What about using Cafergot (ergotamine and caffeine) for migraines?

Cafergot (Ergotamine/Caffeine) for Migraine Treatment

Cafergot is no longer recommended as first-line therapy for acute migraine and has been largely superseded by triptans and NSAIDs, which demonstrate superior efficacy, faster onset, and better tolerability. 1

Current Guideline Position

• Intranasal dihydroergotamine (DHE) has good evidence for efficacy and safety as monotherapy for acute migraine attacks, but oral ergotamine compounds like Cafergot are not mentioned in current first-line recommendations 1
• The American Headache Society downgraded ergotamine preparations from "effective" to "probably effective" (Level B evidence) in their 2015 guidelines, reflecting weaker evidence compared to triptans and NSAIDs 2
• Ergotamine/caffeine compounds are recommended only for moderate to severe attacks when administered early, but are positioned behind triptans in treatment algorithms 2

Comparative Efficacy Evidence

The clinical trial data consistently shows Cafergot underperforms compared to modern alternatives:

• Eletriptan 80mg achieved 68% headache response at 2 hours versus only 33% with Cafergot (p<0.001), with pain-free rates of 38% versus 10% respectively 3
• Sumatriptan 100mg produced 66% headache improvement at 2 hours compared to 48% with Cafergot (p<0.001), with significantly faster onset of relief 4
• Both triptans were significantly more effective than Cafergot at reducing associated symptoms including nausea, photophobia, and phonophobia 3, 4

Critical Safety Concerns from FDA Labeling

The FDA label highlights serious risks that limit Cafergot's utility:

• Absolute contraindication with potent CYP 3A4 inhibitors (macrolide antibiotics, protease inhibitors) due to risk of serious vasospasm 5
• Fibrotic complications including retroperitoneal fibrosis, pleuropulmonary fibrosis, and cardiac valvular thickening with long-term continuous use 5
• Cafergot should not be used for chronic daily administration due to these fibrotic risks 5
• Potential for serious toxicity even with less potent CYP 3A4 inhibitors (fluconazole, fluoxetine, grapefruit juice, metronidazole) 5

Medication Overuse Headache Risk

• Ergotamine-containing compounds can lead to medication-overuse headache and rebound headaches when used frequently, similar to butalbital compounds 6
• Acute therapy should be limited to no more than twice weekly to prevent this complication 1, 2

When Cafergot Might Still Be Considered

Despite its limitations, there are narrow circumstances where it may have a role:

• Lower recurrence rates within 48 hours compared to sumatriptan, though this advantage is offset by slower onset and lower initial efficacy 4
• Significantly lower drug acquisition cost compared to triptans, though cost-effectiveness analyses show triptans dominate when accounting for total societal costs and QALYs 7
• May be considered when triptans are contraindicated or have failed, though other options (NSAIDs, antiemetics) should be tried first 1

Practical Algorithm for Acute Migraine Treatment

Mild to moderate attacks:

• First-line: NSAIDs (ibuprofen, naproxen, aspirin) or combination acetaminophen/aspirin/caffeine 1

Moderate to severe attacks:

• First-line: Oral triptans (sumatriptan, rizatriptan, zolmitriptan) 1
• Second-line: Intranasal DHE (not oral ergotamine) 1
• Cafergot only if above options contraindicated or failed 2

Key pitfall to avoid: Do not prescribe Cafergot to patients taking macrolide antibiotics, azole antifungals, or any CYP 3A4 inhibitors due to risk of life-threatening vasospasm 5