DALLAS – Acetaminophen, aspirin, and caffeine in combination – the tablet familiarly known as Excedrin – proved an attractive alternative to intravenous prochlorperazine as first-line therapy for uncomplicated acute migraine in the emergency department, in a randomized, prospective, double-blind clinical trial.
"Excedrin worked as well as prochlorperazine in this study and doesn’t require an IV. I think it’s a good choice for acute cephalgia without significant nausea and vomiting," Dr. Kenneth R. Deitch said at the annual meeting of the Society for Academic Emergency Medicine.
Dr. Kenneth Deitch
In this 71-patient study, both therapies provided significant and comparable pain relief at 60 minutes. Restlessness and/or muscle spasms occurred within the first 120 minutes in 10 patients in the prochlorperazine group and in 3 on acetaminophen, aspirin, and caffeine (AAC). At follow-up 24 hours later, roughly 90% of patients in each study arm said they would use their study medication again, according to Dr. Deitch, an emergency medicine physician at Einstein Medical Center, Philadelphia.
All study participants met International Headache Society criteria for migraine or probable migraine. They were randomized to receive 10 mg of prochlorperazine IV in a 2-minute push plus placebo, or two generic AAC tablets, each containing 250 mg of acetaminophen, 250 mg of aspirin, and 65 mg of caffeine, along with a placebo IV.
The primary endpoint was reduction in pain on a 0-100 visual analog scale at 60 minutes post treatment. The mean reduction was 47 points in the prochlorperazine group and 37 points with AAC; the difference was not statistically significant.
If patients reported inadequate pain relief after 60 minutes, the study code was broken and physicians prescribed a rescue medication of their choosing – most often an opiate. Ten patients in each study arm required the use of rescue medication after 60 minutes.
The study initially included an additional 10 patients – 6 in the prochlorperazine arm and 4 in the AAC arm – who demanded opiates or other drugs before the 60-minute mark. Those patients were excluded from the analysis.
Dr. Deitch noted that migraine or presumed migraine annually accounts for several million ED visits. Guidelines vary for treatment of migraine in the ED and don’t rely on a strong evidence base. Oral narcotics are the most frequently prescribed agents, but the International Headache Society does not recommend them as first-line therapy because of their major drawbacks, which include nausea, constipation, and the potential for abuse and overuse. Other guidelines advocate triptans, but they’re not popular with emergency medicine physicians because of the cardiovascular risk profile.
Prochlorperazine – the most commonly prescribed dopamine agonist for acute migraine in the ED – does not have a Food and Drug Administration indication for migraine. The drug’s off-label usage in this setting is well established, however. Randomized trials have demonstrated that prochlorperazine is as effective as are narcotics and may be more effective than sumatriptan. Akathisia and dystonia are common side effects with prochlorperazine, and those adverse effects are often sufficiently severe to require rescue diphenhydramine, which prolongs the ED stay.
AAC (Excedrin) is the only OTC medication with FDA approval for the treatment of migraine. Its side effect profile is better than that of prochlorperazine, yet AAC is rarely used as first-line therapy for acute migraine in the ED. In part, the evidence was lacking. But even with demonstrated efficacy in a randomized head-to-head comparison with prochlorperazine, "Excedrin is an oral medication. Physicians and patients have an expectation that if a headache is bad enough to bring someone into the ED, the patient expects an IV, and we expect to do that for them."
With fairly good evidence of efficacy even in patients with mild to moderate migraine with nausea, the situation may begin to change as the majority of patients who receive Excedrin have pain relief, he said.
Dr. Deitch reported having no financial conflicts of interest with regard to this study, conducted free of commercial support.