Is it safe to use Strattera (atomoxetine) and Wellbutrin (bupropion) together in patients with comorbid Attention Deficit Hyperactivity Disorder (ADHD) and depression?

Safety of Combined Strattera (Atomoxetine) and Wellbutrin (Bupropion) in ADHD with Depression

Combining atomoxetine (Strattera) and bupropion (Wellbutrin) should be approached with caution in patients with comorbid ADHD and depression, as there are no controlled studies specifically evaluating this combination, though clinical experience suggests it may be used with careful monitoring. 1

Pharmacological Considerations

Mechanism of Action

• Atomoxetine: Selective norepinephrine reuptake inhibitor that works by inhibiting presynaptic norepinephrine reuptake in the prefrontal cortex 2
• Bupropion: Aminoketone antidepressant that acts as a non-competitive antagonist of nicotinic acetylcholine receptors and inhibits the reuptake of dopamine and norepinephrine 3

Potential Interaction Concerns

• Both medications affect noradrenergic pathways, potentially leading to additive effects
• No specific warnings against this combination exist in the literature, but the American Academy of Child and Adolescent Psychiatry practice parameters note that clinicians should proceed with caution when combining bupropion with other ADHD treatments 1

Clinical Approach to Management

Assessment Before Combination Therapy

• Evaluate cardiovascular status (blood pressure, heart rate, family history of sudden death or arrhythmias)
• Assess baseline liver function, especially important for atomoxetine
• Screen for seizure risk (bupropion lowers seizure threshold)
• Evaluate suicide risk (atomoxetine carries a black box warning for suicidal ideation)

Recommended Monitoring Protocol

• Regular vital sign measurements (blood pressure, heart rate)
• Monitor for emergence of:
  • Agitation or worsening anxiety
  • Sleep disturbances
  • Appetite changes and weight loss
  • Suicidal ideation (particularly important with atomoxetine) 4
• Periodic liver function tests for patients on atomoxetine

Alternative Treatment Considerations

For ADHD with Depression

1. Sequential approach: Stabilize mood first, then address ADHD symptoms 4
2. Monotherapy options:
   • Atomoxetine alone has shown efficacy for ADHD with comorbid depressive symptoms 5, 6
   • Bupropion alone has demonstrated efficacy for ADHD symptoms in adults 3

Special Populations

• Patients with bipolar disorder: Use extreme caution with this combination as both medications may potentially trigger manic episodes 7
• Patients with substance use disorders: Atomoxetine may be preferred over stimulants due to lower abuse potential 4, 2

Clinical Caveats

• Start with lower doses of each medication and titrate slowly
• Consider atomoxetine monotherapy first for ADHD with comorbid depression before adding bupropion
• If using the combination, maintain the lowest effective dose of each medication
• Be vigilant for signs of increased noradrenergic side effects (tachycardia, hypertension, excessive sweating)
• Document the clinical rationale for combination therapy in the medical record

While there is limited research specifically on this combination, the absence of explicit contraindications in guidelines suggests it may be used with appropriate caution and monitoring in patients who have not responded adequately to monotherapy.