Bupropion for Anxiety: Not Recommended as Primary Treatment
Bupropion is not FDA-approved for anxiety disorders and should not be used as a first-line treatment for primary anxiety, though it may be appropriate for patients with comorbid depression and mild-to-moderate anxiety symptoms. 1
Evidence Against Primary Use in Anxiety
Bupropion functions as a norepinephrine and dopamine reuptake inhibitor with no serotonergic activity, which is the primary mechanism through which most anxiolytics work. 2, 3 This fundamental pharmacologic profile makes it mechanistically less suited for anxiety treatment compared to SSRIs or SNRIs.
The drug's stimulating properties can actually provoke or worsen anxiety, particularly at higher doses, due to its activating effects on noradrenergic and dopaminergic systems. 1, 2 This anxiogenic potential is a well-recognized clinical concern that has persisted throughout its use.
Limited Evidence for Anxiolytic Effects
While one small pilot trial (n=24) showed bupropion XL (150-300 mg/day) had comparable anxiolytic efficacy to escitalopram in generalized anxiety disorder over 12 weeks, this single study is insufficient to establish efficacy. 4 The trial was underpowered and requires replication before drawing definitive conclusions.
A naturalistic study (n=8,457) using propensity matching found no significant difference in anxiety outcomes between bupropion and SSRI groups over 12 weeks, with both groups improving comparably. 5 However, this observational design cannot establish equivalence for primary anxiety treatment.
When Bupropion May Be Considered
Bupropion may reduce anxiety symptoms in patients with primary depression and comorbid mild-to-moderate anxiety, showing comparable efficacy to SSRIs and SNRIs in this specific population. 1 Clinical trials suggest it can address both conditions simultaneously through complementary noradrenergic/dopaminergic mechanisms. 2, 6
Interestingly, one smoking cessation study found that patients with higher baseline anxiety scores responded better to bupropion at 3 and 6 months (p=0.0052 and p=0.017 respectively), suggesting anxiety may predict positive response in certain contexts. 7
Critical Prescribing Caveats
If bupropion is used in patients with any anxiety symptoms:
- Start at lower doses (37.5-75 mg daily) and titrate slowly by 37.5 mg every 3 days to minimize anxiogenic effects. 8
- Monitor closely for increased agitation or worsening anxiety, as bupropion is an activating medication. 6
- Administer the first dose in the morning and any second dose before 3 PM to prevent insomnia, which can exacerbate anxiety. 8
- Avoid in patients with severe anxiety or panic disorder, where SSRIs remain the evidence-based first-line treatment. 1
Absolute Contraindications
Never use bupropion in patients with seizure disorders, eating disorders (bulimia/anorexia), or those at elevated seizure risk, as it lowers seizure threshold with a 0.1% documented risk. 9, 2 Avoid concurrent MAOI use or within 14 days of MAOI discontinuation due to hypertensive crisis risk. 2, 6
Bottom Line Algorithm
For primary anxiety disorders: Use SSRIs or SNRIs as first-line treatment, not bupropion. 1
For depression with comorbid mild-to-moderate anxiety: Bupropion is a reasonable option, particularly if the patient also wants to quit smoking or has concerns about sexual dysfunction or weight gain common with SSRIs. 2, 1
For severe depression with anxious distress: SSRIs may be preferable to bupropion. 1