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Naproxen for acute migraine


Clinical bottom line:

Naproxen is an effective treatment for acute migraine. Most of the trials were methodologically flawed and can only tell us that naproxen works and not how well it works. Naproxen at doses ranging from 750 to 1250 mg/day provided significantly better pain relief than placebo in four placebo controlled studies. The two trials comparing naproxen with ergotamine 2 to 3 mg showed no significant difference between the two drugs.

A systematic review of naproxen was not found so Bandolier pulled together the evidence for this drug for the acute treatment of migraine. Naproxen is an NSAID of proven efficacy for other pain conditions, but does it work for migraine?

Systematic review

  • Date review completed: December 2000
  • Number of trials included: 5 randomised controlled trials
  • Number of patients: 388
  • Control group: active and placebo
  • Main outcomes: Headache severity and duration

Inclusion criteria were: treatment of acute migraine with naproxen by any route; randomised allocation to treatment groups; double-blind design; adult population and headache outcomes.

Search methods

Comprehensive searches of the following databases were made: MEDLINE (1966 to July 2000), EMBASE (1980 to June 2000), Cochrane Library (Issue 3, 2000) and the Oxford Pain Relief Database (1950 to 1994) (Jadad et al., 1996). A series of free text searches were undertaken, using generic and trade names for naproxen. There was no restriction to language. Retrieved reports were searched for additional trials. Neither individual authors nor pharmaceutical companies were contacted for unpublished data.


Five RCTs were found where 225 patients were randomised to naproxen and 190 to placebo ( Table ). One RCT compared naproxen with ergotamine (n=41). All of the trials studied oral naproxen at doses from 750 to 1250 mg. Although trials were of high quality based on criteria that evaluates randomisation, blinding and withdrawals (Jadad et al 1996), they were methodologically flawed in other aspects of trial design. The trials pre-date development of IHS criteria and in three of them it did not state which diagnostic criteria were used. In two of the studies it was unclear when the outcomes were assessed, therefore results may have been for more than one dose of study medication. Since in all trials the study medication was taken as soon as the migraine occurred, it was not clear if all patients had sufficient pain at baseline to effectively measure a difference.

The trials were disparate with respect to dosing regimes, number of attacks studied and outcome measures precluding pooling of data for quantitative analysis. A descriptive summary of each trial is provided in the Table, and a summary of the overall results below.

Four placebo controlled trials were found and all showed significantly better pain relief with naproxen than placebo. Two of these studies also showed a significant reduction in headache duration with naproxen. Two trials reported dichotomous outcomes (Figure).

In one, 5/37 patients reported no or mild pain at two hours with naproxen and 0/37 with placebo. In the other, 44% patients preferred naproxen and 9% placebo. One active controlled trial, and one placebo controlled trial compared naproxen with ergotamine 2 to 3 mg. In both, there was no significant difference between naproxen and ergotamine for reduction in headache severity.

Adverse effects

Overall, there were nine withdrawals due to adverse effects with naproxen, mostly due to gastrointestinal disturbances.

Further reading

Andersson PG, Hinge HH, Johansen O, Andersen CU, Lademann A, Gotzsche PC. Double blind study of naproxen vs placebo in the treatment of acute migraine attacks. Cephalalgia 1989; 9:29-32.

Johnson ES, Ratcliffe DM, Wilkinson M. Naproxen sodium in the treatment of migraine. Cephalalgia 1985; 5:5-10.

Nestvold K. Naproxen and naproxen sodium in acute migraine attacks. Cephalalgia 1986; 6 Supp:81-4.

Sargent JD, Baumel B, Peters K et al. Aborting a migraine attack: naproxen sodium v ergotamine plus caffeine. Headache 1988; 28:263-6.

Treves TA, Streiffler M, Korczyn AD. Naproxen sodium versus ergotamine tartrate in the treatment of acute migraine attacks. Headache 1992; 32:280-2.