What alternative treatment options are available for a patient with obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) who has a history of not tolerating bupropion and Viibryd (vilazodone), and has a GeneSight report indicating that escitalopram is also not recommended?

Alternative Treatment Options When Escitalopram is Contraindicated by GeneSight

When escitalopram appears in the "red zone" on a GeneSight report for a patient with OCD and ADHD who has already failed bupropion and vilazodone, sertraline should be your first-line SSRI choice for OCD treatment, combined with cognitive-behavioral therapy (CBT) with exposure and response prevention (ERP), while addressing ADHD separately with stimulant medication. 1, 2

Treatment Algorithm for OCD

First-Line Approach for OCD

• Sertraline is FDA-approved for OCD treatment and has demonstrated efficacy in 12-week trials with obsessive-compulsive outpatients, making it an excellent alternative when escitalopram is contraindicated 2

• Start sertraline at 50 mg daily and titrate to maximum recommended or tolerated dose (typically 150-200 mg daily for OCD, which requires higher doses than depression) over at least 8 weeks 1, 2

• Combine sertraline with CBT consisting of patient and family psychoeducation and ERP for 10-20 sessions, as this combination shows superior outcomes compared to medication alone 1

Alternative SSRI Options

• Fluvoxamine, paroxetine, or fluoxetine are additional SSRI alternatives if sertraline is not tolerated, as all SSRIs have similar effect sizes for OCD treatment 1

• No significant differences exist between SSRIs in efficacy for treating OCD, so the choice should be based on side effect profile, drug interactions, and past SSRI use 1

If SSRIs Fail

• Switch to clomipramine (a tricyclic antidepressant) if two adequate SSRI trials fail, as it remains highly effective for treatment-resistant OCD 1

• Consider combination therapy with clomipramine plus an SSRI for severe, treatment-resistant cases, though this requires careful monitoring of electrocardiograms, blood levels, and vital signs due to drug interactions and cardiovascular risks including QTc prolongation and tachycardia 3

• Augmentation with atypical antipsychotics can be considered after failed SSRI trials 1

Treatment Algorithm for ADHD

First-Line Stimulant Therapy

• Initiate stimulant medication (methylphenidate or amphetamines) as first-line treatment for ADHD, as these have 70-80% response rates and the largest effect sizes from over 161 randomized controlled trials 4

• Methylphenidate dosing: 5-20 mg three times daily for adults, or use extended-release formulations for once-daily dosing with maximum daily dose of 60 mg 4

• Dextroamphetamine dosing: 5 mg three times daily to 20 mg twice daily for adults 1

• Long-acting formulations provide around-the-clock effects and reduce rebound symptoms, improving medication adherence 4

Non-Stimulant Alternatives

• Atomoxetine (60-100 mg daily) is the only FDA-approved non-stimulant for adult ADHD and should be considered if stimulants are contraindicated or not tolerated, though it requires 2-4 weeks to achieve full effect 4

• Guanfacine (1-4 mg daily) or clonidine are FDA-approved alternatives, particularly useful when sleep disturbances, tics, or disruptive behavior disorders are present 4

Critical Considerations

Why Not Bupropion Again?

• Bupropion is explicitly positioned as a second-line agent for ADHD with smaller effect sizes than stimulants, and since the patient already failed bupropion, retrial is unlikely to be beneficial 4, 5, 6

• Bupropion has no proven efficacy for OCD and should not be considered for this indication 6

Addressing Both Conditions

• Treat ADHD with stimulants first, as rapid response (within days) allows quick assessment of whether ADHD symptom improvement indirectly reduces OCD-related functional impairment 4

• If ADHD symptoms improve but OCD symptoms persist, add sertraline to the stimulant regimen, as there are no significant drug-drug interactions between stimulants and SSRIs 4

• SSRIs remain the treatment of choice for OCD and are weight-neutral with long-term use, and can be safely combined with stimulants 4

Common Pitfalls to Avoid

• Do not assume a single medication will treat both ADHD and OCD effectively, as no antidepressant has proven efficacy for this dual purpose 4

• Do not use MAO inhibitors concurrently with stimulants or bupropion due to risk of hypertensive crisis; at least 14 days should elapse between discontinuation of an MAOI and initiation of these medications 4

• Monitor for cardiovascular side effects when combining medications, particularly if considering clomipramine plus SSRI combination therapy for severe OCD 3

• Ensure adequate trial duration and dosing - OCD requires at least 8 weeks at maximum tolerated SSRI dose before declaring treatment failure 1

Monitoring Requirements

• Schedule follow-up in 2-4 weeks initially to assess medication tolerability and early response 7

• Monitor blood pressure and pulse at baseline and regularly during stimulant treatment 4

• Track OCD symptom severity using standardized scales (such as Yale-Brown Obsessive Compulsive Scale) at baseline and throughout treatment 1

• Maintain SSRI treatment for at least 12-24 months after achieving remission to prevent OCD relapse 1, 7