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Drug Quality of evidence* Scientific effect* Clinical impression of effect* Adverse effects Role (by consensus) * See Appendix 2 for explanations of quality of evidence, scientific effect, and clinical impression of effect. ? = not known; NSAIDs = nonsteroidal anti-inflammatory drugs; ASA = acetylsalicylic acid. Triptans (serotonin1B/1D receptor agonists) Sumatriptan nasal spray A +++ +++ Occasional Moderate-to-severe migraine. Useful when nonoral route needed. Less severe migraine when nonopiate medications fail. Oral triptans Moderate-to-severe migraine. Less severe migraine when nonopiate medications fail. Naratriptan A ++ ++ Infrequent Rizatriptan A +++ +++ Occasional Sumatriptan A +++ +++ Occasional Zolmitriptan A +++ +++ Occasional Sumatriptan SC A +++ +++ Frequent Moderate-to-severe migraine. Useful when nonoral route needed. Less severe migraine when nonopiate medications fail. Ergot alkaloids and derivatives DHE IV B ++ +++ Frequent Low recurrence. DHE SC/IM B +++/++ +++ Occasional Moderate-to-severe migraine. Less severe migraine when nonopiate medications fail. DHE IV plus antiemetics B +++ +++ Frequent Status migrainosus. Therapy of choice in emergency department. DHE nasal spray A ++ ++ Occasional Moderate-to-severe migraine. Less severe migraine when nonopiate medications fail. Low recurrence. Ergotamine B + ++ Frequent Consider for selected patients with moderate-to-severe migraine. Ergotamine plus caffeine Antiemetics Chlorpromazine IM/IV C/B ++ ++ Mild to moderate Adjunct therapy. May be choice for acute therapy. Metoclopramide IM B + + Infrequent to occasional Adjunct therapy. May be choice for acute therapy. PR/IV B ++ ?/++ Prochlorperazine PR/IM B +++ +/++ Occasional IM/IV adjunct first-line therapy in emergency department or office; consider PR as adjunct. IV B +++ +++ Frequent NSAIDs and nonopiate analgesics Acetaminophen B 0 + Infrequent Pregnant migraineur. Ketorolac IM B + ++ Infrequent Consider in emergency department. Oral NSAIDS Occasional First-line for mild-to-moderate migraine. Aspirin A ++ ++ Diclofenac K B ++ ++ Flurbiprofen B + ++ Ibuprofen A ++ ++ Naproxen B + ++ Naproxen sodium A ++ ++ Combination analgesics Acetaminophen, aspirin, caffeine A +++ ++ Infrequent First-line for migraine. Barbiturate hypnotics Butalbital, ASA, caffeine C ? +++ Occasional Occasional use for moderate-to-severe migraine. Limit use due to risk of overuse. Butalbital, ASA, caffeine, codeine B ++ +++ Opiate analgesics Butorphanol nasal spray A +++ +++ Frequent Moderate to severe migraine; rescue therapy. Limit use. Opiates—oral combinations A ++ ++ Occasional Moderate to severe migraine; rescue therapy. Acetaminophen, codeine combinations Limit use. Opiates—parenteral B ++ ++ Frequent Reserved for emergency department use or rescue medication. Butorphanol IM Limit use. Meperidine IM/IV Methadone IM Other medications Corticosteroids C + ++ Infrequent Rescue therapy in status migrainosus. IV plus antiemetics Dexamethasone Hydrocortisone Isometheptene compound B + ++ Infrequent Mild-to-moderate headache. Lidocaine IN B ++ ? Frequent Uncertain. Group 1* Group 2† Group 3‡ Group 4§ Group 5¶ * Proven, pronounced statistical and clinical benefit (at least two double-blind, placebo-controlled studies and clinical impression of effect). † Moderate statistical and clinical benefit (one double-blind, placebo-controlled study and clinical impression of effect). ‡ Statistically but not proven clinically or clinically but not proven statistically effective (conflicting or in consistent evidence). § Proven to be statistically or clinically ineffective (failed efficacy versus placebo). Clinical and statistical benefits uknown (insufficient evidence available). Specific Acetaminophen plus codeine PO Butalbital, aspirin, plus caffeine PO Acetaminophen PO Dexamethaxone IV Naratriptan PO Butalbital, aspirin, caffeine, plus codeine PO Ergotamine PO Chlorpromazine IM Hydrocortisone IV Rizatriptan PO Butorphanol IM Ergotamine plus caffeine PO Granisetron IV Sumatriptan SC, IN, PO Chlorpromazine IM, IV Metocloproamide IM, PR Lidocraine IV Zolmitriptan PO Diclofenac K, PO DHE SC, IM, IV, IN Ergotamine plus caffeine plus pentobarbital plus Bellafoline® PO DHE IV, plus antiemetic Flurbiprofen, PO Nonspecific Isometheptene CPD, PO Acetaminophen, aspirin, plus caffeine PO Ketorolac IM Aspirin PO Lidocaine IN Butorphanol IN Meperidine IM, IV Ibuprofen PO Methadone IM Naproxen sodium PO Metoclopramide IV Prochlorperazine IV Naproxen PO Prochlorperazine IM, PR Therapies Quality of evidence* Scientific effect* Clinical impression of effect* Adverse effects Group† * See Appendix 2 for explanations of quality of evidence, scientific effect, and clinical impression of effect. † Scale 1–5; see text for definitions. ? = not known; NSAIDs = nonsteroidal anti-inflammatory drugs. Antiepileptics Carbamazepine B ++ 0 Occasional to frequent 5 Divalproex sodium/sodium valproate A +++ +++ Occasional to frequent 1 Gabapentin B ++ ++ Occasional to frequent 2 Topiramate C ? ++ Occasional to frequent 3a Antidepressants Tricyclic antidepressants Amitriptyline A +++ +++ Frequent 1 Nortriptyline C ? +++ Frequent 3a Protriptyline C ? ++ Frequent 3a Doxepin, imipramine C ? + Frequent 3a Selective serotonin reuptake inhibitors Fluoxetine B + + Occasional 2 Fluvoxamine, paroxetine, sertraline C ? + Occasional 3a Monoamine oxidase inhibitors Phenelzine C ? +++ Frequent 3b Other antidepressants Bupropion, mirtazepine, trazodone, venlafaxine C ? + Occasional 3a Beta-blockers Atenolol B ++ ++ Infrequent to occasional 2 Metoprolol B ++ +++ Infrequent to occasional 2 Nadolol B + +++ Infrequent to occasional 2 Propranolol A ++ +++ Infrequent to occasional 1 Timolol A +++ + Infrequent to occasional 1 Calcium channel blockers Diltiazem C ? 0 Infrequent to occasional 3a Nimodipine B + ++ Infrequent to occasional 2 Verapamil B + ++ Infrequent to occasional 2 NSAIDs Aspirin B + + Infrequent 2 Fenoprofen Flurbiprofen Mefenamic acid Ibuprofen C ? + Infrequent 3a Ketoprofen B + + Infrequent 2 Naproxen/naproxen sodium B + + Infrequent 2 Serotonin antagonists Cyproheptadine C ? + Frequent 3a Methysergide A +++ +++ Frequent 4 Other Feverfew B ++ + Infrequent 2 Magnesium B + + Infrequent 2 Vitamin B2 B +++ ++ Infrequent 2 Group 1† Group 2‡ Group 3§ Group 4¶ Group 5∥ * Does not include combination products. † Medium to high efficacy, good strength of evidence, and mild-to-moderate side effects. ‡ Lower efficacy than those listed in first column, or limited strength of evidence, and mild-to-moderate side effects. § Clinically efficacious based on consensus and clinical experience, but no scientific evidence of efficacy. ¶ Medium to high efficacy, good strength of evidence, but with side effect concerns. ∥ Evidence indicating no efficacy over placebo. Amitriptyline B-blockers A: Antidepressants Methysergide Acebutolol Divalproex sodium Atenolol/metoprolol/nadolol Doxepine Carbamazepine Propranolol/timolol Fluvoxamine Clomipramine, clonazepam Ca-blockers Imipramine Clonidine Nimodipine/verapamil Mirtazepine Indomethacin Nortriptyline Nicardipine NSAIDs Paroxetine Nifedipine Aspirin/fenoprofen/flurbiprofen Protriptyline Pindolol Ketoprofen Sertraline trazodone Mefenamic acid Venlafaxine Neproxen Cyproheptadine diltiazem Naproxen sodium Ibuprofen Fluoxetine (racemic) Tiagabine Gabapentine Topiramate Other B: (side effect concerns) Feverfew Methylergonovine (methylergometrine) Magnesium vitamin B2 Phenelzine
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