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Certain medications are useful as transitional agents. These medications are used after cluster episodes to stabilize the patient until preventive maintenance becomes effective.

Methysergide. Methysergide (Sansert) is also used for preventing episodic cluster headaches. (It is not very effective for chronic cluster headaches.) Improvement usually occurs within a few days, although it may be delayed for up to two weeks. Prolonged methysergide therapy can cause serious side effects, including scarring of internal organs, so it cannot be used long term. This is not usually a problem for cluster headache patients, since they only require the drug for about four to six weeks. Nevertheless, patients should report any of the following symptoms immediately: cold, numb, and painful hands and feet; leg cramps on walking; or any type of back or chest pain.

Ergotamine. Drugs containing ergotamine (sometimes called ergots) causes contractions of smooth muscles, including those in blood vessels, and are commonly used for migraine. Taking them before an expected cluster attack produces good results for many patients. One ergot-derived drug called dihydroergotamine (DHE) is administered by injection, which can be performed by the patient at home. It is also available as a nasal spray (Migranal), which may have fewer side effects than the injection. Ergotamine itself is available in oral tablets (Ergomar, Wigraine, Ercaf) and in rectal suppositories (Cafergot). Cafergot, Wigraine, and Ercaf contain caffeine. An ergotamine inhaler is being investigated.

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Side effects of ergotamine include nausea, dizziness, tingling sensations, muscle cramps, and chest or abdominal pain. Ergotamine has toxic effects at high levels. It also causes persistent blood vessel contractions, which may pose a danger for people with heart disease or risk factors for heart attack or stroke. Pregnant women, people over 60, and those with serious, chronic health problems, particularly those of the heart and circulation, should avoid these medications altogether. As with other migraine drugs, if ergotamine is taken more than twice a week, the patient is at risk for rebound headaches when the drug is withdrawn, although cluster patients appear to be at lower risk for this effect than other headache patients.

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