What is the best course of treatment for a patient with Obsessive-Compulsive Disorder (OCD) and Attention Deficit Hyperactivity Disorder (ADHD) currently taking Wellbutrin (Bupropion) XL 150 mg daily and Lisdexamfetamine (Vyvanse) 30 mg daily?

Treatment Approach for OCD in a Patient on Wellbutrin and Lisdexamfetamine

Your patient's current regimen is inadequate for OCD treatment—you must add a first-line SSRI or clomipramine, as neither bupropion nor lisdexamfetamine have evidence supporting efficacy for OCD.

Critical Problem: No OCD-Specific Treatment

• Bupropion (Wellbutrin) is not effective for OCD and may actually worsen symptoms—an open-label study showed that 8 of 12 patients experienced exacerbation of OCD symptoms with a mean 21% increase in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores 1

• Lisdexamfetamine is FDA-approved only for ADHD treatment and has no established role in OCD management 2

• Your patient essentially has untreated OCD despite being on two psychiatric medications

Recommended Treatment Algorithm

Step 1: Add First-Line OCD Pharmacotherapy

Initiate an SSRI immediately as the evidence-based first-line treatment for OCD:

• Start with sertraline, fluoxetine, fluvoxamine, paroxetine, or clomipramine (if SSRIs fail)
• OCD typically requires higher SSRI doses than depression and longer trial duration (10-12 weeks minimum)
• Continue the lisdexamfetamine 30 mg daily for ADHD management 2

Step 2: Address the Bupropion

Consider discontinuing or maintaining bupropion based on specific indication:

• If prescribed solely for ADHD augmentation: discontinue it—bupropion showed only modest benefit for ADHD (standardized mean difference -0.50) and is not first-line therapy 3
• If prescribed for comorbid depression: maintain it while adding the SSRI, monitoring for serotonin syndrome
• Bupropion has low-quality evidence for ADHD benefit and demonstrated harm in OCD 3, 1

Step 3: Optimize ADHD Treatment if Needed

The lisdexamfetamine 30 mg dose may be subtherapeutic:

• Maximum approved dose is 70 mg daily 2
• Consider titrating upward if ADHD symptoms remain inadequately controlled after addressing OCD
• Lisdexamfetamine has superior efficacy to bupropion for ADHD and should be the primary ADHD agent 4

Important Safety Considerations

Drug Interaction Monitoring

• Bupropion lowers seizure threshold—this risk increases with doses above 450 mg/day and when combined with other medications 4
• Monitor for serotonergic effects if combining bupropion with an SSRI (though risk is lower than with other combinations)
• Stimulants like lisdexamfetamine can increase blood pressure and heart rate—monitor cardiovascular parameters 4

Psychiatric Comorbidity Management

• The combination of OCD and ADHD is common and requires treating both conditions adequately 4
• Untreated OCD significantly impairs quality of life and functioning—this is your priority outcome
• SSRIs do not worsen ADHD symptoms and are safe to combine with stimulants

Clinical Pitfalls to Avoid

Do not continue bupropion monotherapy expecting OCD improvement—the evidence shows potential harm rather than benefit 1

Do not delay SSRI initiation—OCD requires specific serotonergic treatment, and neither current medication addresses this

Do not undertitrate the SSRI—OCD typically requires maximum or near-maximum FDA-approved doses for adequate response

Do not assess treatment response too early—allow 10-12 weeks at therapeutic SSRI doses before concluding treatment failure

Monitoring Plan

• Assess OCD symptoms using YBOCS at baseline and every 4 weeks 1
• Monitor ADHD symptoms with validated rating scales (e.g., CAARS) 5
• Check blood pressure and pulse regularly given stimulant use 4
• Screen for emerging suicidality, particularly when initiating SSRI therapy 4
• Evaluate for medication adherence at each visit, as this is a common problem in ADHD treatment 4