Description of the condition

Migraine is a common, disabling headache disorder, affecting about 12% of Western populations, and with considerable social and economic impact. It is more prevalent in women than men (18% versus 6%), and in the age range 30 to 50 years (Hazard 2009; Lipton 2007; Moens 2007).

The International Headache Society (IHS) classifies two major subtypes. Migraine without aura is the most common, and usually more disabling, subtype. It is characterised by attacks lasting 4 to 72 hours that are typically of moderate to severe pain intensity, unilateral, pulsating, aggravated by normal physical activity and associated with nausea and/or photophobia and phonophobia. Migraine with aura is characterised by reversible focal neurological symptoms that develop over a period of 5 to 20 minutes and last for less than 60 minutes, followed by headache with the features of migraine without aura. In some cases the headache may lack migrainous features or be absent altogether (IHS 2004).

A recent large prevalence study in the US found that over half of migraineurs had severe impairment or required bed rest during attacks. Despite this high level of disability and a strong desire for successful treatment, only a proportion of migraine sufferers seek professional advice for the treatment of attacks. The majority were not taking any preventive medication, although one‐third met guideline criteria for offering or considering it. Nearly all (98%) migraineurs used acute treatments for attacks, with 49% using over‐the‐counter (OTC) medication only, 20% using prescription medication, and 29% using both. OTC medication included aspirin, other non‐steroidal anti‐inflammatory drugs (NSAIDs), paracetamol (acetaminophen) and paracetamol with caffeine (Bigal 2008; Diamond 2007; Lipton 2007). Similar findings have been reported from other large studies in France and Germany (Lucas 2006; Radtke 2009).

The significant impact of migraine with regard to pain, disability, social functioning, quality of relationships, emotional well‐being and general health (Edmeads 1993; Osterhaus 1994; Solomon 1997) results in a huge burden for the individual, health services and society (Clarke 1996; Ferrari 1998; Hu 1999; Solomon 1997). The annual US economic burden relating to migraine, including missed days of work and lost productivity, is US$14 billion (Hu 1999). Thus successful treatment of acute migraine attacks not only benefits patients by reducing their disability and improving health‐related quality of life, but also reduces the need for healthcare resources and increases economic productivity (Jhingran 1996; Lofland 1999).

Description of the intervention

Medicines derived from willow bark, which is rich in salicylate, have been used for centuries for treating pain, fever and inflammation. In the mid‐19th century, chemists first synthesised acetylsalicylic acid, and by the end of the century, Bayer had patented and were selling the drug, which they called aspirin, around the world.

Aspirin is used to treat mild to moderate pain, including migraine; inflammatory conditions such as rheumatoid arthritis; and, in low doses, as an antiplatelet agent in cardiovascular disease. It is a potent gastrointestinal irritant, and may cause discomfort, ulcers and bleeding. It may aIso cause tinnitus at high dose, and it is no longer used in children and adolescents, in whom it may cause Reye's syndrome (swelling of the brain that may lead to coma and death). Its use as an analgesic and antipyretic agent has declined, largely due to these adverse events, as newer products have become available. However, in some countries it may be the only drug readily available, and for some conditions, such as migraine, some individuals report it to be an effective and reliable treatment.

In order to establish whether aspirin is an effective analgesic at a specified dose in acute migraine, it is necessary to study its effects in circumstances that permit detection of pain relief. Such studies are carried out in individuals with established pain of moderate to severe intensity, using single doses of the interventions. Participants who experience an inadequate response with either placebo or active treatment are permitted to use rescue medication, and the intervention is considered to have failed in those individuals. In clinical practice, however, individuals would not normally wait until pain is of at least moderate severity, and may take a second dose of medication if the first dose does not provide adequate relief. Once analgesic efficacy is established in studies using single doses in established pain, further studies may investigate different treatment strategies and patient preferences. These are likely to include treating the migraine early while pain is mild, and using a low dose initially, with a second dose if response is inadequate.

How the intervention might work

Aspirin irreversibly inhibits cyclo‐oxygenase enzymes, which are needed for prostaglandin and thromboxane synthesis. Prostaglandins mediate a variety of physiological functions such as maintenance of the gastric mucosal barrier, regulation of renal blood flow, and regulation of endothelial tone. They also play an important role in mediating inflammatory and nociceptive processes. Suppression of prostaglandin synthesis is believed to underlie the analgesic effects of aspirin (Vane 1971).

The efficacy of oral medications is reduced in many migraineurs because of impaired gastrointestinal motility, which is associated with nausea, and because of non‐absorption of the drug due to vomiting (Volans 1974). The addition of an antiemetic may improve outcomes by alleviating the often incapacitating symptoms of nausea and vomiting, and (at least potentially) by enhancing the bioavailability of the co‐administered analgesic. In particular, prokinetic antiemetics such as metoclopramide, which stimulate gastric emptying, may improve outcomes by increasing absorption of the analgesic (in this case, aspirin; Ross‐Lee 1983; Volans 1975). It has been claimed that treatment with metoclopramide alone can reduce pain in severe migraine (Salazar‐Tortolero 2008), but this claim requires further investigation, since metoclopramide has not been shown to be an analgesic in classical pain studies. The present review will seek to determine whether treatment of acute migraine with aspirin plus an antiemetic is in any way superior to treatment with aspirin alone.

Why it is important to do this review

Population surveys show that aspirin is frequently used to treat migraine headaches, but we could find no systematic review of the efficacy of this intervention in adults. It is important to know where this widely available and inexpensive drug fits in the range of therapeutic options for migraine therapy. For many migraineurs, non‐prescription therapies offer convenience, and may be the only therapies available or affordable.