Drug	Dosage and route	Adverse effects	Efficacy	Comments
Verapamil	120 to 160 mg orally three times daily	Hypotension, bradycardia, atrioventricular block, dizziness, fatigue, nausea, constipation	In a double-blind RCT24 of 30 patients, 12 of 15 patients had a reduction in frequency of attacks within two weeks.	—
			In a double-blind study25 of 30 patients who received verapamil versus lithium, 50 percent of patients improved during first week of treatment.
Prednisone	50 to 80 mg orally daily tapered over 10 to 12 days	Increased appetite, insomnia, nervousness, hyperglycemia, dizziness, headache	In a double-blind study,26 17 of 19 patients experienced improvement in pain, and the treatment group had a lower frequency of headaches. In a retrospective study,27 14 of 19 patients had more than 50 percent headache relief.	In trial,26 improvement occurred within two days. Recurrences often occurred toward the end of the taper.27 Should take concurrently with another prophylactic medication.
Divalproex	600 to 2,000 mg daily	Nausea, somnolence, dizziness, insomnia, anorexia, weakness, thrombocytopenia, alopecia, weight gain	In an open-label study,28 nine of 15 patients experienced complete disappearance of pain, and two others markedly improved.	Use caution in patients with renal or hepatic insufficiency.
			In another open-label study28 of 26 patients, headache frequency decreased by 54 to 59 percent.*
			No RCTs.
Topiramate	25 mg orally daily for seven days, then increase dose by 25 mg daily every week to a maximum dosage of 200 mg daily	Paresthesias, cognitive effects, drowsiness, dizziness	In a retrospective chart review29 of patients with migraine and cluster headache, nine of 12 patients with cluster headaches exhibited moderate to substantial improvement. No RCTs.	—
Ergotamine	2 to 4 mg daily in divided doses	Vertigo, pruritus, nausea, paresthesias, weakness, cardiac valvular fibrosis, retroperitoneal or pleuropulmonary fibrosis, angina, myocardial infarction; may cause withdrawal symptoms if suddenly discontinued	No RCTs. Anecdotal evidence by experienced neurologist suggests effectiveness.13	Best for nocturnal attacks; contraindicated in peripheral vascular disease, hypertension, and cardiac disease; caution with renal or hepatic insufficiency; should not take concurrently with sumatriptan
Methylergonovine maleate	0.2 mg orally three or four times daily	Hypertension, nausea, vomiting, diarrhea, leg cramps, dyspnea, dizziness, tinnitus, nasal congestion, diaphoresis, palpitations, thrombophlebitis, hematuria, water intoxication, abdominal cramping, weight gain, paresthesias, amenorrhea; hallucinations in high doses	In a retrospective cross-sectional study,30 19 of 20 patients reported a decrease of more than 50 percent in headache frequency; 15 of 20 patients reported a reduction in headache intensity.	Caution in patients with peripheral vascular disease, cardiac disease, or renal or hepatic insufficiency; only for use in refractory cases; should never be used continually for longer than six months; contraindicated in pregnant and hypertensive patients; possibility of retroperitoneal, cardiac, and pleuropulmonary fibrosis
Melatonin	10 mg orally at bedtime	None reported	In a double-blind, placebo-controlled study31 of 20 patients, headache frequency was reduced in five of 10 patients in the treatment group. A more recent pilot study19 of nine patients did not show any difference in response between the treatment and placebo groups.	—