Tramadol/Acetaminophen for the Treatment of Acute Migraine Pain: Findings of a Randomized, Placebo-Controlled Trial


  • Stephen D. Silberstein MD,

  • Frederick G. Freitag DO,

  • Todd D. Rozen MD,

  • David B. Kudrow MD,

  • David J. Hewitt MD,

  • Donna M. Jordan BSN,

  • Alan C. Fisher DrPH,

  • Norman R. Rosenthal MD,

  • for the CAPSS-223 Investigators

  • From Jefferson Medical College, Philadelphia, PA (Dr. Silberstein); Diamond Headache Clinic, Chicago, IL (Dr. Freitag); Michigan Head-Pain and Neurological Institute, Ann Arbor, MI (Dr. Rozen); California Medical Clinic for Headache, Santa Monica, CA (Dr. Kudrow); Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ (Dr. Hewitt, Ms. Jordan, Dr. Fisher, and Dr. Rosenthal).

Address all correspondence to Dr. Stephen D. Silberstein, Thomas Jefferson University Hospital/Jefferson Headache Center, Gibbon Building, Suite #8130, 111 South 11th Street, Philadelphia, PA 19107-5092.


Objective.—To compare tramadol/acetaminophen (APAP) and placebo for the management of acute migraine pain.

Background.—Tramadol/APAP tablets reduced moderate-to-moderately severe acute pain in controlled studies of other painful conditions.

Methods.—This randomized, double-blind, placebo-controlled, parallel group study enrolled adults with migraine pain as per International Headache Society criteria. Subjects took tramadol/APAP (total dose, 75 mg/650 mg) or placebo for a typical migraine with moderate-to-severe pain. Severity of pain and migraine-related symptoms were recorded before study medication and at 0.5, 1, 2, 3, 4, 6, and 24 hours after study medication.

Results.—Efficacy analyses included 305 subjects (154 tramadol/APAP and 151 placebo). Treatment response was higher for tramadol/APAP than a placebo at 2 hours after dosing (55.8% vs. 33.8%, P < .001) and at every other assessment from 30 minutes (12.3% vs. 6.6%) through 6 hours (64.9% vs. 37.7%) (all P≤ .022). Subjects in the tramadol/APAP group were more likely than those in the placebo group to be pain-free at 2 hours (22.1% vs. 9.3%), 6 hours (42.9% vs. 25.2%), and 24 hours (52.7% vs. 37.9%) (all P≤ .007). Two hours after dosing, moderate-to-severe symptoms that were less common for tramadol/APAP than placebo included photophobia (34.6% vs. 52.2%, P= .003) and phonophobia (34.3% vs. 44.9%, P= .008), but not migraine-related nausea (38.5% vs. 29.4%, P= .681). Treatment-related adverse events included nausea, dizziness, vomiting, and somnolence.

Conclusions.—Tramadol/APAP reduces the severity of pain, photophobia, and phonophobia associated with migraine headache, but does not reduce migraine-associated nausea. Tramadol/APAP might be an appropriate option for the management of moderate-to-severe migraine headache.