Wednesday, April 14, 2010

High-Dose Aspirin Relieves Migraine Pain; Review

Research UpdateAspirin 900 mg to 1,000 mg appears to provide significant pain relief within 2 hours for many persons suffering migraine headaches, according to a recent Cochrane review, and may offer advantages over other therapies. However, the potential hazards of this NSAID used too often and/or in higher doses need to be taken into account.

Updating an earlier Cochrane Systematic Review of the literature, researchers at the University of Oxford, UK, identified 13 good-quality clinical trials (n=4,222 participants) that compared aspirin 900 mg or 1,000 mg — alone or in combination with metoclopramide 10 mg (an antiemetic medication) — with placebo or other active comparators, mainly sumatriptan 50 mg or 100 mg [Kirthi et al. 2010]. All active treatments were superior to placebo and high-dose aspirin was found to be beneficial in providing short-term and sustained pain relief.

According to the analysis, migraine pain was reduced from moderate or severe to no pain within 2 hours in approximately 1 in 4 subjects (24%) taking aspirin, compared with about 1 in 10 (11%) taking placebo. Pain was reduced to no worse than mild pain by 2 hours in roughly half of persons taking aspirin (52%) compared with approximately a third taking placebo (32%). Of those experiencing effective headache relief at 2 hours, more patients experienced sustained relief during a full 24 hours with aspirin than with placebo.

Oral sumatriptan 100 mg was somewhat better than aspirin-plus-metoclopramide for pain-free response at 2 hours, but there were no other major differences between aspirin with or without metoclopramide and sumatriptan 50 mg or 100 mg. Adverse events with short-term use were mostly mild and transient, occurring slightly more often with aspirin than placebo, and more often with sumatriptan 100 mg than with aspirin. Migraine-associated symptoms of nausea, vomiting, photophobia (light sensitivity), and phonophobia (sound sensitivity) were reduced with aspirin compared with placebo, and the addition of the antiemetic metoclopramide significantly reduced nausea (p < 0.00006) and vomiting (p = 0.002) compared with aspirin alone.

COMMENTS: Aspirin 1,000 mg plus metoclopramide 10 mg appears to be an effective treatment alternative for acute migraine headaches, and could be of special importance for patients who cannot tolerate sumatriptan (Imitrex®) side effects or otherwise prefer not to use the triptan class of medications. In the U.S., aspirin comes in 325 mg and 500 mg formulations that are relatively economically priced.

Looking more closely at the data, aspirin would not be universally effective: roughly 1 in 8 (NNT=7.7) patients taking high-dose aspirin may experience complete migraine-pain relief and 1 in 5 (NNT=5.0) may have their pain greatly reduced within 2 hours. Although this appears comparable to outcomes with sumatriptan, according to the research, individual patient differences may affect treatment response to either agent. NSAIDs other than aspirin, or combinations such as ibuprofen-plus-acetaminophen, also may be advantageous for some patients; however, as we noted in a prior blogpost [here], there are a number of strong safety concerns with NSAIDs that must be considered if frequent migraine attacks require repeated use.

POSTSCRIPT: Mass media news items are now appearing with statements that misinterpret the main point of this research. For example, one newscaster said, “A review of 13 studies finds aspirin can reduce the pain of migraine within two hours for over 50 percent of people.” This ignores the 32% benefit of placebo effects resulting in diminished pain. The true effect of aspirin is 52%-32%=20% or an NNT=5.0 (benefitting 1 in 5 persons), as we note above. While some might argue that it doesn’t matter if pain relief was due to a combination of placebo and aspirin effects, the placebo effect cannot be counted on when evaluating medication efficacy. [See our previous discussion of placebo effects in pain management.]

REFERENCE: Kirthi V, Derry S, Moore RA, McQuay HJ. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database of Systematic Reviews. 2010;4(CD008041) [abstract here].