What is the recommended dosage and monitoring protocol for combining Wellbutrin (bupropion) and Adderall (amphetamine and dextroamphetamine) in patients with Attention Deficit Hyperactivity Disorder (ADHD)?

Combining Wellbutrin and Adderall for ADHD

The American Academy of Child and Adolescent Psychiatry explicitly states there are no studies of combining bupropion and stimulants in ADHD treatment, and clinicians should proceed with caution until further studies are available. 1

Current Evidence Status

The combination of bupropion (Wellbutrin) and amphetamine/dextroamphetamine (Adderall) lacks formal safety and efficacy data:

• No controlled trials exist examining this specific combination for ADHD treatment, making evidence-based dosing recommendations impossible 1
• The PDR does not warn against interactions between bupropion and stimulants, and no case reports of serious adverse effects from combining these agents have been documented 1
• Despite the absence of formal studies, the combination is used in clinical practice, particularly when dose-limiting side effects prevent adequate monotherapy or when comorbid conditions exist 2

If Proceeding with Combination Therapy

Pre-Treatment Requirements

Before combining these medications, complete the following assessments:

• Cardiovascular screening including baseline blood pressure, pulse, and assessment for symptomatic cardiovascular disease, as stimulants are contraindicated in symptomatic heart disease 3
• Seizure risk evaluation is critical, as bupropion lowers seizure threshold; avoid in patients with eating disorders, seizure history, or abrupt alcohol/benzodiazepine withdrawal 3
• Substance use screening, as active substance use disorders represent a relative contraindication requiring close supervision 3

Dosing Strategy

Given the lack of formal guidance, a conservative approach is warranted:

For Adderall:

• Start at 10 mg once daily in the morning 4
• Titrate by 5 mg weekly increments based on response and tolerability 4
• Maximum recommended dose is 50 mg daily for adults 4

For Bupropion XL:

• Start at 150 mg once daily in the morning 3
• Titrate to maintenance dose of 150-300 mg daily based on response 3
• Maximum dose is 450 mg per day 3

Critical sequencing consideration: Establish stable dosing on one medication before adding the second to clearly attribute any adverse effects 1

Monitoring Protocol

Enhanced monitoring is essential given the lack of safety data:

• Monthly visits until symptoms stabilize, assessing both therapeutic response and adverse effects at each adjustment using standardized ADHD rating scales 3
• Cardiovascular monitoring at each visit: Both bupropion and amphetamines cause statistically significant increases in blood pressure (bupropion +5.9 mmHg systolic, amphetamine +5.4 mmHg systolic) and heart rate (bupropion +6.9 bpm, amphetamine +7.3 bpm) 5
• Seizure vigilance: The combination may theoretically increase seizure risk through additive CNS stimulation, though no cases have been reported 1, 3

Alternative Evidence-Based Approaches

Before resorting to this unstudied combination, consider these validated strategies:

Sequential Monotherapy

• Switch stimulants first: Approximately 70% of patients respond to either dextroamphetamine or methylphenidate alone, and nearly 90% respond if both are tried 6
• Try bupropion monotherapy: Bupropion alone is more effective than placebo for adult ADHD (significant difference in CAARS scores at 6 weeks) and can be an alternative when stimulants are contraindicated 7, 8

Studied Combinations

• Clonidine plus stimulants: This combination has been studied for reducing aggression, controlling ADHD symptoms after stimulant wear-off, and counteracting insomnia; start with 0.05 mg at bedtime, never exceeding 0.3 mg/day 1, 3
• Atomoxetine augmentation: Non-stimulant alternative with no abuse potential, initiated at 40 mg/day and titrated to maximum 100 mg/day 3

Clinical Pitfalls to Avoid

• Do not assume safety based on absence of reported interactions: The lack of case reports does not equal proven safety; it reflects insufficient study 1
• Avoid starting both medications simultaneously: This prevents attribution of adverse effects to the correct agent 1
• Do not overlook additive cardiovascular effects: Both medications independently increase blood pressure and heart rate; combined effects may be additive 5
• Never use in patients with seizure risk factors: The combination theoretically compounds seizure risk through dual CNS stimulation 3

When Combination May Be Justified

The main indication for combined medication in clinical practice is dose-limiting adverse effects that prevent adequate monotherapy 2:

• Stimulant side effects (appetite suppression, insomnia) prevent dose optimization
• Comorbid depression or smoking cessation needs warrant bupropion
• Partial response to stimulant monotherapy at maximum tolerated dose

Treatment adherence improves with combined medication compared to monotherapy in observational data, particularly in females 2