Is it safe to use Wellbutrin (bupropion) and Strattera (atomoxetine) together in individuals with Ehlers-Danlos syndrome?

Safety of Wellbutrin (Bupropion) and Strattera (Atomoxetine) Combination in Ehlers-Danlos Syndrome

There is no specific contraindication to using bupropion and atomoxetine together in patients with Ehlers-Danlos syndrome, but this combination requires careful cardiovascular monitoring given the lack of safety data and the cardiovascular risks inherent to both EDS and these medications.

Key Cardiovascular Considerations in EDS

The primary concern with any medication regimen in Ehlers-Danlos syndrome relates to cardiovascular complications, particularly in vascular EDS (type IV):

• Vascular EDS causes severe arterial fragility with risk of spontaneous arterial rupture, dissection, and aneurysm formation, with median survival of only 48 years and most deaths from arterial complications 1
• Hypermobile EDS (hEDS) is associated with postural orthostatic tachycardia syndrome (POTS) and autonomic dysfunction, requiring careful management of heart rate and blood pressure 1
• Patients with EDS frequently require treatment with heart rate-lowering agents (propranolol, ivabradine) and blood pressure management for POTS symptoms 1

Medication-Specific Risks

Atomoxetine Cardiovascular Profile

• Atomoxetine requires careful cardiovascular assessment before initiation, particularly in patients with preexisting cardiovascular disease or cardiac abnormalities 2
• Approximately 7% of patients are poor CYP2D6 metabolizers, resulting in significantly higher plasma levels and increased adverse effects 2
• Concomitant use with medications affecting CYP2D6 metabolism (including some SSRIs) can elevate atomoxetine levels, requiring dose adjustments 2

Bupropion Cardiovascular Profile

• Bupropion can increase blood pressure and heart rate, which may be problematic in patients with POTS or vascular fragility 3
• Maximum daily dose should not exceed 450 mg regardless of formulation 3

Combination Therapy Concerns

There are no published studies examining the safety or efficacy of combining bupropion with atomoxetine, so clinicians must proceed with extreme caution 3. This lack of data is particularly concerning in EDS patients who have:

• Baseline cardiovascular instability from POTS 1
• Risk of arterial complications from vascular fragility 1
• Frequent comorbid psychiatric conditions including depression, anxiety, and personality disorders requiring pharmacotherapy 4, 5

Practical Management Algorithm

If you choose to use this combination in an EDS patient:

1. Confirm EDS subtype - Vascular EDS (type IV) carries highest cardiovascular risk and may warrant avoiding this combination entirely 1, 6

2. Baseline cardiovascular assessment including:

   • Blood pressure monitoring (sitting and standing for POTS evaluation) 1
   • Heart rate assessment 1
   • ECG if any cardiac history 2
   • Consider echocardiography if vascular EDS suspected 1

3. Start with monotherapy first - Use atomoxetine alone initially (starting at 40 mg daily, titrating every 7-14 days to 60-80 mg daily, maximum 1.4 mg/kg/day or 100 mg/day) 2

4. If adding bupropion, use lowest effective doses:

   • Start bupropion SR 100 mg daily or XL 150 mg daily 3
   • Monitor blood pressure and heart rate weekly during titration 1, 2
   • Watch for additive cardiovascular effects

5. Close monitoring for suicidal ideation is mandatory with atomoxetine, especially during first months of treatment or dose changes 2

6. Consider alternative approaches:

   • Stimulants remain first-line for ADHD and may be safer with more predictable cardiovascular effects 3
   • Bupropion is less efficacious than stimulants for ADHD 3
   • If treating comorbid depression, bupropion may be particularly useful 3

Critical Safety Pitfalls

• Never assume normal cardiovascular function in EDS patients - even hypermobile EDS without obvious vascular features can have POTS 1
• Avoid arteriography in vascular EDS due to risk of arterial injury; use CT, MRI, or ultrasound for vascular imaging 6
• Be aware that psychiatric symptoms in EDS may be secondary to chronic pain and physical limitations rather than primary psychiatric disease 4, 5
• The combination lacks safety data even in healthy populations, making use in EDS particularly high-risk 3