My obsessive‑compulsive disorder has worsened after starting Wellbutrin (bupropion) for depression; what should I do?

Discontinue Wellbutrin Immediately and Switch to Evidence-Based OCD Treatment

Stop bupropion (Wellbutrin) now—it worsens OCD symptoms in the majority of patients and has no therapeutic role in OCD management. 1

Why Wellbutrin Worsens OCD

• Bupropion exacerbates OCD symptoms in approximately 67% of patients, with a mean 21% increase in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores in those who deteriorate. 1
• The mechanism involves dopamine dysregulation—bupropion inhibits dopamine reuptake, and dopamine appears to worsen obsessive-compulsive symptoms in most individuals. 1
• Only 2 of 12 patients (17%) showed any improvement in a controlled trial, while 8 patients experienced symptom exacerbation. 1
• Bupropion is definitively not an effective treatment for OCD and should be avoided in patients with this condition. 1

Immediate Action Plan

Step 1: Discontinue Bupropion

• Taper off bupropion over 1-2 weeks to avoid discontinuation symptoms (though it has minimal withdrawal compared to SSRIs). 2
• Monitor for initial worsening before improvement as the dopaminergic effects resolve.

Step 2: Initiate First-Line OCD Treatment

For the depression component, you need an SSRI at OCD-specific doses (higher than typical antidepressant doses):

• Start an SSRI immediately: Fluoxetine 60-80 mg daily, paroxetine 60 mg daily, sertraline 200 mg daily, or fluvoxamine 300 mg daily. 3
• SSRIs are the only medications proven effective for OCD in multisite randomized controlled trials. 4
• Higher doses are required for OCD than for depression—this is a critical distinction that prevents treatment failure. 3
• Allow 8-12 weeks at maximum tolerated dose before declaring treatment failure; clinically significant improvement typically appears by week 6. 5

Number needed to treat (NNT) for SSRIs in OCD is 5, compared to NNT of 3 for cognitive-behavioral therapy. 5

Step 3: Add Cognitive-Behavioral Therapy with ERP

• CBT with exposure and response prevention (ERP) is the psychological treatment of choice and has larger effect sizes than pharmacotherapy alone (NNT 3 vs 5). 3, 5
• Plan for 10-20 sessions of ERP, either individual or group format. 3, 5
• Between-session homework adherence is the strongest predictor of good outcomes—this means practicing ERP exercises at home between therapy sessions. 3, 5
• Combined SSRI plus CBT/ERP produces optimal outcomes and is superior to either treatment alone. 5

Critical Monitoring in First 6 Weeks

• Watch closely for behavioral activation, akathisia, or suicidal ideation when starting the SSRI, particularly in patients under age 24 (FDA boxed warning). 5
• Common SSRI side effects include initial gastrointestinal symptoms, sexual dysfunction, and insomnia—assess these carefully when titrating to therapeutic doses. 3

If Inadequate Response After 12 Weeks

• Consider aripiprazole augmentation (5-20 mg daily), which has the strongest evidence for SSRI-resistant OCD. 5, 6
• Glutamatergic agents (N-acetylcysteine, memantine) have evidence for augmentation in treatment-resistant cases. 5, 6
• Do not discontinue the SSRI prematurely—maintain treatment for minimum 8-12 weeks at maximum dose before declaring failure. 5

Long-Term Management

• Plan for 12-24 months of maintenance therapy after achieving remission, as this reduces relapse risk in up to 67% of OCD patients. 5
• Continue CBT/ERP homework exercises even after symptom improvement to maintain gains. 3
• Address any family accommodation behaviors (family members enabling compulsions) through psychoeducation, as these maintain OCD symptoms. 5

Key Pitfall to Avoid

The most common error is using antidepressant doses of SSRIs for OCD rather than the higher OCD-specific doses required. This leads to treatment failure and unnecessary medication switching. 3 Ensure your prescriber understands that OCD requires higher SSRI doses than depression or other anxiety disorders.