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Isometheptene for acute migraine


Clinical bottom line

Clinical bottom line: Based on very limited data of poor validity, isometheptene given alone or in a compound was shown to be more effective than placebo and ergotamine 1 mg plus caffeine. There is insufficient data to draw any firm conclusions about the efficacy and relative efficacy of this drug.

Isometheptene mucate is a drug that may be prescribed for acute migraine treatment. It is either given alone or in a compound called midrin or midrid (isometheptene mucate 65 mg, dichloralphenazone 100 mg, paracetamol 325 mg). Bandolier pulled together the evidence for how effective this drug is for the treatment of acute migraine attacks.

Inclusion criteria were randomised, double blind trials, acute migraine treatment with isometheptene alone or as a combination drug versus a control group in adults, reporting on headache outcomes.

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 isometheptene. There was no restriction to language. Retrieved reports were searched for additional trials. Neither individual authors nor pharmaceutical companies were contacted for unpublished data.


Four randomised double blind trials were found, all conducted in the 1970s. All of the trials had a number of methodological flaws including unclear migraine diagnostic criteria, inadequate baseline measures of pain, inadequate reporting of actual doses of drugs used, inadequate reporting of withdrawals and dropouts. None of the studies are comparable one to another as they use different dosing regimes, outcome measures and differ with respect to number of attacks studied 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.

In two of the three placebo controlled trials, Isometheptene mucate, given at an initial dose of two tablets (130 mg) then titrated to a maximum of 5 to 6 tabs in four hours, provided significantly better pain relief than placebo (Figure). How clinically meaningful this effect is, is debatable. One active controlled trial showed significantly greater relief of pain with an isometheptene compound (isometheptene mucate 65 mg, dichloralphenazone 100 mg, paracetamol 325 mg) than ergotamine 1mg plus caffeine.

Adverse effects

Only two of the trials reported on adverse effects. In both significantly more adverse effects were reported with isometheptene than placebo. None were reported as being serious.

Further reading

  1. Diamond S. Treatment of migraine with isometheptene, acetaminophen, and dichloralphenazone combination: a double blind, crossover trial. Headache 1976; 15:282-7.
  2. Diamond S, Medina JL. Isometheptene - a non ergot drug in the treatment of migraine. Headache 1975; 15:211-3.
  3. Ryan RE. A study of midrin in the symptomatic relief of migraine headache. Headache 1974; 14:33-42.
  4. Treves TA, Streiffler M, Korczyn AD. Naproxen sodium versus ergotamine tartrate in the treatment of acute migraine attacks. Headache 1992; 32:280-2.