Special information regarding the use of methysergide
In 2014 the European Medicines Agency recommended restrictions on the use of methysergide-containing medicines.
Review of methysergide use
The Agency’s Committee for Medicinal Products for Human Use (CHMP) conducted a review of the use of methysergide and made new recommendations following reports of fibrosis seen with methysergide use. Fibrosis is a condition in which fibrous (scar) tissue accumulates in the body’s organs potentially damaging them.
Methysergide medicines are now only to be used for preventing severe intractable migraine and cluster headache when standard medicines have failed. Methysergide should no longer be used to treat any other health conditions.
Treatment with methysergide will only be considered for:
- Prophylactic treatment of severe intractable migraine (with or without aura) in adults, when treatment with standard medicines has failed. Previous treatment must have included treatment with medicines of other classes for at least 4 months at the maximum tolerated dose;
- Prophylactic treatment of episodic and chronic cluster headache in adults when treatment with standard medicines has failed. Previous treatment must have included treatment with medicines of at least 2 classes for a minimum of 2 months.
Methysergide treatment should only be started and supervised by a specialist doctor with experience in treating migraine and cluster headache. Migraine and cluster headache patients should be screened for fibrosis before the start of methysergide treatment and should have additional screenings every 6 months. Treatment must be discontinued if symptoms of fibrosis occur. The symptoms of fibrosis often take some time to appear and without screening the diagnosis may come too late to prevent damage to organs.
During treatment with methysergide, a treatment-free period of at least 4 weeks must be allowed between treatment courses at least every 6 months. Headache specialists will be able to re-assess the need to continue treatment with methysergide by checking whether symptoms return after the periodic breaks in treatment.
The Committee noted that there is evidence of the effectiveness of methysergide when used for prevention in those who regularly get migraine and cluster headaches and for whom treatment options are limited.
The prescribing information for physicians and information in the patients’ information leaflet will be updated. The CHMP recommendations will now be forwarded to the European Commission, which will issue a final legally-binding decision.
The identification of a manufacturer for methysergide is being pursued however there is no definite information as yet.
Patients who have any questions should speak to their doctor or pharmacist.
If you would like more information about this please see the European Medicines Agency‘s website.
Availability of methysergide
Unfortunately the drug manufacturers of methysergide have ceased production of this medicine and the lack of availability of methysergide is now world-wide. To date, efforts to identify a new manufacturer for methysergide have proved unsuccessful.
Statement from the British Association for the Study of Headache (BASH):
Methysergide was introduced for migraine prophylaxis in 19591. It remains a very important therapy for migraine and cluster headache, particularly where first line treatment fails2. The first double blind cross over study in 60 patients showed a 50% responder rate of 58% with a placebo response of 26%3. The risk of fibrotic complications mainly retroperitoneal fibrosis has been the main side effect seen in only a minority of patients. In a series of 500 patients, two cases were reported4 and the risk was cited as 1% in a larger series of 1000 patients5. The risk is negligible with use of no more than 6 mg per day and a break of one month following 6 months of treatment6. Using this regime not a single case has been reported in the last 50 years.
The availability of other prophylactic agents has seen a reduction in the use of methysergide, although it remains a very effective treatment in those resistant to first line drugs. For some this is the only treatment that has worked in minimising the attacks in migraine and cluster headache. The short term safety is comparable to many other agents and the likely benefits in these patients outweigh the very small long term risk that requires minimal monitoring.
We feel strongly that such an effective drug that has been the lifeline for many intractable migraine and cluster headache sufferers should remain available to neurologists and headache specialists.
- Sicuteri F. Prophylactic and therapeutic properties of l-methysergic acid butanolamide in migraine: a preliminary report. Int Arch Allergy 1959; 15:300-7.
- Lance JW, Goadsby PJ. Mechanism and Management of Headache. (7th ed.) New York: Elsevier, 2005.
- Pedersen E, Moller CE. Methysergide in Migraine Prophylaxis. Clinical Pharmacology and Therapeutics 1966; 7:520-6.
- Graham JR. Methysergide for the prevention of headache; experience in five hundred patients over three years. New Eng. J. Med. 1964; 270:132-9.
- Graham JR, Suby HI, LeCompte PR, Sadowsky NL. Fibrotic disorders associated with methysergide therapy for headache. New Eng. J. Med. 1966; 274:360-8.
- Bana DS, MacNeal PS, LeCompte PM, Shah Y, Graham JR. Cardiac murmurs and endocardial fibrosis associated with methysergide therapy. Am Heart J 1974; 88:640-55.