Ketorolac in the Treatment of Acute Migraine

A Systematic Review

Erin Taggart, MD (Candidate); Shandra Doran, MD, PhD; Andrea Kokotillo, MD (Candidate); Sandy Campbell, MLS; Cristina Villa-Roel, MD, MSc, PhD (Candidate); Brian H. Rowe, MD, MSc


Headache. 2013;53(2):277-287. 

In This Article

Abstract and Introduction


This systematic review examined the effectiveness of parenteral ketorolac (KET) in acute migraine. Acute migraine headaches are common emergency department presentations, and despite evidence for various treatments, there is conflicting evidence regarding the use of KET. Searches of MEDLINE, EMBASE, Cochrane, CINAHL, and gray literature sources were conducted. Included studies were randomized controlled trials in which KET alone or in combination with abortive therapy was compared with placebo or other standard therapy in adult patients with acute migraine. Two reviewers assessed relevance, inclusion, and study quality independently, and agreement was measured using kappa (k). Weighted mean differences (WMD) and relative risks are reported with 95% confidence intervals (CIs). Overall, the computerized search identified 418 citations and 1414 gray literature citations. From a list of 34 potentially relevant studies (k = 0.915), 8 trials were included, involving over 321 (141 KET) patients. The median quality scores were 3 (interquartile range: 2–4), and two used concealed allocation. There were no baseline differences in 10-point pain scores (WMD = 0.07; 95% CI: −0.39, 0.54). KET and meperidine resulted in similar pain scores at 60 minutes (WMD = 0.31; −0.68, 1.29); however, KET was more effective than intranasal sumatriptan (WMD = −4.07; 95% CI: −6.02 to −2.12). While there was no difference in pain relief at 60 minutes between KET and phenothiazine agents (WMD = 0.82; 95% CI: −1.33 to 2.98), heterogeneity was high (I2 = 70%). Side effect profiles were similar between KET and comparison groups. Overall, KET is an effective alternative agent for the relief of acute migraine headache in the emergency department. KET results in similar pain relief, and is less potentially addictive than meperidine and more effective than sumatriptan; however, it may not be as effective as metoclopramide/phenothiazine agents.


Migraine headache is a common condition, affecting an estimated 6% of men and up to 18% of women.[1] While acute migraine episodes impair the health of patients and are disruptive, they can also result in considerable resource expenditure within health systems.[2,3] Migraineurs frequently present to emergency departments (EDs) for treatment, and headaches are estimated to be one of the most common three ED complaints, comprising up to 5% of all visits.[4] A number of clinical guidelines on the management of acute migraines exist, and they generally recommend treatment with several different treatments, such as triptans, dihydroergotamine (DHE), phenothiazines, or nonsteroidal anti-inflammatory drugs (NSAIDs).[5–7] A comparison of the guidelines found that a consensus has not yet been reached on the most appropriate therapy for acute migraines, resulting in considerable practice variation.[8,9]

Physicians have an array of pharmacological interventions available for use to treat migraines, with one study reporting 36 different drugs used.[4] One such agent is parenteral ketorolac (KET), an NSAID that has high quality evidence (from a randomized controlled trial [RCT]) to recommend its use as an abortive agent in migraine. Anti-inflammatory medications are expected to be beneficial in the treatment of acute migraines, considering that the pathophysiology of migraine is thought to involve an inflammatory component.[10–12] In line with the current evidence and the suspected benefit, reports suggest that KET is used in up to 16% of ED visits for migraine.[4,6] Yet, despite the perceived benefit, recommended use, and frequent administration of parenteral NSAID therapy in migraine, a comprehensive review of parenteral KET is lacking.

The objective of this review was to assess the available evidence on the efficacy and safety of parenteral KET in treating acute migraine headaches in adult patients in the ED.