What are the effects of Ergotamine (ergot alkaloid) use?

From the Guidelines

Ergotamine should only be considered for the treatment of moderate to severe acute episodic migraine headache in nonpregnant outpatient adults who do not tolerate or have inadequate response to combination therapy of a triptan and an NSAID or acetaminophen, as recommended by the American College of Physicians 1. When using ergotamine, it is essential to be aware of its potential side effects and contraindications, such as cardiovascular disease, hypertension, kidney or liver disease, and pregnancy.

• The typical formulation is ergotamine tartrate, often combined with caffeine (as in Cafergot), with dosing usually starting at 1-2 mg at migraine onset, followed by 1-2 mg every 30 minutes if needed, not exceeding 6 mg per attack or 10 mg per week.
• Ergotamine works by constricting blood vessels in the brain and inhibiting inflammatory neuropeptide release, effectively stopping migraine progression when taken early.
• However, due to its potential risks and the availability of safer alternatives like triptans, ergotamine is now considered a second-line treatment for migraines that don't respond to other medications, as supported by studies comparing its efficacy and safety to other treatments 1. Some key points to consider when prescribing ergotamine include:
• Counseling patients to begin treatment of migraine headache as soon as possible after its onset, using combination therapy to improve efficacy 1.
• Being aware of medication overuse headache, which is a potential complication of migraine treatment, and advising patients accordingly 1.
• Highlighting the importance of lifestyle modifications, including staying well hydrated, maintaining regular meals, securing sufficient and consistent sleep, engaging in regular physical activity, managing stress, and avoiding triggers 1.

From the FDA Drug Label

Although signs and symptoms of ergotism rarely develop even after long term intermittent use of the drug, care should be exercised to remain within the limits of recommended dosage. Ergotism is manifested by intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia Ergotamine induces vasoconstriction by a direct action on vascular smooth muscle. In chronic intoxication with ergot derivatives, headache, intermittent claudication, muscle pains, numbness, coldness and pallor of the digits may occur. If the condition is allowed to progress untreated, gangrene can result While most cases of ergotism associated with ergotamine treatment result from frank overdosage, some cases have involved apparent hypersensitivity. There are few reports of ergotism among patients taking doses within the recommended limits or for brief periods of time In rare instances, patients, particularly those who have used the medication indiscriminately over long periods of time, may display withdrawal symptoms consisting of rebound headache upon discontinuation of the drug

Ergotamine Use Precautions:

• Dosing Limits: Patients should not exceed the recommended dosage to avoid ergotism.
• Contraindications: Ergotamine should not be administered with other vasoconstrictors, CYP 3A4 inhibitors, or sympathomimetics.
• Adverse Effects: Patients should be advised to report numbness, tingling, muscle pain, weakness, or chest pain to their physician immediately.
• Pregnancy: Ergotamine is classified as Pregnancy Category X and should not be used during pregnancy due to potential teratogenic effects 2.
• Interactions: Ergotamine may interact with macrolide antibiotics, protease inhibitors, and nicotine, leading to increased risk of vasospastic reactions 3, 2, 2.

From the Research

Ergotamine Use in Migraine Treatment

• Ergotamine has been used for many years in the treatment of migraine, although its efficacy is debatable and there is a poor risk:benefit ratio due to its side effects 4.
• The drug has been associated with several side effects, including myocardial infarction, ischaemia of limb extremities, and fibrotic changes, as well as ergotamine-induced headache and subclinical ergotism with long-term use 4, 5.
• An expert group from Europe has suggested that ergotamine is the drug of choice for a limited number of migraine sufferers who have infrequent or long duration headaches and are likely to comply with dosing restrictions, but triptans are generally a better option for most migraine sufferers 6.
• The advent of triptans has revolutionized acute migraine treatment, and they have much greater specificity for the 5-HT1B and 5-HT1D receptors than ergot alkaloids, resulting in fewer side effects and greater clinical utility 7.
• Clinical practice guidelines have been formulated to describe and define the limits of ergot use, provide information on dosing, and guide physicians to avoid overuse of ergotamine tartrate (ET) by patients, as overuse can lead to physical and psychological dependence and rebound headaches 8.

Safety and Efficacy

• Ergotamine is an effective and valuable substance in the treatment of acute attacks of migraine, but it remains a potentially dangerous substance with multiple and serious side effects 5.
• The safety and efficacy of ergotamine have been evaluated in several studies, and it has been found to be safe and effective for the treatment of migraine as long as recommended dosages are not exceeded and high-risk patients are avoided 8.
• Dihydroergotamine (DHE) has also been found to be safe and effective, and it does not have the same risk of overuse and dependence as ET 8.

Clinical Use

• Ergotamine is no longer a first-line treatment for migraine due to the availability of triptans, which have a better efficacy and side-effect profile 7.
• However, ergotamine may still be used in certain cases, such as in patients who have infrequent or long duration headaches and are likely to comply with dosing restrictions 6.
• Physicians should follow clinical practice guidelines to ensure the safe and effective use of ergotamine and DHE in the treatment of migraine 8.