Bupropion is Not Effective for OCD and May Worsen Symptoms
Bupropion should not be used to treat obsessive-compulsive disorder, as it has demonstrated no efficacy and may actually exacerbate OCD symptoms in a majority of patients. 1
Evidence Against Bupropion for OCD
The only clinical trial examining bupropion for OCD showed concerning results:
In an 8-week open-label trial of bupropion (up to 300 mg daily) in 12 OCD patients, the medication had no mean effect on symptoms, with an average Yale-Brown Obsessive Compulsive Scale (YBOCS) decrease of only 1.1 points. 1
More alarmingly, 8 out of 12 patients (67%) experienced worsening of their OCD symptoms, with a mean YBOCS increase of 21%. 1
Only 4 patients showed improvement, and merely 2 met responder criteria (≥25% YBOCS reduction). 1
Established First-Line Treatments for OCD
Instead of bupropion, the evidence-based treatment algorithm for OCD is clear:
First-line pharmacological treatment consists exclusively of serotonergic antidepressants:
Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment based on established efficacy, tolerability, safety, and absence of abuse potential. 2
SSRIs require higher doses for OCD than for depression—typically fluoxetine 60-80 mg daily or paroxetine 60 mg daily. 3
Clomipramine (a serotonergic tricyclic antidepressant) is also effective but associated with more adverse effects. 4, 5
Cognitive-Behavioral Therapy with Exposure and Response Prevention (CBT with ERP) is the psychological treatment of choice, with superior effect sizes compared to medication (number needed to treat of 3 for CBT vs 5 for SSRIs). 2
Why Only Serotonergic Agents Work
The only medications proven effective for OCD in multisite randomized controlled trials are serotonin reuptake inhibitors. 5, 6
Other antidepressants, including bupropion (which works primarily through dopamine and norepinephrine mechanisms), are either less effective or insufficiently studied. 4
Treatment duration of at least 12-24 months is recommended after achieving remission due to high relapse risk. 3
Treatment Algorithm for OCD
Step 1: SSRI monotherapy at high doses OR CBT with ERP (or combination). 2
Step 2 (if inadequate response after 8-12 weeks): Optimize SSRI dose, switch to another SSRI or clomipramine, or add CBT if not already implemented. 2
Step 3 (treatment-resistant cases): Augmentation with atypical antipsychotics, glutamatergic agents (N-acetylcysteine, memantine), or clomipramine added to SSRI. 2, 6
Clinical Pitfall to Avoid
Do not prescribe bupropion for OCD under the assumption that it may help comorbid depression—the risk of worsening obsessive-compulsive symptoms outweighs any potential antidepressant benefit. 1 If depression coexists with OCD, use an SSRI at OCD-appropriate doses, which will address both conditions. 3