The Relative Efficacy of Meperidine for the Treatment of Acute Migraine: A Meta-analysis of Randomized Controlled Trials

Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
Annals of emergency medicine (Impact Factor: 4.33). 12/2008; 52(6):705-13. DOI: 10.1016/j.annemergmed.2008.05.036
Source: PubMed

ABSTRACT Despite guidelines recommending against opioids as first-line treatment for acute migraine, meperidine is the agent used most commonly in North American emergency departments. Clinical trials performed to date have been small and have not arrived at consistent conclusions about the efficacy of meperidine. We performed a systematic review and meta-analysis to determine the relative efficacy and adverse effect profile of opioids compared with nonopioid active comparators for the treatment of acute migraine.
We searched multiple sources (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and LILACS, emergency and headache medicine conference proceedings) for randomized controlled trials comparing parenteral opioid and nonopioid active comparators for the treatment of acute migraine headache. Our primary outcome was relief of headache. If this was unavailable, we accepted rescue medication use or we transformed visual analog scale change scores by using an established procedure. We grouped studies by comparator: a regimen containing dihydroergotamine, antiemetic alone, or ketorolac. For each study, we calculated an odds ratio (OR) of headache relief and then assessed clinical and statistical heterogeneity for the group of studies. We then pooled the ORs of headache relief with a random-effects model.
From 899 citations, 19 clinical trials were identified, of which 11 were appropriate and had available data. Four trials involving 254 patients compared meperidine to dihydroergotamine, 4 trials involving 248 patients compared meperidine to an antiemetic, and 3 trials involving 123 patients compared meperidine to ketorolac. Meperidine was less effective than dihydroergotamine at providing headache relief (OR=0.30; 95% confidence interval [CI] 0.09 to 0.97) and trended toward less efficacy than the antiemetics (OR=0.46; 95% CI 0.19 to 1.11); however, the efficacy of meperidine was similar to that of ketorolac (OR=1.75; 95% CI 0.84 to 3.61). Compared to dihydroergotamine, meperidine caused more sedation (OR=3.52; 95% CI 0.87 to 14.19) and dizziness (OR=8.67; 95% CI 2.66 to 28.23). Compared to the antiemetics, meperidine caused less akathisia (OR=0.10; 95% CI 0.02 to 0.57). Meperidine and ketorolac use resulted in similar rates of gastrointestinal adverse effects (OR=1.27; 95% CI 0.31 to 5.15) and sedation (OR=1.70; 95% CI 0.23 to 12.72).
Clinicians should consider alternatives to meperidine when treating acute migraine with injectable agents.

Download full-text


Available from: Benjamin W Friedman, Jun 23, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Published data from 1998 revealed that most patients treated for migraine in an emergency department received opioids. Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of non-opioid alternatives. Expert opinion during these years has cautioned against use of opioids for migraine. Our objectives were to compare current frequency of use of various medications for acute migraine in US emergency departments with use of these same medications in 1998 and to identify factors independently associated with opioid use.
    Cephalalgia 06/2014; 35(4). DOI:10.1177/0333102414539055 · 4.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The original Wolff's vascular theory of migraine was supported by the discovery of a class of drugs, the triptans, developed as a selective cephalic vasoconstrictor agents. Even in the neurovascular hypothesis of Moskowitz, that is the neurogenic inflammation of meningeal vessels provoked by peptides released from trigeminal sensory neurons, the vasodilatation provoked by calcitonin gene-related peptide (CGRP) is considered today much more important than oedema. The role of cephalic vasodilatation as a cause of migraine pain was recently sustained by studies showing the therapeutic effect of CGRP receptor antagonists. We discuss the evidence against vasodilatation as migraine pain generator and some findings which we suggest in support of a central (brain) origin of pain.
    The Journal of Headache and Pain 07/2009; 10(5):317-25. DOI:10.1007/s10194-009-0130-6 · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A recent study suggested that results of single-center trials are frequently contradicted when similar trials are performed in multicenter settings. To perform a meta-epidemiologic study to evaluate whether estimates of treatment effect differ between single-center and multicenter randomized, controlled trials (RCTs). MEDLINE was searched via PubMed for meta-analyses of RCTs with binary outcomes that were published between August 2008 and January 2009 and in the first 6 months of 2010 in the 10 leading journals of each medical specialty. One issue of the Cochrane Database of Systematic Reviews was also searched. All individual RCTs included in the meta-analyses were selected. Data were extracted and their quality was assessed by use of the risk of bias tool of the Cochrane Collaboration. The primary outcome was the ratio of odds ratios (ROR), used to quantify the difference in estimated intervention effect between single-center and multicenter RCTs. An ROR less than 1 would indicate larger estimates of the intervention effect in single-center trials. Sensitivity analyses were performed with adjustment for sample size, risk of bias within RCTs, and variance of the log odds ratio to take publication bias into account. Forty-eight meta-analyses were selected, including 421 RCTs (223 were single-center and 198 were multicenter). Single-center RCTs showed a larger intervention effect than did multicenter RCTs (combined ROR, 0.73 [95% CI, 0.64 to 0.83]), with low heterogeneity across individual meta-analyses (I(2) = 12.0%; P = 0.24). Adjustment for sample size yielded consistent results (ROR, 0.85 [CI, 0.74 to 0.97]), as did adjustment for risk of bias within RCTs, such as allocation concealment (ROR, 0.76 [CI, 0.67 to 0.86]), and variance of log odds ratio (ROR, 0.83 [CI, 0.72 to 0.96]). Despite sensitivity analyses, meta-confounding cannot be fully excluded. Single-center RCTs showed larger treatment effects than did multicenter RCTs, a finding that was consistent in all sensitivity analyses. These results suggest that this item should be considered when the results of RCTs and meta-analyses are interpreted. Academic grant Recherche sur la Recherche from the Délégation Interrégionale à la Recherche Clinique (DIRC), Ile de France, Assistance Publique-Hôpitaux de Paris (APHP).
    Annals of internal medicine 07/2011; 155(1):39-51. DOI:10.1059/0003-4819-155-1-201107050-00006 · 16.10 Impact Factor