MAOIs for Migraine Treatment
Direct Answer
MAOIs are not recommended for migraine treatment in current clinical practice and are notably absent from modern migraine treatment guidelines, which prioritize NSAIDs, triptans, and CGRP antibodies instead. 1, 2
Current Guideline Recommendations
Modern migraine treatment guidelines do not include MAOIs in their treatment algorithms:
Acute Migraine Treatment
- First-line therapy: NSAIDs (aspirin, ibuprofen, naproxen) or triptans for moderate-to-severe attacks 1, 2
- Second-line therapy: Antiemetics (metoclopramide, prochlorperazine) or dihydroergotamine 1, 2
- Third-line therapy: Ditans or gepants for triptan failures 1
Preventive Migraine Treatment
- First-line: Beta-blockers (propranolol, metoprolol), topiramate, or candesartan 1
- Second-line: Flunarizine, amitriptyline, or sodium valproate (men only) 1
- Third-line: CGRP monoclonal antibodies 1
MAOIs are conspicuously absent from all tiers of both acute and preventive treatment recommendations in the most recent (2021) Nature Reviews Neurology guidelines. 1
Historical Context and Safety Concerns
Why MAOIs Are Avoided
The 2002 American Family Physician guideline explicitly warns against combining MAOIs with common migraine medications:
- Meperidine is contraindicated with MAOI use within 15 days due to risk of severe adverse reactions 1
- Isometheptene combinations are contraindicated with MAOI use within 14 days 1
These drug-drug interaction concerns make MAOIs incompatible with standard migraine treatment approaches, where patients need reliable acute medications available at all times.
Dietary Restrictions Create Practical Barriers
MAOIs require strict dietary restrictions to avoid hypertensive crises:
- Tyramine-containing foods (aged cheeses, certain meats, yeast extracts, certain alcoholic beverages) can trigger life-threatening blood pressure elevations with as little as 8-10 mg tyramine ingested 3
- Sympathomimetic medications (phenylephrine, oxymetazoline) must be avoided 3
- Serotonergic drugs (dextromethorphan, chlorpheniramine) can cause dangerous interactions 3
These restrictions are particularly problematic for migraine patients who may need over-the-counter decongestants or cough medications during concurrent illnesses. 3
Limited Historical Evidence
While older research suggested potential benefit, the evidence is weak and outdated:
- A 1995 study showed phenelzine reduced migraine frequency and severity, but this was an open trial without modern methodological standards 4
- A 1997 retrospective analysis of moclobemide (a reversible MAO-A inhibitor) showed improvement in 35 of 42 migraine patients, but the authors themselves acknowledged the need for controlled studies to verify results 5
- Neither of these studies led to incorporation of MAOIs into evidence-based guidelines, suggesting the risk-benefit ratio was unfavorable 1, 6
Clinical Bottom Line
Do not use MAOIs for migraine treatment. The combination of:
- Absence from all modern treatment guidelines 1, 2
- Dangerous interactions with standard migraine medications 1
- Burdensome dietary restrictions 3
- Availability of safer, more effective alternatives 1, 2
makes MAOIs inappropriate for migraine management in contemporary practice.
What to Do Instead
For patients with treatment-resistant migraine:
- Optimize acute treatment: Trial different triptans sequentially, as failure of one does not predict failure of others 2
- Add preventive therapy: Use first-line agents (beta-blockers, topiramate, candesartan) if headaches occur ≥2 days per month despite optimized acute treatment 1
- Escalate to CGRP antibodies: Consider erenumab, fremanezumab, galcanezumab, or eptinezumab for refractory cases 1
If a patient is already on an MAOI for depression, coordinate with psychiatry to transition to a different antidepressant class before initiating standard migraine therapies, as MAOIs are only recommended as third-, fourth-, or fifth-line depression treatments. 6