Is it safe to combine 60mg Strattera (atomoxetine) with 100mg Wellbutrin (bupropion) for a patient with Attention Deficit Hyperactivity Disorder (ADHD) or should the patient titrate down on Strattera?

Combining 60mg Strattera with 100mg Wellbutrin: Safety and Dosing Recommendations

The combination of 60mg atomoxetine (Strattera) with 100mg bupropion SR (Wellbutrin) can be used safely together with careful monitoring, but starting atomoxetine at a lower dose (40mg or less) when bupropion is already on board is the preferred approach. 1, 2

Pharmacological Interaction Profile

The primary concern with this combination involves bupropion's inhibition of CYP2D6, which is the major metabolic pathway for atomoxetine. 3 This interaction can increase atomoxetine plasma concentrations to levels similar to those seen in poor CYP2D6 metabolizers, potentially increasing exposure by 2-3 fold. 3

However, medical guidelines explicitly state that Strattera and Wellbutrin can be safely taken together with appropriate monitoring. 2 The combination follows sound pharmacological principles by targeting different neurotransmitter pathways (norepinephrine reuptake inhibition via atomoxetine and dopamine/norepinephrine effects via bupropion), which can provide additive therapeutic benefits for ADHD symptoms, particularly motivation and energy. 2, 4

Recommended Dosing Strategy

If the patient is already taking 60mg Strattera, adding 100mg Wellbutrin SR can proceed, but close monitoring in the first 24-48 hours is essential. 1 The alternative and more conservative approach would be:

• Reduce atomoxetine to 40mg daily when initiating bupropion 1
• Monitor for 7-14 days at this combination
• If well-tolerated and additional benefit is needed, consider gradual re-escalation of atomoxetine back toward 60mg 1

The standard atomoxetine dosing starts at 40mg daily with titration every 7-14 days to 60-80mg/day, with maximum dosing at the lesser of 1.4 mg/kg/day or 100mg/day. 1, 2 For bupropion SR, the typical dose is 100-150mg twice daily, with your patient's 100mg SR representing a conservative starting dose. 1, 2

Critical Monitoring Parameters

Watch specifically for these adverse effects in the first 24-48 hours after combining or adjusting doses: 1

• Autonomic symptoms: Hypertension, tachycardia, increased heart rate and blood pressure (both medications affect cardiovascular parameters) 1, 2
• Neuromuscular effects: Tremor, hyperreflexia, muscle rigidity 1
• Mental status changes: Agitation, restlessness, confusion 1
• Sleep disturbances: Insomnia (common with both medications) 2

While the monitoring parameters listed above include signs of serotonin syndrome, this is primarily a theoretical concern since neither medication has significant serotonergic activity. The more relevant concern is additive noradrenergic effects causing autonomic hyperactivity. 1

Safety Evidence

There are no published case reports of serious adverse events when combining bupropion with atomoxetine. 5 The 2002 American Academy of Child and Adolescent Psychiatry practice parameter explicitly noted: "There are no studies of the combination of bupropion and stimulants in the treatment of ADHD or other psychiatric conditions...we could locate no case reports of side effects when these agents were combined." 5 While this referred to stimulants, the principle extends to atomoxetine given its similar noradrenergic mechanism.

Both medications have been studied extensively as monotherapy for ADHD. Atomoxetine demonstrates efficacy comparable to immediate-release methylphenidate, though less than extended-release formulations. 3 Bupropion shows moderate benefit for ADHD symptoms with a favorable side-effect profile. 4, 6, 7

Contraindications and Cautions

Bupropion is absolutely contraindicated in patients with: 2

• Seizure disorders (dose-related seizure risk)
• History of stroke or brain metastases
• Current MAO inhibitor use

Both medications require monitoring for: 2

• Neuropsychiatric effects including mood changes (though recent evidence suggests lower risk than previously thought)
• Cardiovascular effects, particularly in patients with pre-existing cardiac conditions
• Hepatic function (atomoxetine exposure increases significantly in hepatic insufficiency) 3

Practical Clinical Algorithm

1. If patient is stable on 60mg atomoxetine: Add bupropion 100mg SR with intensive monitoring for 48 hours, then weekly for 4 weeks 1, 2

2. If concerned about interaction: Reduce atomoxetine to 40mg, add bupropion 100mg SR, monitor for 7-14 days, then consider re-escalating atomoxetine if needed and well-tolerated 1

3. Monitor blood pressure and heart rate at each visit during the first month of combination therapy 2

4. Schedule follow-up at 2 weeks, then monthly once stabilized 5

The 60mg/100mg combination represents conservative dosing for both medications, which provides an additional safety margin. The maximum doses are 100mg for atomoxetine (or 1.4 mg/kg/day) and 450mg for bupropion, so there is room for adjustment if needed. 1, 2