Ergotamine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Ergotamine: From Migraine to Migraine with Brainstem Aura
One-Sentence Summary
Ergotamine is an ergot alkaloid originally used to treat migraine and cluster headache. The TxGNN model predicts it may be effective for migraine with brainstem aura, but there are currently no registered clinical trials, and the 20 publications retrieved are mostly general migraine reviews and guidelines rather than studies specific to this subtype.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Migraine disorder, cluster headache, paroxysmal hemicrania, hemicrania continua (from the knowledge graph; the Singapore licence has no indication text) |
| Predicted New Indication | Migraine with brainstem aura |
| TxGNN Prediction Score | 98.93% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on the analysis available, ergotamine is an established antimigraine agent. It acts as a 5-HT1B/1D agonist, with additional activity at alpha-adrenergic and dopamine receptors. This causes cranial vasoconstriction and inhibits the release of neuropeptides from the trigeminal nerve.
Migraine with brainstem aura is a subtype of migraine, which is already an established indication for ergotamine. The mechanistic link is therefore strong, and the model's high score is understandable.
However, there is an important caution. Vasoconstrictors are traditionally used with caution, or avoided, in brainstem aura and hemiplegic-type migraines, because of a theoretical vascular risk. No studies specific to this subtype were found, so this concern cannot be resolved with current evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The publications are mainly reviews. The most relevant ones are shown below.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25600718 | 2015 | Review | Headache | American Headache Society evidence assessment of drugs for acute migraine treatment in adults |
| 9009471 | 1997 | Review | Headache | Dosing and administration of ergotamine tartrate and dihydroergotamine; oral ergotamine suits slowly evolving migraine without early nausea or vomiting |
| 1602293 | 1992 | Double-blind crossover trial | J Intern Med | Ketoprofen vs ergotamine suppositories in acute migraine without aura (50 patients); ketoprofen was found more effective |
| 31213753 | 2018 | Double-blind trial | Hippokratia | Ergotamine-based five-component combination compared with sumatriptan in migraine without aura |
| 20187861 | 2010 | Review | Expert Rev Neurother | Management of sporadic and familial hemiplegic migraine; no clinical trials have been conducted in these forms |
| 7551126 | 1995 | Review | Curr Opin Neurol | Acute treatment of migraine attacks, including ergotamine and dihydroergotamine |
| 12917936 | 2003 | Review | Cochrane Database Syst Rev | Oral sumatriptan for acute migraine (a different drug) |
| 7816788 | 1994 | Review | Pharmacol Toxicol | Migraine diagnosis and pathophysiology |
| 38043968 | 2023 | Review | Handb Clin Neurol | History of migraine |
| 41833043 | 2026 | Review | CNS Neurol Disord Drug Targets | Pharmacology and pharmacogenomics of anti-migraine drugs |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11746P | CAFFOX TABLET | Tablet | Not stated |
Safety Considerations
Contraindications flagged by the knowledge graph (these come from network relationships, not from package insert text):
- Cardiovascular: hypertension, coronary artery disease, thrombophlebitis
- Liver and kidney: liver failure, liver disease, hepatic coma and encephalopathy, kidney disease, gallbladder disease
- Blood: thrombocytopenia, neutropenia, agranulocytosis
- Gastrointestinal: gastric ulcer, peptic ulcer disease
- Neurological and psychiatric: epilepsy, insomnia, anxiety disorder, neurotic disorder, dysthymic disorder, substance abuse/dependence
- Respiratory: chronic obstructive pulmonary disease, obstructive sleep apnoea
- Metabolic and other: porphyria, benign prostatic hyperplasia, pyoureter
Drug Interactions (100 interactions recorded; selected examples):
- Major: isometheptene, epinephrine, ephedrine, lorcaserin, clarithromycin, fenfluramine, dexfenfluramine
- Moderate: doxycycline, tetracycline, minocycline, aprepitant, dexamethasone, cimetidine, miconazole, clotrimazole
The literature also records serious ergotamine adverse effects, including myocardial infarction, limb ischaemia, gangrene, fibrotic valvular heart disease, and medication-overuse headache.
Please refer to the package insert for authoritative warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic link is strong because the predicted condition is a subtype of an existing indication. However, the evidence is only at L4, with no clinical trials and no ergotamine studies specific to this subtype. The theoretical vascular risk in brainstem aura and the broad list of flagged contraindications and major interactions add further caution.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Singapore regulator (HSA), which are currently missing
- Detailed mechanism of action data (MOA) from DrugBank
- Clinical or observational evidence on the vascular safety of ergotamine in brainstem aura and hemiplegic-type migraine
- Review of the approved indication and formulation of the single Singapore licence (a tablet whose indication text is blank)
Other predicted indications (for reference)
| Predicted Indication | Score | Evidence Level | Assessment | |------|------|------|------| | Trigeminal autonomic cephalalgia | 91.67% | L4 | Mostly overlaps with the existing cluster headache indication; literature is narrative reviews | | Headache disorder | 93.06% | L4 | Broad parent category with little new information | | Neuralgia | 87.79% | L4 | Evidence is mainly historical reports of migrainous neuralgia | | Hypnic headache | 92.87% | L5 | Speculative; safety concerns in older patients | | SUNCT syndrome | 93.00% | L5 | Attacks are too brief for ergotamine; lamotrigine is typically used | | Atrophoderma vermiculata, sciatic neuropathy, glossodynia, coccygodynia | 89.6–92.3% | L5 | No plausible mechanistic link; likely computational artefacts |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.