Intravenous dexamethasone vs. placebo as adjunctive therapy to reduce the recurrence rate of acute migraine headaches:  A multicenter, double-blinded, placebo-controlled randomized clinical trial

Background:  Because of a proposed inflammatory component to the disease, some physicians prescribe corticosteroids to patients suffering from migraines without much demonstrated efficacy.

Objective:  To determine the efficacy of adjunctive dexamethasone in preventing the recurrence of migraine at 3 and 30 days after presenting at the ED.

Methods:  This was a prospective, multicenter, emergency department-based, randomized, double-blind, placebo-controlled trial.  Inclusion criteria included patients who were 18-65 years of age and was further broken down into migraine with or without aura.  For migraine without aura the criteria included at least 5 prior migraines without aura, the presence of either nausea/vomiting or photophobia/phonophobia, and at least 2 of the following: Unilateral location, pulsating quality, moderate or severe intensity that inhibits daily activity, or aggravated by routine daily activity.  For migraine with aura the criteria included at least 2 prior migraines with aura, and at least one of the following developing within 4 minutes of migraine and lasting no longer than 1 hour: Unilateral visual symptoms, slowly expanding and moving geometric shapes, one-sided numbness or abnormal traveling sensation, one-sided weakness, or speech difficulty.  Exclusion criteria consisted of: A positive pregnancy test, fever, known allergy to steroids, history of gastrointestinal bleeding within the past year, diabetes, another acute neurologic disorder (stroke symptoms, hypertensive emergency, or symptoms to suggest meningitis or infection), suspicion for narcotic-seeking behavior, steroids taken in the past 30 days, or refusal/inability to give informed consent.  The primary measure was the recurrence of migraine headache at 3 and 30 days.  Secondary outcome measures included: Presence of headache at discharge from ED, medication received in ED, and overall ED visit satisfaction.  115 enrolled initially(53 for placebo, 62 for dexamethasone).  The dose of dexamethasone used was 24 mg.  Reported power was 0.8, alpha was 0.05 and per-protocol analysis was used.

Results:  No statistically significant differences were found regarding the primary and secondary objectives.  Three-day follow up:  42.9% (95% CI 29.1%-57.8%) of the placebo group had a migraine recurrence compared to 36.8 % (CI 25.5%-49.9%) of patients in the dexamethasone group (P=0.6776).  ED satisfaction 71.4% with placebo and 71.9% with active drug (P=1.00).  Headache resolution at the ED (35.7% vs. 47.3%) (P=0.305).  Follow up with PCP (42.9% vs. 43.9 %), with neurologist (14.3% vs. 8.8 %) Other HCP (0 vs. 3.5%), No physician follow-up (42.9% vs. 35.1%), Headache returned after leaving ED (42.9% vs. 36.8%).   12/48 dexamethasone patients had a persistent migraine at 3 days that was initially resolved, compared to 6/30 patients in the placebo group.  (2-tailed P-value = 0.7836 with a trend toward placebo).
Thirty-day follow-up:  47.5% of placebo patients had a recurrence of migraine, while 42.9 % of patients in the dexamethasone group did (P=0.682).  Adverse effects included nausea/vomiting, dizziness, mood changes, swelling/weight gain, and muscle cramps.  Dizziness was reported more often after in the dexamethasone group on 3-day follow-up (p=0.0402).

Strengths:  This study uses the gold standard of study designs.  It also uses more than one treatment center.
 
Weaknesses:  The study possessed a smaller sample size than was required to maintain a level of power that would be acceptable for detecting statistical differences.  Consequently, some results appeared to have a large magnitude of difference, but were not statistically different.  The thirty-day outcome measures were not accurate in measuring the long-term effect of a drug that would be fully cleared from the patient in that time.  There was not set protocol for dosage or class of medication given with IV dexamethasone, nor for lifestyle activities that could affect migraine status.  Also, the authors noted that ED recidivism might have been a better primary outcome than their initial measures.  Patient variability in migraine frequency and duration could have been included in inclusion/exclusion criteria to weed out patients with chronic, unresponsive migraine.  Also, several patients had unresolved migraines remaining at 3-day follow up and should not be classified as having recurrent migraine.

Conclusion:  Based on this study alone, it appears that dexamethasone as an adjunctive migraine treatment in the ED is not effective at preventing recurrence of migraine at three and thirty days. However, further studies with more patients, better-controlled variables and better outcome measures may be required to establish true efficacy and other adverse effects.

Donaldson D, Sundermann R, Jackson R, Bastani A. Intravenous dexamethasone vs. placebo as adjunctive therapy to reduce the recurrence rate of acute migraine headaches:  A multicenter, double-blinded, placebo-controlled randomized clinical trial. Am J Emerg Med. 2008 Feb;26(2):124-30.

Prepared by:  Jeremy R. Armentrout, Doctor of Pharmacy Candidate, March 2008
Revised:  March 2008