Back to Basics? Efficacy of Combination Acetaminophen-Aspirin-Caffeine in Migraine
ABSTRACT & COMMENTARY
Source: Lipton RB, et al. Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain. Arch Neurol 1998;55:210-217.
In population-based epidemiologic studies, lipton and Stewart (Neurology 1993;43 [Suppl 3]:S6-10) observed that two-thirds of migraine sufferers were never diagnosed by a doctor, and most were self medicated with over-the-counter drugs. Despite this unrestricted use of medication, few of these drugs have ever been subjected to well-controlled clinical trials. Lipton and colleagues now report the efficacy results in migraine for the combination pill containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg (Excedrin Extra Strength, Bristol-Myers Squibb Co.).
A total of 1357 patients were randomized into three independent, double-blind, parallel-group, placebo-controlled studies. The treatment dose consisted of two combination pills taken orally for a single migraine attack. At two hours, pain intensity was reduced to mild or none in 59.3% of the 602 treated patients compared to 32.8% of the 618 placebo group (P < 0.001; 95% CI 55-63% for drug, 29-37% for placebo). If "pain free" was used as an outcome measure, then, at six hours, 50.8% of the treated group were headache free compared to 23.5% of the placebo patients (P < 0.001; 95% CI 47-55% for drug, 20-27% for placebo). Other migraine symptoms such as nausea, photophobia, and phonophobia significantly improved after treatment compared to placebo (P < or = 0.01). Adverse effects in the treated group were minimal and included nausea (4.9%), nervousness (4.4%), and dizziness (2.8%).
COMMENTARY
Given the emergence of the new "triptan" class of migraine drug with prescription costs of $15-20 per pill, an inexpensive and effective over-the-counter choice seems not only viable but ironic. However, the current report identifies two important points worth noting. First, the combined studies excluded the most severe migraineurs. These were patients defined as having incapacitating pain requiring bedrest or having extended periods of vomiting. Secondly, the risk of long-term use was not assessed. Though this was not the purpose of the study, it is important to note that the combination of acetaminophen, aspirin, and caffeine confers a potent risk of escalating use and transforming an episodic migraine into a chronic, daily, essentially rebound headache. The critical dose to cause analgesic rebound is not known. The consensus among headache specialists is that both total dose and usage days are important. With respect to acetaminophen and aspirin, 4000 mg/d and not more than three usage days per week are the maximal limits. Nonetheless, in light of the more expensive newer prescription drugs, strictly limited use of a combination analgesic pill proves an effective option for the infrequent migraine sufferer. -jr
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