Is Wellbutrin (bupropion) effective for treating anxiety disorders?

Bupropion for Anxiety: Not Recommended

Bupropion should generally be avoided for treating anxiety disorders and is not FDA-approved for this indication, as its activating norepinephrine-dopamine mechanism can provoke or worsen anxiety symptoms, particularly in patients with severe anxiety or panic disorder. 1

Why Bupropion Is Problematic for Anxiety

• Bupropion is a norepinephrine and dopamine reuptake inhibitor with stimulating properties that fundamentally differ from serotonergic agents (SSRIs/SNRIs) that are standard first-line treatments for anxiety disorders 1
• Common side effects include nervousness, insomnia, and anxiety itself, making it inherently anxiogenic in many patients 2
• Clinical guidelines explicitly warn that "bupropion is activating and can exacerbate anxiety" 3
• The Japanese Society of Anxiety and Related Disorders guidelines recommend SSRIs (escitalopram, sertraline, paroxetine, fluvoxamine) and SNRIs (venlafaxine) as standard pharmacotherapy for social anxiety disorder, with no mention of bupropion 3

Evidence in Depression with Comorbid Anxiety

The picture becomes more nuanced when depression is the primary diagnosis with accompanying anxiety symptoms:

• For anxious depression specifically, SSRIs demonstrate modest superiority over bupropion, with response rates of 65.4% versus 59.4% (p=0.03), requiring treatment of 17 patients with an SSRI rather than bupropion to obtain one additional responder 4
• However, multiple head-to-head trials show similar overall antidepressant efficacy between bupropion and SSRIs when treating major depressive disorder with anxiety symptoms 1
• A recent naturalistic 12-week study using propensity matching found no significant difference in anxiety outcomes between SSRI and bupropion groups, with both improving comparably over time 5

Clinical Decision Algorithm

For primary anxiety disorders (GAD, social anxiety, panic disorder):

• Do NOT use bupropion 1
• Start with SSRIs (escitalopram, sertraline) or SNRIs (venlafaxine) as first-line 3

For major depression with severe anxiety:

• Prefer SSRIs over bupropion due to modest efficacy advantage 4
• Consider venlafaxine, which may be superior to fluoxetine specifically for anxiety symptoms 1

For major depression with mild-to-moderate anxiety where sexual dysfunction is a major concern:

• Bupropion may be cautiously considered, as it has the lowest rate of sexual adverse events among antidepressants 3, 1
• Start at 150 mg/day and monitor closely for anxiety worsening before titration 1
• Discontinue immediately if anxiety significantly worsens 1

For major depression with minimal anxiety:

• Bupropion is appropriate and shows no efficacy difference compared to SSRIs 4

Critical Contraindications

Absolutely avoid bupropion in patients with:

• Primary anxiety disorders without depression 1
• Severe anxiety or panic disorder 1
• History of seizures or conditions lowering seizure threshold (0.1% seizure risk) 3
• History of anxiety exacerbation on activating medications 1

Common Pitfall

The most frequent error is prescribing bupropion to patients presenting with mixed anxiety-depression symptoms without carefully assessing which is primary. If anxiety is the predominant or equally severe symptom, choose an SSRI/SNRI first. Only consider bupropion when depression clearly predominates and anxiety is mild, or when SSRI side effects (particularly sexual dysfunction) are intolerable. 1, 4