How long should a patient wait to add 100 SR Wellbutrin (Bupropion) to their Strattera (Atomoxetine) regimen, given 16 days at 60 mg with nausea and persistent fatigue as an intermediate metabolizer?

Timing of Wellbutrin Addition to Strattera Regimen

You should address the nausea and fatigue symptoms before adding Wellbutrin, rather than adding it immediately at 16 days. The nausea that emerged in the past 3 days is likely related to Strattera (atomoxetine) and requires management first, while the persistent fatigue may benefit from Wellbutrin addition once gastrointestinal symptoms are controlled.

Immediate Management of Current Symptoms

Address Nausea First

• Nausea is a common adverse effect of atomoxetine that typically emerges early in treatment and often resolves with continued use or dose adjustment 1
• As an intermediate CYP2D6 metabolizer, this patient has greater exposure to atomoxetine than extensive metabolizers, increasing the likelihood of adverse effects 1
• Manage the nausea with dopamine receptor antagonists (metoclopramide, prochlorperazine) or consider dose reduction of Strattera if nausea persists beyond one week 2
• If nausea persists despite antiemetic therapy for longer than a week, reassess the atomoxetine dose or consider alternative strategies 2

Evaluate Fatigue Etiology

• The persistent fatigue at lower Strattera doses suggests this may not be medication-induced but rather a residual symptom requiring additional treatment 3
• Atomoxetine augmentation with other agents has shown efficacy for residual fatigue in depression, with significant improvement in fatigue scores after 4-10 weeks of combination therapy 3

Timing for Wellbutrin Addition

Wait for Gastrointestinal Stabilization

• Do not add Wellbutrin until the nausea has resolved or been adequately controlled for at least 3-7 days 2
• This waiting period allows you to distinguish between atomoxetine-related nausea and any potential nausea from bupropion addition
• Bupropion itself can cause nausea in 6.7% of patients, which would compound the current problem 4

Optimal Initiation Strategy for Wellbutrin SR 100mg

• Start with 100mg SR once daily in the morning, not twice daily, to minimize adverse effects when combining with atomoxetine 5
• The standard titration for bupropion SR is 150mg once daily for 3 days, then 150mg twice daily, but starting at 100mg is appropriate given the polypharmacy context 5
• Administer the dose before 3 PM to minimize insomnia risk, which is already a potential issue with atomoxetine 5, 1

Monitoring After Addition

• Assess for therapeutic response and adverse effects within 1-2 weeks of adding bupropion 5
• Monitor specifically for increased agitation, as bupropion has activating properties that may be additive with atomoxetine 5
• Allow 6-8 weeks at an adequate combined dose before determining treatment response for fatigue 5

Clinical Rationale for This Approach

Pharmacological Considerations

• Both medications affect noradrenergic neurotransmission, which could theoretically be synergistic for fatigue but also increases the risk of adverse effects 1, 3
• Bupropion has shown efficacy for cancer-related fatigue with significant improvement in FACIT-F scores after 4 weeks at 150mg daily 6
• The combination addresses fatigue through complementary mechanisms: atomoxetine via selective norepinephrine reuptake inhibition and bupropion via noradrenergic/dopaminergic pathways 5, 1

Safety Considerations

• As an intermediate CYP2D6 metabolizer, this patient has slower elimination of atomoxetine, requiring more cautious addition of other medications 1
• The 100mg SR dose of bupropion is below the standard 150mg twice daily (300mg total) used for depression or smoking cessation, providing a safety margin 5
• Monitor blood pressure and heart rate, as both medications can cause elevations 5, 1

Specific Timeline Recommendation

Wait 3-7 days after nausea resolution before adding Wellbutrin 100mg SR once daily in the morning. If nausea persists beyond one week despite antiemetic therapy, reduce the Strattera dose before considering bupropion addition 2. This staged approach allows proper attribution of any new adverse effects and maximizes the likelihood of tolerating the combination for the 6-8 weeks needed to assess efficacy 5.