By Michael J. Marmura, MD and Stephen Silberstein, MD
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By Michael J. Marmura, MD and Stephen Silberstein, MD igraine is a common chronic and often disabling OTCs without substantial relief.2 Providers treating migraine neurological disorder characterized by attacks of must be familiar with different acute treatments, be comfortable moderate to severe headache. Migraineurs usually with individualizing treatment, and be able to combine treat- experience nausea and light and sound sensitivity ment modalities. Mduring their attacks, and many have aura. Most Acute attack medications include specific medications, such patients experience reduced ability to function with attacks and as triptans, ergots and dihydroergotamine (DHE), and non-spe- many are bed-bound. Migraines can have multiple triggers such cific medications used for other pain disorders. In selecting acute as food, sleep changes, or hormonal factors.1 Often migraineurs migraine medication, patients need a treatment plan tailored to elect to treat their headaches without physician consultation their headache type. Mild or moderate intensity attacks often using rest or over-the-counter (OTC) medications. Patients who respond to treatment with non-steroidal anti-inflammatory present for evaluation with migraine have usually tried some medications (NSAIDs) or combination medications, while more 12 Practical Neurology February 2009 severe attacks may respond better to specific medications. If the or combination medications more than 10 days a month for initial treatments fail, rescue medication is needed. This review more than three months.11 Frequent opioid and barbiturate use discusses acute evidence-based and practical treatments for are risk factors for the development of CDH,12 and stopping migraine, and specifically focuses on the treatment of intractable these medications can result in increased headache and with- headaches such as status migrainosus. drawal symptoms. MOH requires overuse for at least three months and a history of headaches worsening with the overuse.13 Basic Principles MOH can cause adverse events (AEs) specific to the class of In migraine, there are two basic strategies for treatment of acute medication such as ergotism, constipation, gastrointestinal and headache: step care and stratified care. In the step care model, renal disease, or tardive dyskinesias. Treatment of MOH by with- patients usually progress through a sequence of medications— drawing the offending agent usually improves migraine after a usually starting with a simple analgesic, then perhaps an anti- period of increased headache lasting weeks to months. emetic, and then a specific medication if the initial treatments are Migraineurs should be aware of MOH and keep a headache cal- ineffective.3 This can mean escalating treatment across or within endar (diary) of headaches and acute medication use.14 attacks. Stratified care involves treating attacks based on migraine Frequent migraines or those that do not respond to acute severity. In this model, patients use non-specific medications for agents are an indication for prophylaxis. Preventative medications minimally disabling attacks, and specific are indicated in patients with 1.) attacks medications for severe attacks. more than once a week, 2.) acute med- Compared to step care, stratified care ication use more than two days per improves treatment outcomes,4 improves Compared to week, 3.) impairment of quality of life or quality of life,5 and reduces costs.6 disability despite acute medication use, Early treatment of migraine attacks step care, 4.) complicated migraine conditions improves outcomes. Patients taking such as hemiplegic migraine, and 5.) ad- triptans early, when the pain is still stratified care verse events or contraindications to mild, often have increased pain-free acute medication. For example, patients rates at two hours.7 When taken early, improves with a contraindication to triptans or triptans may prevent the development ergots, such as coronary artery disease, of central sensitization in migraine,8 as treatment may need migraine prophylaxis, as acute manifested clinically by cutaneous allo- agents might not be effective.15 Migraine dynia, which is pain in response to nor- outcomes, prophylaxis is indicated in about one- mally non-painful stimuli. Migraineurs third of all migraineurs, but only three to with cutaneous allodynia are less likely improves quality 13 percent of patients take them.16 to respond to triptans.9 When selecting acute migraine med- of life, and Non-specific Medications ication, individualize the treatment NSAIDs. NSAIDs are effective in the according to the headache characteris- reduces costs. acute treatment of migraine. They may tics. For rapidly escalating and disabling work by suppressing inflammation and attacks, consider injectable medications. preventing and treating central sensiti- Patients with significant nausea or vomiting should use non-oral zation by blocking glial production of prostaglandins. They may medications and antiemetics. Migraineurs with attacks that do also treat non-traditional migraine symptoms, such as neck pain not respond to specific medication (often with frequent urgent and sinus pressure, that are commonly associated with acute physician or emergency room visits) need a rescue treatment. migraine attacks.17 NSAIDs are less likely to cause MOH than Before deciding a treatment is ineffective, patients should treat at other treatments,12 but frequent use can lead to undesired sys- least two attacks. Other strategies include changing the dose, giv- temic AEs such as peptic ulcers or renal disease. Multiple ing a different formulation or route of administration, or adding NSAIDS demonstrate effectiveness in migraine. (Table 1) They a second agent. can be combined with triptans or antiemetics for severe attacks. For patients with frequent headaches, it is important to avoid Opioids. Opioids provide therapeutic benefit in migraine but overuse of acute medication. Medication overuse impacts more are associated with a high risk of abuse and dependency. Opioids migraineurs than patients with other chronic pain disorders10and are most useful in patients with infrequent but disabling is one cause of chronic daily headache (CDH). Medication over- migraine, especially if there are contraindications to specific treat- use headache (MOH) is defined as the use of simple analgesics ments, such as cardiovascular disease or pregnancy. Although AEs more than 15 days per month or using triptans, ergots, opioids may include sedation or confusion, patients might use opioids as February 2009 Practical Neurology 13 Acute Treatment for Migraine Table 1: NSAIDs effective in migraine migraine and relatively well tolerated.23 Contraindications Medication Route Dose (mg) include glaucoma, renal failure, severe hypertension, heart or renal disease and MAO inhibitors. Naproxyn PO 500-1100 Butalbital-containing analgesics include combinations with Indomethacin PO 25-75 acetaminophen or aspirin with caffeine and with or without PR 50 codeine. No clinical trial demonstrates that butalbital, a barbi- turate, adds to the effectiveness of the constituent components, IM 50 and the risk of dependency and MOH is high.24 As with opi- Indomethacin-prochlorperazine-caffeine PR 25-4-75 oids, use of butalbital-containing medication must be moni- Ketoprofen PO 75-150 tored closely and limited to situations when other treatments are ineffective or contraindicated. Piroxicam SL 40 Ketorolac IM 30-60 Specific Medications Triptans. The development and use of triptans, a class of med- IV 15-60 ications specifically designed to treat acute migraine attacks, Ibuprofen PO 200-400 has revolutionized migraine treatment. Triptans are selective Diclofenac PO 50-100 serotonin receptor agonists, and all have high affinity for 5- HT1B and 5-HT1D receptors, with variable activity at the 5- Aspirin PO 650-1000 HT1F receptor.25 Although initial research suggested triptan Aspirin-acetominophen-caffeine PO 250-250-65 effectiveness occurred because of their vasconstrictive proper- Tolfenamic acid PO 200-400 ties, their ability to block the transmission of pain signals from the trigeminal nerve to the TNC and prevent release of inflam- Celecoxib PO 400 matory neuropeptides is more important.26 Triptans are well PO – oral, SL – sublingual, IM – intramuscular, tolerated and effective, with an excellent safety profile and IV- intravenous, PR – suppository without the risk of dependence or addiction seen with barbitu- a rescue medication to avoid the distress of a visit to the emer- rate or opioid medications. Currently seven different triptans gency room. Codeine with acetaminophen is effective in are available for the treatment of migraine. Each triptan has migraine, and other opioids commonly used as different pharmacologic properties; some are available in differ- rescue treatments include fentanyl, hydromorphone, hydro- ent formulations, such as orally disintegrating tablets, nasal codone, methadone, morphine, oxycodone, propoxyphene, and sprays (NS), or subcutaneous injection (SC).27 (Table 2) pentazocine. Meperdine IM and IV is commonly used18 but may Deciding which triptan to utilize is patient-dependant: how cause paradoxical reactions such as seizures. The agonist-antago- they metabolize the medication, headache patterns, and what nist opioid butorphanol may have lower abuse potential and can adverse events they can experience. SC sumatriptan is the most be given IV (2-3mg) or as a nasal spray (NS) for migraine.19 effective and fastest-acting triptan but causes the