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Drug Therapy for Migraine Headache
• Initially consider step-care starting with an appropriate trial of simple analgesics (e.g.,
aspirin, acetaminophen, OTC nonsteroidal anti-inflammatory drugs (NSAIDs),Excedrin1).
• If unsuccessful, use stronger analgesics such as prescription-strength NSAIDs or
• In patients with severe, incapacitating headaches with vomiting and prostration that are
refractory to simple or combination analgesics, consider starting with the selectiveserotonin receptor agonists (SSRAs) or stronger analgesics2, such as analgesic-sedativecombinations (e.g., butalbital) with or without codeine, or prescription NSAIDs plusmetoclopramide.
• Limit opioids to patients with severe, but infrequent headaches, or the occasional
headache that is unresponsive to either DHE or SSRAs. In patients with nocturnalheadaches, the impact of side effects are not as problematic.
• Opioids also may be an alternative in patients with menstrual migraine that does
not respond to standard abortive agents.
• Consider metoclopramide when specific migraine therapy does not relieve nausea
and vomiting. As a gastric stimulant, it can help counter delayed gastric emptyingcaused by migraines.
Selective Serotonin Receptor Agonists
• Imitrex injection provides the fastest onset of action (82% efficacy at 20 minutes) and
may be most appropriate for severe migraines.
• Onset of pain relief with Imitrex nasal can occur as early as 15 minutes, but efficacy at
two hours is less than the injection at 20 minutes (62% vs. 82%).3 Efficacy at twohours is comparable to that at four hours for oral preparations.
• Maxalt and Zomig may have an earlier onset of action than oral Imitrex or Amerge.4,5
• Headache recurrence at 24 hours appears comparable for all SSRAs. The longer half-
life of Amerge may contribute to a longer duration between recurrences.
• Though Maxalt-MLT does not work faster, patients with nausea may prefer that it
dissolves on the tongue without the need to take with water.
1 Lipton RB, Stewart WF, Ryan RE, et al. Efficacy and safety of acetaminophen, aspirin and caffeine in alleviating
migraine headache pain. Arch Neurol
2 Ziegler DK. Opioids in headache treatment. Is there a role? Neurol Clin
3 Moskowitz MA, Cutrer FM. Attacking migraine headache from beginning to end. Neurology
4 Gaist D, Hallas J, Sindrup SH, Gram LF. Is overuse of sumatriptan a problem: A population based study. Eur J Clin
5 Catarci T, Fiacco F, Argentino C, et al. Ergotamine-induced headache can be sustained by sumatriptan daily intake.
• If unable to obtain relief with one SSRA, consider an alternative SSRA before resorting
Why Not Migranal?
• Intranasal DHE (Migranal) may provide a longer duration of action with lower
recurrence rates than SSRAs, but its speed of onset is slower.
• Due to their vasoconstrictive effects, Migranal should not be used within 24 hours of
serotonin agonists. Migranal should also not be used in pregnant women.
The Average Wholesale Price for acute therapy with the SSRAs or Migranal ranges from
~$14 (Zomig 2.5 mg tablet) to ~$19 (Imitrex nasal). Actual prices vary depending on
discounts and rebates.
Daily Prophylactic (chronic) Therapy6
• >2 headaches per month causing disability lasting 3 or more days, or
• Infrequent, but severely incapacitating headaches, particularly when poorly
• Abortive medication is required more than twice a week, or
• Hemiplegic migraine or infrequent headaches that are profoundly incapacitating or
that risk permanent neurologic injury.
• Prophylactic therapy may often be successfully tapered and discontinued in patients
• Consider prophylactic therapy a success if it reduces attacks by 50%. It may take 4
weeks before the initial effect and continues to increase for three months.
Efficacy of Prophylactic Drugs
There is no evidence that prophylaxis using more than one drug is superior tomonotherapy.7
6 Silberstein SD. Migraine: Diagnosis and Treatment. In
: Silberstein SD, Lipton RB, Goadsby PJ, eds. Headache in
Clinical Practice. Oxford, UK: Isis Medical Media; 1998.
7 Tfelt-Hansen P. Prophylactic pharmacotherapy of migraine. Neurol Clin
± SSRIs = Selective serotonin reuptake inhibitors
¤ Significant adverse effects
§ MAOIs = Monoamine oxidase inhibitors Beta-adrenergic Blocking Agents
• Propranolol produces an approximate 44% reduction in the frequency of attacks.8
• The cardioselective agents (e.g., atenolol, metoprolol) may be used in patients with
asthma and other respiratory disorders.
• Amitriptyline, in particular, has been shown to decrease the frequency, severity and
duration of migraine attacks. Patients suffering from both insomnia and migraine mightbenefit the sedative effects.
• Divalproex may be particularly appropriate for patients with co-existing epilepsy or
• Fatal hepatotoxicity is a serious side effect, but is rare in adults on monotherapy. Calcium Channel Blockers
• Verapamil appears to be the most effective calcium channel blocker.
• Typically have a slow onset of action, ranging from 2-8 weeks.
• Consider for patients with comorbid hypertension or a contraindication to beta-
• Patients often report an initial increase in headaches that may effect compliance.
Development of Chronic Daily Headaches
Consider analgesic rebound headache if the patient reports:
• Analgesic (including OTC), SSRA or ergotamine use more than three times a week, and
especially if daily use is reported.10,11
• Headache duration exceeding 10 hours.
• The headaches are refractory; daily or nearly daily (>20 headache days/month)
particularly with a low pain threshold.
• Headaches accompanied by asthenia, and nausea, and other gastrointestinal symptoms.
• Frequent early morning headaches.
• Increase in severity and frequency of headache attacks.
Medication withdrawal tends to result in spontaneous improvement. Prophylactic therapydoes not seem effective.
8 Holroyd KA, Penzien DB, Cordingley GE. Propranolol in the management of recurrent migraine: A meta-analytic
9 Silberstein SD, Wilmore LJ. Divalproex sodium: Migraine treatment and monitoring. Headache
Silberstein SD, Saper JR. Migraine: Diagnosis and Treatment. In
: Dalessio DJ, Silberstein SD, eds. Wolff's
Headache and Other Head Pain. New York, NY: Oxford University Press; 1993.
Mathew NT. Transformed migraine, analgesic rebound, and other chronic daily headaches. Neurol Clin
Consider drug misuse for patients with the following characteristics:
• A new patient with in-depth knowledge of a particular medication and its strengths and
• Evasive when asked about headache history, last episode, severity and frequency of
• Has specific medication requests and may be evasive about why regular physician was
not contacted for advice or prescription renewal.
• Distinguish from transformed migraine where the patient typically describes an initial
onset of migraines in their teens or 20s, eventually becoming more frequent.
Eventually, the patient develops intercurrent paroxysmal tension-type headaches thatmerge with the migraines into chronic daily headache.
Suggested Internet Site
Much of the above information came from “Managing Migraine Today (II):
Pharmacologic and Nonpharmacologic Treatment” on the JAMA Migraine Information
Center Internet site (http://www.ama-assn.org/special/migraine/migraine.htm).
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to visit this site for more information.
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