What are the potential interactions between Adderall (amphetamine and dextroamphetamine) and bupropion?

Potential Interactions Between Adderall and Bupropion

Caution is advised when combining Adderall (amphetamine and dextroamphetamine) with bupropion due to potential pharmacokinetic interactions that may increase the risk of adverse effects, including seizures, elevated blood pressure, and neuropsychiatric symptoms. 1

Pharmacological Mechanism of Interaction

• Both medications affect similar neurotransmitter systems, primarily dopamine and norepinephrine, which can lead to additive stimulant effects when used together 1
• Bupropion and its metabolites inhibit cytochrome P450 2D6 (CYP2D6), which may interfere with the metabolism of amphetamines, potentially increasing their plasma concentrations and effects 2

Potential Adverse Effects

Neuropsychiatric Effects

• Increased risk of neuropsychiatric symptoms including:
  • Anxiety, agitation, and insomnia 1
  • Potential for delirium, particularly in elderly patients or those with other risk factors 2
  • Possible increased risk of seizures, especially in patients with predisposing factors 1

Cardiovascular Effects

• Potential for additive effects on blood pressure and heart rate 1
• Both medications independently can cause cardiovascular stimulation, and the combination may enhance these effects 1

Laboratory Testing Considerations

• Bupropion can cause false positive results for amphetamines on urine drug screens using certain immunoassays (particularly Syva EMIT II) 3
• This could lead to misinterpretation of drug testing results in clinical or occupational settings 3

Clinical Management Recommendations

Before Initiating Combination Therapy

• Assess for contraindications to either medication:
  • History of seizures or seizure disorders 1
  • Eating disorders 1
  • Uncontrolled hypertension 1
  • Closed-angle glaucoma 1

During Combined Treatment

• Monitor vital signs regularly, particularly blood pressure and heart rate 1
• Start with lower doses of both medications when used concomitantly 1
• Consider intermittent use of stimulants rather than continuous daily dosing when possible 1
• Monitor for signs of increased stimulant effects or toxicity, including:
  • Insomnia or sleep disturbances 1
  • Excessive anxiety or agitation 1
  • Appetite suppression and weight loss 1

Special Populations

Pregnancy Considerations

• Both medications cross the placenta and should be used with caution during pregnancy 1
• If treatment is necessary during pregnancy, the lowest effective doses should be used 1
• Consider risks of untreated ADHD versus medication exposure 1

Breastfeeding Considerations

• Both medications can be present in breast milk 1
• Limited data on bupropion in breastfeeding (21 cases) shows generally no adverse events, though there have been two case reports of seizures in breastfed infants 1
• Monitor breastfed infants for irritability, poor feeding, and sleep disturbances when mothers are taking these medications 1

Research Evidence on Combination Use

• There are no formal studies specifically examining the combination of bupropion and stimulants in the treatment of ADHD or other psychiatric conditions 1
• Some research suggests that acute doses of both amphetamine and bupropion can increase cigarette smoking behavior, which may be relevant for patients using this combination who also smoke 4
• Despite bupropion's structural similarity to amphetamines, studies in individuals with histories of substance abuse show that bupropion lacks significant amphetamine-like subjective effects 5, 6

Human Pharmacology Laboratories research indicates that bupropion does not produce the same euphoric or reinforcing effects as amphetamines, suggesting a lower abuse potential despite the pharmacological overlap 5, 6