Lamotrigine for Migraine Prophylaxis
Lamotrigine is not recommended for migraine prophylaxis based on current evidence, as it has not shown efficacy for reducing migraine frequency in clinical trials. 1
Evidence Assessment
The 2023 VA/DoD Clinical Practice Guideline for the Management of Headache does not include lamotrigine among recommended medications for migraine prophylaxis 1. This is the most recent and authoritative guideline on the topic, which specifically recommends:
Strong recommendations for:
- Candesartan or telmisartan
- Erenumab, fremanezumab, or galcanezumab
Weak recommendations for:
- Topiramate
- Valproate
- Propranolol
- Lisinopril
- Oral magnesium
- Memantine
- Atogepant
- OnabotulinumtoxinA (for chronic migraine only)
Notably, the guideline specifically recommends against gabapentin for migraine prophylaxis but makes no mention of lamotrigine, suggesting insufficient evidence to warrant inclusion 1.
Research on Lamotrigine for Migraine
Clinical studies have shown:
A randomized controlled trial comparing lamotrigine with topiramate and placebo found that lamotrigine was less effective than topiramate for reducing migraine frequency and intensity 2.
A double-blind randomized placebo-controlled trial specifically investigating lamotrigine for migraine prophylaxis found it ineffective, with placebo actually showing greater improvement 3.
While lamotrigine has shown some efficacy specifically for migraine aura, it has not demonstrated effectiveness for headache prevention 4.
Special Considerations
Migraine with Aura: Lamotrigine may have a specific role in treating migraine aura rather than the headache component. It has been reported as "the treatment of choice in the prevention of migraine aura, but is not efficacious in the treatment of headache" 4.
Migraine-Related Vertigo: One observational study suggested lamotrigine may help with migraine-related vertigo symptoms, with greater effect on vertigo than on headache frequency 5.
Recommended First-Line Prophylactic Options
Based on the strongest evidence from current guidelines 1, the following medications should be considered before lamotrigine:
- Angiotensin receptor blockers: Candesartan or telmisartan (strong recommendation)
- CGRP monoclonal antibodies: Erenumab, fremanezumab, or galcanezumab (strong recommendation)
- Other options with weak recommendations:
- Topiramate (50-200 mg/day)
- Valproate (500-1500 mg/day)
- Propranolol (80-240 mg/day)
- Lisinopril
- Oral magnesium
Safety Considerations
Lamotrigine carries important safety concerns:
- High incidence of skin rashes, including potential for serious reactions like Stevens-Johnson syndrome
- Need for slow dose titration to minimize adverse effects 3
- Potential teratogenic effects in women of childbearing potential 6
Conclusion
For migraine prophylaxis, clinicians should select from medications with established efficacy as outlined in current guidelines. While lamotrigine may have a limited role in patients with frequent aura, it should not be used as a general migraine prophylactic agent due to lack of efficacy for headache prevention and potential for adverse effects.