The Pathophysiological and Pharmacological Basis of Current Drug Treatment of Migraine Headache

Doodipala Samba Reddy


Expert Rev Clin Pharmacol. 2013;6(3):271-288. 

In This Article

Symptomatic Treatment of Migraine: Mild-to-Moderate Migraine

Symptomatic treatment of migraine (STM) can be nonspecific such as NSAIDs, acetaminophen, isometheptene preparations, narcotics and tramadol. Narcotics should not be used as first line therapy, but may be preferable for some patients with infrequent migraine if this is the most effective treatment and there is no indication of escalation of dose or overuse. STM agents are pain relievers that are not specific for migraine. Analgesics and NSAID combinations are frequently used to treat mild-to-moderate acute migraine (Table 2). Aspirin and acetaminophen alone have been shown to be effective for treatment of mild migraine.[62] They are often marketed in combinations with other agents. Acetaminophen and other NSAIDs are useful but not approved by the US FDA for migraine. Aspirin may benefit some migraine patients through its anti-inflammatory action. The US FDA-approved OTC analgesics used in the management of migraine include ibuprofen (Advil® Migraine, Pfizer, NY, USA; Motrin® Migraine, McNeil Consumer Healthcare, PA, USA) and acetaminophen/aspirin/caffeine combinations (Excedrin® Migraine, Novartis, Basel, Switzerland). Naproxen has been approved for migraine in combination with sumatriptan (Treximet®, GlaxoSmithKline). NSAID combinations have been reported to be effective in the abortive therapy of mild-to-moderate migraine. These agents inhibit lipoxygenase and cyclooxygenase enzymes that catalyze the production of prostaglandins, and thereby interfere with the neurogenic inflammation associated with migraine pathogenesis.

All FDA-approved migraine treatments are approved only for adults. No migraine products have officially been approved for use in children. Other types of drugs, including opioids and barbiturates, are sometimes prescribed off-label for migraine treatment. Opioids and barbiturates have not been approved by the FDA for migraine relief and they can be addictive. Barbiturate combinations are generally indicated for treatment of tension headache. Butalbital and aspirin/caffeine (Fiorinal®, Watson Pharma, NJ, USA) and butalbital and acetaminophen/caffeine (Fioricet®, Watson Pharma) are prescription NSAID combination drugs used in the management of migraine. However, they are not FDA indicated for migraine. Butalbital has not been shown to be effective for migraine in controlled trials.

Metoclopramide (Reglan) taken promptly after the onset of symptoms can enhance absorption of NSAIDs and triptans by increasing gastric motility and it may prevent the nausea associated with migraine attacks. Metoclopramide and other antiemetic drugs, such as domperidone (Motilium®, Janssen Pharmaceuticals, NJ, USA), may enhance the intestinal absorption of antimigraine drugs.