What can be done to alleviate afternoon headaches in a patient taking 100 mg SR Wellbutrin (bupropion) and Adderall (amphetamine and dextroamphetamine) IR 10 mg and XR 15 mg for Attention Deficit Hyperactivity Disorder (ADHD)?

Management of Afternoon Headaches in Patient on Wellbutrin and Adderall

The most likely cause of afternoon headaches is the combined stimulant effect of Wellbutrin and Adderall, particularly with the 2 PM Adderall XR dose, and the first step is to ensure adequate hydration and consider splitting the Wellbutrin dose or switching to a different formulation.

Immediate Assessment and Likely Etiology

• Headaches occurring 12 days into Wellbutrin therapy are most commonly related to the medication's stimulant properties, which are additive with Adderall's effects 1, 2
• The timing of afternoon headaches correlates with the 2 PM Adderall XR 15 mg dose, suggesting cumulative stimulant burden as the primary mechanism 3, 4
• Bupropion (Wellbutrin) has proven efficacy for ADHD treatment but carries headache as a common side effect, particularly when combined with other stimulants 5

Stepwise Management Algorithm

First-Line Interventions (Try These First)

• Ensure adequate hydration throughout the day - stimulant medications increase metabolic rate and can lead to relative dehydration, a common headache trigger 2
• Consider splitting the Wellbutrin SR 100 mg dose to 50 mg twice daily (morning and early afternoon) to reduce peak serum levels that may be contributing to headaches 5
• Evaluate the timing of the afternoon Adderall XR dose - moving it earlier (noon instead of 2 PM) may reduce the temporal overlap of peak stimulant effects 3

Second-Line Medication Adjustments

• If headaches persist after 2-3 weeks, consider switching from Wellbutrin SR to Wellbutrin XL formulation, which provides more stable blood levels and may reduce side effects 5
• Alternatively, reduce the Wellbutrin dose temporarily to 75 mg daily while maintaining ADHD coverage with the existing Adderall regimen, then slowly titrate back up if tolerated 5
• As a last resort, discontinue Wellbutrin entirely if headaches are intolerable, as Adderall alone provides adequate ADHD coverage for most patients 3, 5

Acute Headache Treatment Options

• For mild to moderate afternoon headaches, use NSAIDs as first-line therapy: ibuprofen 400-600 mg or naproxen sodium 500 mg at headache onset 1, 6, 2
• Add caffeine (100-200 mg) with the NSAID for synergistic analgesic effect, though monitor total daily caffeine intake as it may worsen stimulant-related side effects 1
• Limit acute headache medication use to no more than 2 days per week to prevent medication-overuse headache 1, 6

Critical Pitfalls to Avoid

• Do not allow the patient to increase Adderall doses in response to perceived decreased effectiveness, as this will worsen the headache pattern 4
• Avoid using opioids or butalbital-containing compounds for these headaches, as they carry high risk for medication-overuse headache and dependency 7, 1
• Do not abruptly discontinue Wellbutrin without tapering, as this can cause withdrawal symptoms and mood destabilization 5

When to Consider Preventive Therapy

• If headaches occur more than 2 days per week despite the above interventions, initiate migraine preventive therapy rather than relying solely on acute treatments 1, 8
• First-line preventive options include propranolol 80-240 mg/day or amitriptyline 30-150 mg/day, though note that propranolol may worsen ADHD symptoms in some patients 1, 6, 8

Timeline for Reassessment

• Allow 2-3 weeks after any medication adjustment before concluding whether the intervention was effective 5
• If headaches persist beyond 4 weeks of Wellbutrin therapy despite interventions, strongly consider discontinuing it, as this suggests the medication is not well-tolerated in this patient 5