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A prospective double-blind study of nasal sumatriptan versus IV ketorolac in migraine
A Prospective Double-Blind Study of Nasal Sumatriptan Versus IV Ketorolac in Migraine JOHN T. MEREDITH, MD, SCOTT WAIT, AND KORI L. BREWER, PHD We conducted a study to compare the efficacy in migraine headache of nasal sumatriptan and intravenous ketorolac. The study was a prospective, double-blind study done with a convenience sample of 29 patients presenting to the emergency department (ED) with acute migraine. Patients received either 20 mg of nasal sumatriptan or 30 mg of intravenous ketorolac. Patients scored the severity of their headache on a 100-mm visual analog scale (VAS) of pain prior to medication, and again 1 hour after medication. Differences between initial and 1-hour scores were analyzed. Before treatment, no difference existed between the groups in the intensity of headache. One hour after medication, the sumatriptan group had a decrease in pain score of 22.937 mm and the ketorolac group a decrease of 71.462 mm on the VAS. The decrease in pain score with ketorolac was significantly greater than that with sumatriptan (P < 0.001). The study therefore showed that both sumatriptan and ketorolac effectively reduced the pain associated with acute migraine headache, but that intravenous ketorolac produced a greater reduction in pain than did nasal sumatriptan. (Am J Emerg Med 2003;21:173-175. © 2003 Elsevier Inc. All rights reserved.)
Migraine headache is a common and often disabling affliction that affects 11.3 million people in the United States.1 Studies note that 17.6% of all females and 5.7% of all males will have at least one migraine headache of moderate to severe intensity each year,1 with the overall prevalence of the condition ranging from 5.3% to 19% in males and 11% to 28% in females.1-3 Furthermore, the annual cost of migraine headache is estimated at $13 billion from missed workdays and impaired work function.4 For the emergency physician, migraine headache is a common chief complaint, with up to 2.5% of patients presenting with headache.5 Of importance to the emergency physician (EP) is a positive association between migraine and the risk of motor-vehicle crashes—an association accounting for as many as 1 in 20 motor-vehicle driver injuries.6 Most persons with migraine who experience mild to moderate headache will successfully self-medicate as outpatients. However, the emergency department (ED) often becomes the primary source of treatment for moderate to severe migraine headache. Various medications have been recommended as therapy in the ED setting. However, the choice of medication is often based on the EP’s personal
and on patient preferences. What may work with one patient may not be an optimal therapy for another patient. Both nasal sumatriptan and intravenous ketorolac relieve migraine pain.7-10 Nevertheless, the effectiveness of nasal sumatriptan and intravenous ketorolac have not been compared in the treatment of moderate to severe migraine headache in the ED setting. METHODS Study Design We performed a prospective, double-blind comparison study of nasal sumatriptan v intravenous ketorolac with a convenience sample of patients presenting to the ED with moderate to severe migraine headache. The study was approved by the University and Medical Center Institutional Review Board of East Carolina University. Study Population The study setting was a university-based, tertiary care ED with an annual census of 55,000 patient visits. Inclusion criteria consisted of patients ⬎18 and ⬍65 years of age with a history of migraine headache, who were diagnosed as having migraine headache by the attending EP. Modified International Headache Society (IHS) criteria for migraine headache without aura were used to define migraine headache.11 Exclusion criteria included known allergy to sumatriptan or ketorolac, active peptic ulcer disease; current use of an ergotamine-containing medication, monoamine oxidase inhibitor, or antidepressant; hemiplegic or basilar migraine headache; renal impairment or dialysis dependence; and menstruation, pregnancy, or nursing. Patients who had taken sumatriptan or nonsteroidal antiinflammatory medication prior to arrival were excluded. Patients in whom there was suspicion of life-threatening illness such as acute intracranial hemorrhage, meningitis, encephalopathy, or intracranial cerebral vascular occlusion, or who did not have someone to drive them after discharge, were also excluded. Experimental Protocol
From the Department of Emergency Medicine, The Brody School of Medicine at East Carolina University, Greenville, NC. Received March 2, 2002; accepted April 6, 2002. Address reprints to Kori L. Brewer, PhD, The Brody School of Medicine at East Carolina University, Department of Emergency Medicine, Division of Research, Physician’s Quadrangle, Building M, Greenville NC 27858. Phone: 252-816-2158 Fax: 252-816-2655 E-mail: [email protected]. Key Words: Nasal sumatriptan, intravenous ketorolac, migraine headache. © 2003 Elsevier Inc. All rights reserved. 0735-6757/03/2103-0002$30.00/0 doi:10.1016/S0735-6757(02)42256-5
For subjects meeting the inclusion criteria and consenting to enrollment in the study, an intravenous line of normal saline was established at a rate sufficient to open the infusion vein. Before medication, subjects were randomly assigned to received sumatriptan at 20-mg via nasal administration, or ketorolac at 30-mg via intravenous administration. Randomization to either of these arms of the study was done by a computer-generated random-number program for participant assignment. Prior to treatment, participants ranked their headache pain on a horizontal visual analog scale 173
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AMERICAN JOURNAL OF EMERGENCY MEDICINE ■ Volume 21, Number 3 ■ May 2003
(VAS) of 100 mm. The left endpoint of this VAS was “no pain” and the right endpoint was “pain as bad as it could possibly be.” The treating physician and nurse were blinded to which medication the patient was receiving. Patients receiving nasal sumatriptan also received 10 cc of normal saline intravenously. Patients receiving intravenous ketorolac also received a control consisting of nasal spray without active ingredients. One hour after medication, each patient ranked his/her headache pain on a separate VAS. The physician and study participant were then unblinded. Six participants required rescue medication: 4 in the sumatriptan and 2 in the ketorolac arm. Data Analysis Pain ratings were recorded by measuring the length of the VAS to the left of the mark made by the patient. A measurement was made by each of two independent, blinded individuals, with the average of the two measurements used for analysis. Data were then uncoded and sorted into groups for sumatriptan (n ⫽ 16) and ketorolac (n ⫽ 13), each containing pre- and posttreatment pain scores. Repeated measures analysis of variance (RMANOVA) was used to compare pain scores across the four groups and determine whether any significant differences existed. Fisher’s product of least-squares differences was then used to identify which groups differed from the others. Power analysis was used to determine the adequacy of the sample size used. RESULTS Twenty-nine patients were included in the study, of whom 13 received intravenous ketorolac and 16 nasal sumatriptan. The participants consisted of 4 males (13.8%) and 25 females (86.2%), with a mean age of 33 years (18-54 years) for those receiving intravenous ketorolac and a mean age of 34 years (19-56 years) for those receiving nasal sumatriptan. Before administration of the study medications, patients who would receive sumatriptan had a mean pain score of 84.625 mm (SD ⫽ ⫾ 18.103 mm), and patients who would receive ketorolac had a mean pain score of 92.385 mm (SD ⫽ ⫾ 10.943). One hour after sumatriptan administration, the mean pain score for this group was decreased significantly to 61.688 mm (SD ⫽ ⫾ 35.107 mm; power ⫽ 80-90% at P ⱕ .05). One hour after ketorolac administration, the mean pain score had decreased significantly to 20.923 mm (SD ⫽ ⫾ 17.255 mm; power ⫽ 95% at P ⱕ .05). The pain reduction was greater in those patients receiving intravenous ketorolac than in those receiving nasal sumatriptan (95% power at P ⱕ .05). (Fig 1). DISCUSSION Patients with migraine headache, as defined by modified IHS criteria, had significant pain relief with both nasal sumatriptan and intravenous ketorolac at 1 hour after medication administration. Intravenous ketorolac was superior to nasal sumatriptan for pain relief in this study. Outpatient management is the preferred method for treating acute migraine headache, and consists of nonsteroidal antiinflammatory drugs (NSAIDs), dopamine antagonists, serotonin agonists, opioids, local anesthetics, and steroids.
FIGURE 1. Mean patient-reported pain ratings before and after treatment with either nasal sumatriptan or intravenous ketorolac (error bars represent SEM). Both treatments were effective at reducing pain scores associated with migraine. However, ketorolac reduced pain scores significantly more than did sumatriptan. Asterisk indicates a significant change from pretreatment pain scores. Crosses indicate a significant difference from all other groups.
Nevertheless, a significant percentage of patients with migraine headaches present to the ED.5 Optimal therapy would be one in which the acute onset of headache is relieved along with associated symptoms, and the rebound or persistence of headache is relieved for several hours. The recent introduction of nasal sumatriptan for the treatment of migraine headache has expanded the therapeutic options available to the EP for treating severe and debilitating migraine headaches.7,8 Sumatriptan is a selective serotonin-1 (5-hydroxytryptamine1) receptor agonist, and is particularly useful in the treatment of patients whose associated nausea and vomiting preclude oral therapy or who prefer not to receive intramuscular or intravenous medications. In placebo-controlled clinical trials, nasal sumatriptan has been shown to be more effective than placebo in resolving or reducing migraine pain.7,8,12 Nasal sumatriptan is generally well tolerated, with the most frequent side effect being a bitter taste in the back of the mouth, which occurs in 13.5% to 24.5% of patients.14 Other frequent side effects include nausea and vomiting in 11% to 13.5% of patients and nasal or sinus discomfort in 2.5% to 3.8% of patients.7,8,13,14 Serious side effects occur in about 0.14% of patients taking sumatriptan,13 with the most serious of these effects being peripheral and cardiac ischemia in patients with peripheral vascular disease or coronary artery disease. It is important to note that up to 33% of patients receiving nasal sumatriptan have migraine recurrences within 24 hours.7,8 Ketorolac, a NSAID with cyclooxgenase-inhibitory activity, has also been shown to be effective in treating the pain associated with severe migraine headache.9,15-17 Parental ketorolac has a comparable analgesic effect to that of meperidine, a potent narcotic.15 Additionally, ketorolac has been shown to be as effective as prochlorperazine in the treatment of migraine.9 One advantage of ketorolac is the lack of significant sedation. In appropriate patients, ketorolac is generally well tolerated, and side effects with a single dose are very uncommon.18 In fact, ketorolac has signifi-
MEREDITH, WAIT, AND BREWER ■ NASAL SUMATRIPTAN v INTRAVENOUS KETOROLAC IN MIGRAINE
cantly fewer side effects than sedatives, narcotics, and antiemetic medications.18 A previous study suggested that the effectiveness of ketorolac, when assessed 1 hour after administration, can predict the patient’s treatment response.16 As with other NSAIDs, ketorolac should not be given to patients with active peptic ulcer disease, renal insufficiency, NSAID hypersensitivity, those who are pregnant or nursing, elderly patients, or patients with bleeding disorders. A disadvantage of ketorolac is that it is ineffective in treating the nausea and vomiting that often accompany migraine headache. When outpatient management has been unsuccessful, the ED often becomes the primary source of medical care for patients with migraine. Care in the ED allows abortive treatment of an acute migraine without accompaniment by drug dependency or toxicity, as well as the determination of severe comorbid, neurologic, or medical illnesses, and the evaluation of coexisting psychiatric illnesses.19 However, few properly constructed trials that would allow the determination of optimal migraine therapy in the ED have been completed.11 Although intravenous ketorolac and nasal sumatriptan have both been shown to be effective in abortive migraine therapy, the present study is the first to examine the relative effectiveness of these two therapies. Study Limitations Our study had several limitations that are consistent with those of other studies of its kind. No follow-up of participants was conducted. Follow-up at least 48 hours after ED discharge, to document headache reoccurence, medication side effects, and return to another medical facility, would be useful. However, review of the medical records of the patients in this study revealed no return visits to the ED within a 48-hour window. This review was not inclusive for follow up visits to other medical facilities or private physician offices. In non-ED-based studies of nasal sumatriptan, an endpoint of 2 hours after medication is used. The 1-hour endpoint selected in this study is typical of studies based in the ED comparing different treatments of migraine, and is appropriate on the basis of evidence that both nasal sumatriptan and intravenous ketorolac have their onset of action within 15 minutes.8 The findings in our study represent a convenience sample of patients. A large number of study candidates refused enrollment, stating that they simply wanted their migraine to be quickly relieved. A number of candidates listed ketorolac as causing mediation allergy. A placebo control group was not used because of ethical considerations involved in treating a patient seeking pain relief. How these limitations biased our study is not quantifiable. A review of previous studies of this nature reveals a consistency of these limitations.9,16,20,21 Conclusion Optimal migraine therapy consists of a treatment protocol that is safe, rapid in onset, and free of side effects, and which allows for consistent relief without recurrence. Unfortunately, the optimal therapeutic regimen for acute mi-
175
graine in the ED has not been determined. What is required in the future is a standardized methodology evaluating all medications used in the ED setting for treating acute migraine headache.10 Such a standardized methodology and medication trial could address the limitations in our study and other ED- based medication trials of migraine therapy. REFERENCES 1. Stewart WF, Lipton RB, Celentano DD, Reed ML: Prevalence of migraine headache in the United States: relation to age, income, race, and other sociodemographic factors. JAMA 1992;267:64-69 2. Deubner DC: An epidemiologic study of migraine and headache in 10 –20 year olds. Headache 1997;17:173-180 3. D’Allesandro R, Benassi G, Lenzi PL, et al: Epidemiology of headache in the Republic of San Marino. J Neurol Neurosurg Psychiatry 1998;51:21-27 4. Hu XH, Markson LE, Lipton RB, et al: Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818 5. Dhopesh V, Anwar R, Herring C: A retrospective assessment of emergency department patients with complaint of headache. Headache 1979;19:37-42 6. Norton R, Vander Horn S, Roberts I, et al: Migraine: a risk factor for motor vehicle driver injury? Accid Anal Prev 1997;29:699701 7. Diamond S, Elkind A, Jackson T, et al: Multiple attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine. Arch Fam Med 1998;7:234-240 8. Ryan R, Elkind A, Baker CC, et al: Sumatriptan nasal spray for the acute treatment of migraine: results of two clinical studies. Neurology 1997;49:1225-1230 9. Seim MB, March JA, Dunn KA: Intravenous ketorolac vs intravenous prochlorperazine for the treatment of migraine headaches. Acad Emerg Med 1998;5:573-576 10. Ducharme J: Canadian Association of Emergency Physicians guidelines for the acute management of migraine headache. J Emerg Med 1999;17:137-144 11. Headache Classification Committee of the International Headache Society: Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. CMAJ 1997;156: 1273-1287 12. The Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group: A placebo-controlled study of intranasal sumatriptan for the acute treatment of migraine. Eur Neurol 1991; 31:332-338 13. Perry CM, Markham A: Sumatriptan: an updated review of its use in migraine. Drugs 1998;55:889-922 14. Weitzel KW, Thomas ML, Small RE, Goode JVR: Migraine: a comprehensive review of new treatment options. Pharmacotherapy 1999;19:957-973 15. Larkin GL, Prescott JE: A randomized, double-blind, comparative study of the efficacy of ketorolac tromethamine versus meperidine in the treatment of severe migraine. Ann Emerg Med 1992;21: 919-924 16. Davis CP, Torre PR, Schafer NC, et al: Ketorolac as a rapid and effective treatment of migraine headache: evaluations by patients. Am J Emerg Med 1993;11:573-575 17. Harden RN, Carter TD, Gilman CS, et al: Ketorolac in acute headache management. Headache 1991;31:463-464 18. Buckley MM, Brogden RN: Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1990;39:86-109 19. Saper JR: Diagnosis and symptomatic treatment of migraine. Headache 1997;37suppl 1:S1-S14 20. Davis CP, Torre PR, Williams C, et al: Ketorolac versus meperidine-plus- promethazine treatment of migraine headache: evaluations by patients. Am J Emerg Med 1995;13:146-150 21. Harden RN, Gracely RH, Carter T, Warner G: The placebo effect in acute headache management: ketorolac, meperidine, and saline in the emrgency department. Headache 1996;36:352-356
Migraine headache is a common and often disabling affliction that affects 11.3 million people in the United States.1 Studies note that 17.6% of all females and 5.7% of all males will have at least one migraine headache of moderate to severe intensity each year,1 with the overall prevalence of the condition ranging from 5.3% to 19% in males and 11% to 28% in females.1-3 Furthermore, the annual cost of migraine headache is estimated at $13 billion from missed workdays and impaired work function.4 For the emergency physician, migraine headache is a common chief complaint, with up to 2.5% of patients presenting with headache.5 Of importance to the emergency physician (EP) is a positive association between migraine and the risk of motor-vehicle crashes—an association accounting for as many as 1 in 20 motor-vehicle driver injuries.6 Most persons with migraine who experience mild to moderate headache will successfully self-medicate as outpatients. However, the emergency department (ED) often becomes the primary source of treatment for moderate to severe migraine headache. Various medications have been recommended as therapy in the ED setting. However, the choice of medication is often based on the EP’s personal
and on patient preferences. What may work with one patient may not be an optimal therapy for another patient. Both nasal sumatriptan and intravenous ketorolac relieve migraine pain.7-10 Nevertheless, the effectiveness of nasal sumatriptan and intravenous ketorolac have not been compared in the treatment of moderate to severe migraine headache in the ED setting. METHODS Study Design We performed a prospective, double-blind comparison study of nasal sumatriptan v intravenous ketorolac with a convenience sample of patients presenting to the ED with moderate to severe migraine headache. The study was approved by the University and Medical Center Institutional Review Board of East Carolina University. Study Population The study setting was a university-based, tertiary care ED with an annual census of 55,000 patient visits. Inclusion criteria consisted of patients ⬎18 and ⬍65 years of age with a history of migraine headache, who were diagnosed as having migraine headache by the attending EP. Modified International Headache Society (IHS) criteria for migraine headache without aura were used to define migraine headache.11 Exclusion criteria included known allergy to sumatriptan or ketorolac, active peptic ulcer disease; current use of an ergotamine-containing medication, monoamine oxidase inhibitor, or antidepressant; hemiplegic or basilar migraine headache; renal impairment or dialysis dependence; and menstruation, pregnancy, or nursing. Patients who had taken sumatriptan or nonsteroidal antiinflammatory medication prior to arrival were excluded. Patients in whom there was suspicion of life-threatening illness such as acute intracranial hemorrhage, meningitis, encephalopathy, or intracranial cerebral vascular occlusion, or who did not have someone to drive them after discharge, were also excluded. Experimental Protocol
From the Department of Emergency Medicine, The Brody School of Medicine at East Carolina University, Greenville, NC. Received March 2, 2002; accepted April 6, 2002. Address reprints to Kori L. Brewer, PhD, The Brody School of Medicine at East Carolina University, Department of Emergency Medicine, Division of Research, Physician’s Quadrangle, Building M, Greenville NC 27858. Phone: 252-816-2158 Fax: 252-816-2655 E-mail: [email protected]. Key Words: Nasal sumatriptan, intravenous ketorolac, migraine headache. © 2003 Elsevier Inc. All rights reserved. 0735-6757/03/2103-0002$30.00/0 doi:10.1016/S0735-6757(02)42256-5
For subjects meeting the inclusion criteria and consenting to enrollment in the study, an intravenous line of normal saline was established at a rate sufficient to open the infusion vein. Before medication, subjects were randomly assigned to received sumatriptan at 20-mg via nasal administration, or ketorolac at 30-mg via intravenous administration. Randomization to either of these arms of the study was done by a computer-generated random-number program for participant assignment. Prior to treatment, participants ranked their headache pain on a horizontal visual analog scale 173
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AMERICAN JOURNAL OF EMERGENCY MEDICINE ■ Volume 21, Number 3 ■ May 2003
(VAS) of 100 mm. The left endpoint of this VAS was “no pain” and the right endpoint was “pain as bad as it could possibly be.” The treating physician and nurse were blinded to which medication the patient was receiving. Patients receiving nasal sumatriptan also received 10 cc of normal saline intravenously. Patients receiving intravenous ketorolac also received a control consisting of nasal spray without active ingredients. One hour after medication, each patient ranked his/her headache pain on a separate VAS. The physician and study participant were then unblinded. Six participants required rescue medication: 4 in the sumatriptan and 2 in the ketorolac arm. Data Analysis Pain ratings were recorded by measuring the length of the VAS to the left of the mark made by the patient. A measurement was made by each of two independent, blinded individuals, with the average of the two measurements used for analysis. Data were then uncoded and sorted into groups for sumatriptan (n ⫽ 16) and ketorolac (n ⫽ 13), each containing pre- and posttreatment pain scores. Repeated measures analysis of variance (RMANOVA) was used to compare pain scores across the four groups and determine whether any significant differences existed. Fisher’s product of least-squares differences was then used to identify which groups differed from the others. Power analysis was used to determine the adequacy of the sample size used. RESULTS Twenty-nine patients were included in the study, of whom 13 received intravenous ketorolac and 16 nasal sumatriptan. The participants consisted of 4 males (13.8%) and 25 females (86.2%), with a mean age of 33 years (18-54 years) for those receiving intravenous ketorolac and a mean age of 34 years (19-56 years) for those receiving nasal sumatriptan. Before administration of the study medications, patients who would receive sumatriptan had a mean pain score of 84.625 mm (SD ⫽ ⫾ 18.103 mm), and patients who would receive ketorolac had a mean pain score of 92.385 mm (SD ⫽ ⫾ 10.943). One hour after sumatriptan administration, the mean pain score for this group was decreased significantly to 61.688 mm (SD ⫽ ⫾ 35.107 mm; power ⫽ 80-90% at P ⱕ .05). One hour after ketorolac administration, the mean pain score had decreased significantly to 20.923 mm (SD ⫽ ⫾ 17.255 mm; power ⫽ 95% at P ⱕ .05). The pain reduction was greater in those patients receiving intravenous ketorolac than in those receiving nasal sumatriptan (95% power at P ⱕ .05). (Fig 1). DISCUSSION Patients with migraine headache, as defined by modified IHS criteria, had significant pain relief with both nasal sumatriptan and intravenous ketorolac at 1 hour after medication administration. Intravenous ketorolac was superior to nasal sumatriptan for pain relief in this study. Outpatient management is the preferred method for treating acute migraine headache, and consists of nonsteroidal antiinflammatory drugs (NSAIDs), dopamine antagonists, serotonin agonists, opioids, local anesthetics, and steroids.
FIGURE 1. Mean patient-reported pain ratings before and after treatment with either nasal sumatriptan or intravenous ketorolac (error bars represent SEM). Both treatments were effective at reducing pain scores associated with migraine. However, ketorolac reduced pain scores significantly more than did sumatriptan. Asterisk indicates a significant change from pretreatment pain scores. Crosses indicate a significant difference from all other groups.
Nevertheless, a significant percentage of patients with migraine headaches present to the ED.5 Optimal therapy would be one in which the acute onset of headache is relieved along with associated symptoms, and the rebound or persistence of headache is relieved for several hours. The recent introduction of nasal sumatriptan for the treatment of migraine headache has expanded the therapeutic options available to the EP for treating severe and debilitating migraine headaches.7,8 Sumatriptan is a selective serotonin-1 (5-hydroxytryptamine1) receptor agonist, and is particularly useful in the treatment of patients whose associated nausea and vomiting preclude oral therapy or who prefer not to receive intramuscular or intravenous medications. In placebo-controlled clinical trials, nasal sumatriptan has been shown to be more effective than placebo in resolving or reducing migraine pain.7,8,12 Nasal sumatriptan is generally well tolerated, with the most frequent side effect being a bitter taste in the back of the mouth, which occurs in 13.5% to 24.5% of patients.14 Other frequent side effects include nausea and vomiting in 11% to 13.5% of patients and nasal or sinus discomfort in 2.5% to 3.8% of patients.7,8,13,14 Serious side effects occur in about 0.14% of patients taking sumatriptan,13 with the most serious of these effects being peripheral and cardiac ischemia in patients with peripheral vascular disease or coronary artery disease. It is important to note that up to 33% of patients receiving nasal sumatriptan have migraine recurrences within 24 hours.7,8 Ketorolac, a NSAID with cyclooxgenase-inhibitory activity, has also been shown to be effective in treating the pain associated with severe migraine headache.9,15-17 Parental ketorolac has a comparable analgesic effect to that of meperidine, a potent narcotic.15 Additionally, ketorolac has been shown to be as effective as prochlorperazine in the treatment of migraine.9 One advantage of ketorolac is the lack of significant sedation. In appropriate patients, ketorolac is generally well tolerated, and side effects with a single dose are very uncommon.18 In fact, ketorolac has signifi-
MEREDITH, WAIT, AND BREWER ■ NASAL SUMATRIPTAN v INTRAVENOUS KETOROLAC IN MIGRAINE
cantly fewer side effects than sedatives, narcotics, and antiemetic medications.18 A previous study suggested that the effectiveness of ketorolac, when assessed 1 hour after administration, can predict the patient’s treatment response.16 As with other NSAIDs, ketorolac should not be given to patients with active peptic ulcer disease, renal insufficiency, NSAID hypersensitivity, those who are pregnant or nursing, elderly patients, or patients with bleeding disorders. A disadvantage of ketorolac is that it is ineffective in treating the nausea and vomiting that often accompany migraine headache. When outpatient management has been unsuccessful, the ED often becomes the primary source of medical care for patients with migraine. Care in the ED allows abortive treatment of an acute migraine without accompaniment by drug dependency or toxicity, as well as the determination of severe comorbid, neurologic, or medical illnesses, and the evaluation of coexisting psychiatric illnesses.19 However, few properly constructed trials that would allow the determination of optimal migraine therapy in the ED have been completed.11 Although intravenous ketorolac and nasal sumatriptan have both been shown to be effective in abortive migraine therapy, the present study is the first to examine the relative effectiveness of these two therapies. Study Limitations Our study had several limitations that are consistent with those of other studies of its kind. No follow-up of participants was conducted. Follow-up at least 48 hours after ED discharge, to document headache reoccurence, medication side effects, and return to another medical facility, would be useful. However, review of the medical records of the patients in this study revealed no return visits to the ED within a 48-hour window. This review was not inclusive for follow up visits to other medical facilities or private physician offices. In non-ED-based studies of nasal sumatriptan, an endpoint of 2 hours after medication is used. The 1-hour endpoint selected in this study is typical of studies based in the ED comparing different treatments of migraine, and is appropriate on the basis of evidence that both nasal sumatriptan and intravenous ketorolac have their onset of action within 15 minutes.8 The findings in our study represent a convenience sample of patients. A large number of study candidates refused enrollment, stating that they simply wanted their migraine to be quickly relieved. A number of candidates listed ketorolac as causing mediation allergy. A placebo control group was not used because of ethical considerations involved in treating a patient seeking pain relief. How these limitations biased our study is not quantifiable. A review of previous studies of this nature reveals a consistency of these limitations.9,16,20,21 Conclusion Optimal migraine therapy consists of a treatment protocol that is safe, rapid in onset, and free of side effects, and which allows for consistent relief without recurrence. Unfortunately, the optimal therapeutic regimen for acute mi-
175
graine in the ED has not been determined. What is required in the future is a standardized methodology evaluating all medications used in the ED setting for treating acute migraine headache.10 Such a standardized methodology and medication trial could address the limitations in our study and other ED- based medication trials of migraine therapy. REFERENCES 1. Stewart WF, Lipton RB, Celentano DD, Reed ML: Prevalence of migraine headache in the United States: relation to age, income, race, and other sociodemographic factors. JAMA 1992;267:64-69 2. Deubner DC: An epidemiologic study of migraine and headache in 10 –20 year olds. Headache 1997;17:173-180 3. D’Allesandro R, Benassi G, Lenzi PL, et al: Epidemiology of headache in the Republic of San Marino. J Neurol Neurosurg Psychiatry 1998;51:21-27 4. Hu XH, Markson LE, Lipton RB, et al: Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818 5. Dhopesh V, Anwar R, Herring C: A retrospective assessment of emergency department patients with complaint of headache. Headache 1979;19:37-42 6. Norton R, Vander Horn S, Roberts I, et al: Migraine: a risk factor for motor vehicle driver injury? Accid Anal Prev 1997;29:699701 7. Diamond S, Elkind A, Jackson T, et al: Multiple attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine. Arch Fam Med 1998;7:234-240 8. Ryan R, Elkind A, Baker CC, et al: Sumatriptan nasal spray for the acute treatment of migraine: results of two clinical studies. Neurology 1997;49:1225-1230 9. Seim MB, March JA, Dunn KA: Intravenous ketorolac vs intravenous prochlorperazine for the treatment of migraine headaches. Acad Emerg Med 1998;5:573-576 10. Ducharme J: Canadian Association of Emergency Physicians guidelines for the acute management of migraine headache. J Emerg Med 1999;17:137-144 11. Headache Classification Committee of the International Headache Society: Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. CMAJ 1997;156: 1273-1287 12. The Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group: A placebo-controlled study of intranasal sumatriptan for the acute treatment of migraine. Eur Neurol 1991; 31:332-338 13. Perry CM, Markham A: Sumatriptan: an updated review of its use in migraine. Drugs 1998;55:889-922 14. Weitzel KW, Thomas ML, Small RE, Goode JVR: Migraine: a comprehensive review of new treatment options. Pharmacotherapy 1999;19:957-973 15. Larkin GL, Prescott JE: A randomized, double-blind, comparative study of the efficacy of ketorolac tromethamine versus meperidine in the treatment of severe migraine. Ann Emerg Med 1992;21: 919-924 16. Davis CP, Torre PR, Schafer NC, et al: Ketorolac as a rapid and effective treatment of migraine headache: evaluations by patients. Am J Emerg Med 1993;11:573-575 17. Harden RN, Carter TD, Gilman CS, et al: Ketorolac in acute headache management. Headache 1991;31:463-464 18. Buckley MM, Brogden RN: Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1990;39:86-109 19. Saper JR: Diagnosis and symptomatic treatment of migraine. Headache 1997;37suppl 1:S1-S14 20. Davis CP, Torre PR, Williams C, et al: Ketorolac versus meperidine-plus- promethazine treatment of migraine headache: evaluations by patients. Am J Emerg Med 1995;13:146-150 21. Harden RN, Gracely RH, Carter T, Warner G: The placebo effect in acute headache management: ketorolac, meperidine, and saline in the emrgency department. Headache 1996;36:352-356