What treatment would be suitable for a patient with Attention Deficit Hyperactivity Disorder (ADHD) taking Vyvanse (lisdexamfetamine) who experiences severe migraines?

Managing Migraines in a Patient Taking Vyvanse for ADHD

For a patient on Vyvanse experiencing severe migraines, start with NSAIDs (naproxen 500-825 mg or ibuprofen 400-800 mg) plus an antiemetic (metoclopramide 10 mg) as first-line therapy, and escalate to triptans (sumatriptan 50-100 mg plus naproxen) for moderate-to-severe attacks, while strictly limiting all acute medications to no more than 2 days per week to prevent medication-overuse headache. 1

Critical Consideration: Stimulant-Migraine Connection

Vyvanse (lisdexamfetamine) can trigger or worsen migraines through its sympathomimetic effects. Before escalating pharmacotherapy, assess whether the migraines began or worsened after starting Vyvanse, as this may indicate a medication-induced component. 1

First-Line Acute Treatment Algorithm

For Mild-to-Moderate Migraines:

• Start with naproxen sodium 500-825 mg at migraine onset (ideally when pain is still mild), which can be repeated every 2-6 hours as needed, with a maximum of 1.5 g per day 1
• Add metoclopramide 10 mg orally 20-30 minutes before the NSAID to provide synergistic analgesia beyond just treating nausea, as it has direct antimigraine effects through central dopamine receptor antagonism 1
• Alternative NSAIDs include ibuprofen 400-800 mg or aspirin 1000 mg 1

For Moderate-to-Severe Migraines:

• Combination therapy with sumatriptan 50-100 mg PLUS naproxen sodium 500 mg is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours 1
• This combination should be taken early in the attack while pain is still mild for maximum effectiveness 1

Route Selection Based on Severity

Oral Route (First Choice):

• Sumatriptan 50 mg is the optimal starting dose, balancing efficacy with tolerability—it has similar efficacy to 100 mg but with fewer adverse events than the higher dose 2
• Oral sumatriptan provides pain relief in approximately 50-73% of patients within 2 hours 3

Subcutaneous Route (For Severe/Rapid-Onset Attacks):

• Subcutaneous sumatriptan 6 mg provides the highest efficacy with 59% achieving complete pain relief by 2 hours and onset within 15 minutes 1, 4
• This route is particularly appropriate for patients who rapidly reach peak intensity or have significant vomiting 1

Intranasal Route (For Nausea Without Vomiting):

• Intranasal sumatriptan 20 mg (NNT 3.5) offers non-oral administration without injection for patients with nausea who cannot tolerate tablets 1, 4

Critical Frequency Limitation

Absolutely restrict all acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1 This is the single most important pitfall to avoid, as frequent use creates a vicious cycle of worsening migraines.

When to Initiate Preventive Therapy

Start preventive therapy immediately if the patient requires acute treatment more than twice weekly, as this indicates inadequate migraine control and high risk for medication-overuse headache. 1, 5

First-Line Preventive Options:

• Propranolol 80-240 mg/day (beta-blocker without intrinsic sympathomimetic activity) is the most evidence-based first-line preventive 1, 5
• Topiramate 50-100 mg/day (typically 50 mg twice daily) is particularly appropriate if the patient has comorbid obesity, as it promotes weight loss 5
• Candesartan is an effective first-line agent, especially useful if the patient has comorbid hypertension 5

Important Preventive Therapy Considerations:

• Allow an adequate trial period of 2-3 months before determining efficacy, as preventive medications require time to demonstrate benefit 5
• Start with low doses and titrate slowly to minimize side effects and improve tolerability 5

If First-Line Triptans Fail

Try a different triptan before abandoning the class, as failure of one triptan does not predict failure of others. 1, 6

Alternative Triptans to Consider:

• Rizatriptan 10 mg reaches peak concentration in 60-90 minutes, making it the fastest oral triptan 1
• Eletriptan 40 mg or zolmitriptan 2.5-5 mg are reportedly more effective with fewer adverse reactions than sumatriptan 1
• Each triptan should be tried for 2-3 headache episodes before determining it ineffective 1

If All Triptans Fail:

• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy and is the first alternative when triptans are ineffective 1, 6
• CGRP antagonists (gepants) such as ubrogepant 50-100 mg or rimegepant are recommended as primary oral alternatives when triptans are contraindicated or ineffective, with no vasoconstriction making them safe for patients with cardiovascular concerns 1

Medications to Absolutely Avoid

Never use opioids (hydromorphone, meperidine) or butalbital-containing compounds for migraine treatment, as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time. 1 These should only be considered as absolute last-resort options when all other evidence-based treatments have failed or are contraindicated and the risk for abuse has been addressed. 1

Emergency/Urgent Care Treatment

For severe attacks requiring IV treatment:

• Metoclopramide 10 mg IV plus ketorolac 30 mg IV is the recommended first-line combination therapy, providing rapid pain relief while minimizing side effects and rebound headache risk 1
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy 1

Special Considerations for Stimulant Users

Monitor for potential interactions between acute migraine treatments and Vyvanse:

• Triptans and stimulants both have sympathomimetic effects—while not absolutely contraindicated, monitor for excessive cardiovascular stimulation 1
• Consider whether migraine frequency correlates with Vyvanse dosing schedule, as this may indicate the stimulant is a trigger requiring dose adjustment or timing modification