Alternative Treatments for Acute Migraine in Patients Unable to Take Triptans
For patients unable to take triptans, NSAIDs should be used as first-line therapy for acute migraine attacks, with CGRP receptor antagonists (gepants) or 5-HT1F receptor agonists (ditans) as effective second-line options that do not have vascular contraindications. 1, 2
First-Line Options
NSAIDs
- Ibuprofen: 400-600mg per dose 1
- Naproxen sodium: 500-550mg per dose 1
- Acetaminophen: Effective for mild to moderate attacks 2
NSAIDs are recommended by the American College of Physicians as first-line therapy for acute migraine attacks, particularly in patients who cannot take triptans 1. These medications are widely available, cost-effective, and have a well-established safety profile.
Second-Line Options
CGRP Receptor Antagonists (Gepants)
- Ubrogepant (Ubrelvy):
- Dosing: 50-100mg orally 3
- Advantages: No vascular contraindications, making it suitable for patients with cardiovascular disease 2
- Limitations: Maximum 8 days per month to prevent medication overuse headache 1
- Efficacy: Significantly superior to placebo for pain freedom (19.2% vs 11.8% at 2 hours) and most bothersome symptom freedom (38.6% vs 27.8%) 3
- Adjustment needed with CYP3A4 inhibitors 3
5-HT1F Receptor Agonists (Ditans)
- Lasmiditan (Reyvow):
Rescue Medications for Severe Attacks
Antiemetics
- Should be considered even if vomiting is not present, as nausea itself can be disabling 1
- Particularly useful when significant nausea/vomiting accompanies migraine
Opioids and Butalbital-Containing Compounds
- Recommended only as rescue medications for severe attacks that don't respond to first-line or second-line treatments 1
- Should be limited due to risk of dependence and medication overuse headache 2
Non-Pharmacological Options
Evidence-Based Approaches
- Relaxation training: Effective for prevention and may help during attacks 6
- Thermal biofeedback combined with relaxation training 6
- Cognitive-behavioral therapy: May help prevent migraines 6
- Regular aerobic exercise or strength training: Helps with prevention 1
Other Options with Mixed Evidence
- Acupuncture: May be worth trying in patients who want to minimize medication use 6
- Neuromodulatory devices: Remote electrical neuromodulation has the strongest evidence 5
- Maintaining regular sleep schedule and adequate hydration 1
Treatment Algorithm for Triptan-Ineligible Patients
Start with NSAIDs:
- Try ibuprofen 600mg or naproxen sodium 550mg at first sign of migraine
- Take with food to minimize GI side effects
If NSAIDs are ineffective or contraindicated:
- Try a gepant (ubrogepant 50-100mg)
- OR lasmiditan (dose based on prescribing information)
- Choose based on patient's comorbidities and contraindications
For attacks with significant nausea:
- Add an antiemetic regardless of whether vomiting is present
For rescue therapy:
- Consider antiemetics if not already used
- Opioids or butalbital-containing compounds only if other options fail
Incorporate non-pharmacological approaches:
- Relaxation techniques during attacks
- Regular exercise, consistent sleep schedule, and trigger avoidance for prevention
Important Considerations
- Medication overuse: Limit NSAIDs to no more than 15 days per month and gepants to no more than 8 days per month to prevent medication overuse headache 1
- Early treatment: Counsel patients to treat early in the attack when pain is still mild for better efficacy
- Tracking: Encourage patients to maintain a headache diary to track frequency, severity, triggers, and response to treatment 1
The stratified-care approach (assigning treatment based on migraine severity) is superior to the step-care approach (starting with safest, least expensive options and progressing) 6, so treatment selection should consider the typical severity and disability of the patient's migraine attacks.