Is Wellbutrin (bupropion) useful for treating anxiety disorders?

Is Wellbutrin Helpful for Anxiety?

Bupropion (Wellbutrin) should generally be avoided as a first-line treatment for anxiety disorders and is specifically contraindicated in patients with agitated depression or prominent anxiety symptoms. 1, 2

Primary Evidence Against Use in Anxiety

The American Academy of Family Physicians explicitly states that bupropion "should not be used in agitated patients" due to its activating properties. 1 This recommendation is reinforced by clinical trial data showing SSRIs demonstrate superior efficacy compared to bupropion specifically in anxious depression, with a 6% absolute difference in response rates (65.4% vs 59.4%, p=0.03). 3

When Bupropion May Be Considered

Bupropion can be appropriate for anxiety only when it occurs as part of a depressive syndrome with prominent apathy, fatigue, or low energy. 2 The key clinical scenario is:

• Depression with comorbid anxiety where the patient also exhibits significant apathy or lack of energy 2
• Patients attempting smoking cessation or reducing alcohol intake who also have depression and anxiety 2
• Patients who cannot tolerate SSRIs due to sexual dysfunction or weight gain concerns 4

Critical Monitoring Requirements

If bupropion is initiated in a patient with any anxiety symptoms, the American College of Physicians mandates assessment within 1-2 weeks specifically monitoring for emergence of agitation, irritability, anxiety, or unusual behavioral changes. 2 The second daily dose must be taken before 3 PM to minimize insomnia, which can exacerbate anxiety. 1, 2

Comparative Efficacy Data

When directly compared in patients with anxious depression (defined as HAM-D anxiety-somatization factor ≥7), SSRIs showed:

• Greater HAM-D response rates (65.4% vs 59.4%, p=0.03) 3
• Greater Hamilton Anxiety Scale response rates (61.5% vs 54.5%, p=0.03) 3
• Number-needed-to-treat of 17, meaning 17 patients would need SSRI treatment instead of bupropion to obtain one additional responder 3

Mechanism Explaining Anxiogenic Effects

Bupropion's mechanism as a norepinephrine and dopamine reuptake inhibitor with no serotonergic activity explains its potential to provoke anxiety, particularly at higher doses. 5, 6 The 2025 review confirms its "stimulating properties can provoke anxiety" and recommends a "cautious approach" with lower initial doses. 5

Absolute Contraindications

Never use bupropion in patients with: 1, 2

• Seizure disorders (lowers seizure threshold)
• Anorexia or bulimia nervosa
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs
• Uncontrolled hypertension
• Current MAOI use or within 14 days of discontinuation

Clinical Decision Algorithm

1. If primary anxiety disorder without depression: Do not use bupropion—choose SSRI/SNRI 1, 3
2. If depression with severe anxiety: Prefer SSRI over bupropion 3
3. If depression with mild-moderate anxiety plus apathy/fatigue: Consider bupropion with close monitoring 2
4. If inadequate response after 6-8 weeks: Switch rather than continue ineffective therapy 2

The psychiatrist survey data reveals that clinicians already avoid prescribing bupropion when comorbid anxiety disorders or activation symptoms are present, despite its advantages for sexual dysfunction and weight gain. 4 This clinical practice pattern aligns with the evidence showing modest but statistically significant superiority of SSRIs in anxious depression. 3