bupropion is not FDA-approved for anxiety disorders and should generally be avoided as monotherapy for primary anxiety, though it can be used cautiously in patients with comorbid depression and anxiety, particularly when apathy and low energy are prominent features. 1

FDA Indications and Warnings

Bupropion is FDA-approved only for major depressive disorder and smoking cessation—not for anxiety disorders. 1 The FDA label explicitly warns that patients and caregivers must monitor for "emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness)" especially early in treatment, as these symptoms may emerge or worsen. 1

Common adverse reactions occurring in ≥5% of patients at twice the placebo rate include agitation, anxiety, insomnia, and palpitations at the 400 mg/day dose. 1

When Bupropion May Be Appropriate for Anxiety

Use bupropion only when anxiety occurs as part of a depressive syndrome, not as a primary anxiety disorder. 2

The American Academy of Family Physicians recommends bupropion specifically for patients with depression and comorbid anxiety who also have:

• Prominent apathy, fatigue, or low energy (bupropion's dopaminergic effects target these symptoms) 2
• Concurrent smoking cessation needs 2
• Desire to reduce alcohol intake 2

Evidence on Anxiolytic vs. Anxiogenic Effects

The evidence reveals a nuanced picture:

For anxious depression: A pooled analysis of 10 studies (N=2,122) found SSRIs modestly superior to bupropion for major depression with high anxiety levels (HAM-D anxiety-somatization factor ≥7). SSRI response rates were 65.4% vs. 59.4% for bupropion (p=0.03), with a number-needed-to-treat of 17—meaning 17 patients would need SSRI treatment instead of bupropion to achieve one additional responder. 3

For mild-to-moderate anxiety in depression: A 1983 placebo-controlled trial showed bupropion significantly reduced Hamilton Anxiety Scale scores compared to placebo (p<0.01) in hospitalized depressed patients. 4 A 2023 naturalistic study (N=8,457) using propensity matching found no difference in anxiety outcomes between SSRI and bupropion groups over 12 weeks—both improved comparably. 5

Clinical reality: A 2025 review concluded that while bupropion may reduce anxiety in depressed patients with mild-to-moderate anxiety, its stimulating properties can provoke anxiety, particularly at higher doses. 6

Practical Implementation Algorithm

Step 1: Patient Selection

• Use bupropion ONLY if depression is the primary diagnosis with comorbid anxiety 2
• Confirm prominent apathy, fatigue, or low energy symptoms 2
• Screen for absolute contraindications 2, 1:
  • Seizure disorders or conditions lowering seizure threshold
  • Anorexia or bulimia nervosa
  • Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptics
  • Uncontrolled hypertension
  • Current MAOI use or within 14 days of discontinuation
  • Anatomically narrow angles (angle-closure glaucoma risk)

Step 2: Initiation Strategy to Minimize Anxiety

• Start at 150 mg once daily (not the standard 150 mg twice daily) 2
• Take second dose before 3 PM if advancing to twice daily to minimize insomnia 2
• Assess within 1-2 weeks for emergence of agitation, irritability, anxiety, or unusual behavioral changes 2

Step 3: Monitoring and Adjustment

• Monitor blood pressure, especially at treatment initiation 1
• Evaluate response at 6-8 weeks; if inadequate or anxiety worsens, switch medications rather than continuing ineffective therapy 2
• Maximum dose 300 mg/day; avoid 400 mg/day dose which has higher anxiety/agitation rates 1

Step 4: Dose Adjustments for Special Populations

• Moderate-to-severe renal impairment: reduce to 150 mg/day total 2
• Moderate-to-severe hepatic impairment: do not exceed 150 mg/day total 2

Critical Pitfalls to Avoid

Do not use bupropion for:

• Primary anxiety disorders (generalized anxiety disorder, panic disorder, social anxiety disorder) without comorbid depression 2, 6
• Severe depression with prominent anxious distress—SSRIs are preferable 3
• Patients with eating disorders due to seizure risk 2, 1

Common mistake: Prescribing bupropion at standard antidepressant doses (300 mg/day) immediately in anxious patients. This increases anxiogenic effects. Start lower and titrate based on tolerability. 2

Alternative Recommendation

For patients with primary anxiety or severe anxious depression, select an SSRI or SNRI as first-line treatment. 7, 3 Bupropion has lower rates of sexual adverse events compared to SSRIs, which may improve quality of life if the medication is tolerated, but this benefit is secondary to achieving anxiety control. 2