Bupropion Is Generally Not Appropriate for Primary Anxiety Disorders
Bupropion should be avoided as first-line treatment for anxiety disorders because its activating dopaminergic and noradrenergic properties can worsen anxiety symptoms, particularly in patients with prominent agitation. 1
When Bupropion May Be Considered for Anxiety
Bupropion can be appropriate in specific clinical contexts where anxiety occurs as part of a broader depressive syndrome:
Depression with Comorbid Anxiety
- When anxiety symptoms occur within major depressive disorder, bupropion demonstrates comparable anxiolytic efficacy to SSRIs and SNRIs. A meta-analysis of 2,890 patients across 10 randomized trials found no significant difference in anxiety reduction between bupropion and SSRIs using Hamilton Anxiety Scale scores (-8.8 vs -9.1, p=0.177). 2
- Baseline anxiety does not diminish bupropion's antidepressant efficacy. STAR*D trial analyses confirm that comorbid anxiety does not modify treatment response rates. 3
- Bupropion is particularly beneficial for depressed patients with prominent apathy, fatigue, or low energy who also have anxiety, as it addresses motivational deficits through dopamine and norepinephrine reuptake inhibition. 1
Dual-Benefit Scenarios
- For patients with depression, anxiety, and nicotine dependence, bupropion addresses all three conditions simultaneously, achieving 12-month smoking abstinence rates of 30.3% (or 35.5% when combined with nicotine replacement therapy). 3
- For patients with depression, anxiety, and alcohol dependence, combining bupropion with naltrexone provides complementary mechanisms without pharmacokinetic interactions. 3
Absolute Contraindications
Do not prescribe bupropion if any of the following are present:
- Seizure disorders or any condition predisposing to seizures (prior seizure, brain tumor, stroke, head trauma, eating disorders, abrupt alcohol/benzodiazepine withdrawal) – seizure risk is approximately 0.1% (1 in 1,000) at standard doses. 3, 4, 1
- Current or recent MAOI use (within 14 days of discontinuation). 3
- Uncontrolled hypertension, as bupropion elevates blood pressure and heart rate. 3, 1
- Prominent agitation or highly anxious presentation, as bupropion's activating properties will exacerbate these symptoms. 1
Practical Dosing Strategy to Minimize Anxiety
If bupropion is prescribed for depression with comorbid anxiety:
- Start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) if tolerated. 3
- Administer the second dose before 3 PM to minimize insomnia, which can worsen anxiety. 3, 1
- Monitor closely during weeks 1–2 for emergence of agitation, irritability, or worsening anxiety, especially in patients under age 24 who carry FDA black-box warning for suicidal ideation. 3
- Assess response at 6–8 weeks; if anxiety worsens or inadequate response occurs, switch to an SSRI rather than continuing ineffective therapy. 3, 1
Preferred First-Line Options for Primary Anxiety
For patients whose primary diagnosis is an anxiety disorder without significant depression, initiate an SSRI (escitalopram 10–20 mg daily or sertraline 50–200 mg daily) or SNRI instead of bupropion. 3, 1
Special Populations Requiring Dose Adjustment
- Moderate-to-severe renal impairment (eGFR <90 mL/min): Reduce total daily dose by 50% (e.g., 150 mg daily instead of 300 mg). 3, 1
- Moderate-to-severe hepatic impairment: Maximum dose 150 mg daily. 3, 1
- Older adults (>65 years): Start at 37.5 mg every morning, increase by 37.5 mg every 3 days as tolerated, with maximum 300 mg daily. 3
Common Pitfall to Avoid
Do not assume bupropion is "too activating" for all patients with anxiety. In controlled trials of depressed patients with mild-to-moderate anxiety, bupropion produced equivalent anxiety reduction compared to SSRIs, with no consistent difference in time to anxiolysis. 2 The key distinction is whether anxiety exists as a primary disorder (avoid bupropion) versus as a symptom of depression (bupropion is appropriate). 1, 5