5 HT receptor agonists (triptans) and Pediatric Migraine Critically Appraised Topic (CAT)

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1 5 HT receptor agonists (triptans) and Pediatric Migraine Critically Appraised Topic (CAT) PICOT Question: In children and adolescents does use of 5 HT receptor agonists (triptans) versus no treatment treat decrease migraine pain? Clinical bottom line based on literature appraisal below: The 5-HT receptor agonists ( triptans ) have been extensively studied in the treatment of pediatric migraine headache (Ahonen, Hämäläinen, Rantala, Hopp, 2004; Hämäläinen, Hoppu & Santavuori, 1997; Lewis, Hershey & Wasiewski, 2007; Rothner, Wasiewski, Winner, Lewis & Stankowski, 2006; Winner, Adelman, Aurora, Lener & Ames, 2006; Winner, Lewis, Visser, Jiang, Ahrens & Evans, 2002 Winner, Rothner, Wooten, Webster & Ames, 2006). Safety in the pediatric population has been well defined (Ahonen, Hämäläinen, Rantala, Hopp, 2004; Hämäläinen, Hoppu & Santavuori, 1997; Lewis, Hershey & Wasiewski, 2007; Rothner, Wasiewski, Winner, Lewis & Stankowski, 2006; Winner, Adelman, Aurora, Lener & Ames, 2006; Winner, Lewis, Visser, Jiang, Ahrens & Evans, 2002 Winner, Rothner, Wooten, Webster & Ames, 2006). Currently, the only triptan available at Children s Mercy Hospital is sumatriptan (Imitrex). The recommended dose and route of administration for the acute care setting is 0.06 mg/kg (maximum 6 mg) subcutaneously (SQ). Dosing of sumatriptan may be repeated for a total of two (2) doses in 24 hours two hours must elapse between repeat doses of triptans, including sumatriptan (Gunn & Nechyba, 2002). There should be no more than two triptan doses in a 24 hour period, and two different triptans should not be utilized in the same patient. Limitations to triptan use include the following: uncontrolled hypertension, chest pain, basilar migraine, or use of monoamine-oxidase inhibitors (MAOI s). Triptans should not be used concomitantly (or within 24 hours) with dihydroergotamine (DHE) (Gunn & Nechyba, 2002). [GRADE = Weak recommendation / Moderate-quality evidence] Search strategy implemented: (("Infusions, Intravenous"[Mesh] OR "Prochlorperazine"[Mesh] OR "Metoclopramide"[Mesh] OR "Ondansetron"[Mesh] OR "Promethazine"[Mesh] OR "Naproxen"[Mesh] OR "Ketorolac Tromethamine"[Mesh] OR "Diphenhydramine"[Mesh] OR "Valproic Acid"[Mesh] OR "Dihydroergotamine"[Mesh] OR "Methylprednisolone Hemisuccinate"[Mesh] OR "Magnesium"[Mesh] OR "Magnesium Sulfate"[Mesh] OR "Acetaminophen"[Mesh] OR "Ibuprofen"[Mesh] OR "Sumatriptan"[Mesh] OR "Adrenergic beta-antagonists"[mesh] OR "Antidepressive Agents, Tricyclic"[Mesh] OR "petadolex"[all Fields]) AND ("Migraine Disorders"[Mesh] OR "Headache"[Mesh] OR "Headache Disorders"[Mesh])) AND ("Adolescent"[Mesh] OR "Child"[Mesh] OR "Infant"[Mesh] OR "Child, Preschool"[Mesh] OR "pediatric"[all Fields] OR "paediatric"[all Fields]) AND ("humans"[mesh Terms] AND English[lang] AND (systematic[sb] OR Meta-Analysis[ptyp] OR Practice Guideline[ptyp] OR Randomized Controlled Trial[ptyp] NOT Case Reports[ptyp] OR Comparative Study[ptyp] OR Controlled Clinical Trial[ptyp])). Prochlorperazine articles were reviewed for this CAT. Search outcome: 15 papers were found and reviewed. Six studies treated children and adolescents. The remainder treated adults with migraine. The pediatric studies include one systematic review and 5 therapy studies. Synthesis of relevant studies: Author, date, country, and industry of Patient Group funding Lewis, D.,W., Adolescents Hershey, A.D., & years old for the Wasiewski, W.W. duration of the study (2007). On behalf of the adolescent HA were treated in migraine steering the moderate to committee. severe stage, Oxford / GRADE* Oxford: 1b Research design Significant results Limitations It was a multicenter, randomized, doubleblind, placebocontrolled, 2 way, 2 attack, crossover study, with a single blind placebo 171 subjects were treated, 148 with zolmitriptan and 127 with placebo 96 subjects completed sequence A 103 subjects completed sequence B At one hour: Higher HA response rate for the Subjects can taste the study drug, but this is common in all nasal triptan studies This report is not the intent to treat group, 1

2 Pediatrics 120, Mean age 14.2 y (+ 1.5) Rothner, A.D., Wasiewski,W., Winner, P., Lewis, D. & Stankowski, J.(2006). Zolmitriptan oral tablet in migraine Power was met Adolescents years were open to be in this study Mean age ITT population years (SD 1.7) Oxford 2b challenge for each migraine attack. zolmitriptan (5mg) nasal spray or placebo N= 248 who were randomized into each of two arms. Two migraine attacks were treated. Prior to receiving study drug, subjects were treated with placebo. If HA did not abate in 15 minutes, the study drug they were randomized to, was administered. Sequential randomization was used. 171 subjects were reported on. 80 in the placebo first, zolmitriptan second group 91 in the zolmitriptan first, placebo second group Randomized, doubleblind, placebocontrolled 10 mg, 5 mg or 2.5 mg of zolmitriptan zolmitriptan group (OR 1.827, 95% CI: P<0.05) Response in favor of zolmitriptan at 15 min (OR 2.020, 95% CI p< 0.05) 1.5 hours- NS 2 hours NS 2 hours sustained- (OR 2.243; 95% CI: p< 0.01) Pain free rates were higher with zolmitriptan at all times significant at 1 hour -27.7% vs 10.2% 1.5 hours % vs. 15.7% 2 hours % vs % All significant p<0.01 Early onset based on 1 point decrease in pain intensity 15 minutes-- 50% vs. 35.4%, p< minutes % vs %. p<0.05 Resolution of migraine symptoms at 30 minutes favored zolmitriptan Photophobia % vs. 19.6% p< 0.05 Phonophobia % vs. 21.4% p< 0.05 Return to normal activities favored zolmitriptan at all time points, significant at 45 minutes 48.0% vs. 33.9%, p< hour 55.1% vs. 41.3% p< 0.05 No difference in the worst case scenario (ITT analysis) Analysis was done in step wise fashion. If a significant result was found at the 10 mg. dose, the 5 mg dose was tested. If a significant result was found at the 5 mg dose, the 2.5 mg dose was tested. only those who finished both arms. No CIs Hawthorne effect Adult HA criteria Not enough points on the pain scale 2

3 treatments: High placebo responses in adolescents. Headache, 46, mg group N=179 5 mg groups, N= mg groups, N= 171 Placebo group, N= 175 tablet. Self treated moderate to severe migraine attacks There was no difference between treatment and placebo groups at One hour, 30 minutes. The placebo group had slightly better response rate at 2 hours. Winner, P., Rothner, D., Wooten, J., Webster, C. & Ames, M. (2006). Sumatriptan nasal spray in adolescent migraineurs: A randomized, double-blind, placebo-controlled, acute study. Headache, 46, Power was met The population studied was adolescents years of age Mean age 14 y (range y) 738 subjects were recruited, 245 in the placebo group, 255 in the sumatriptan 5 mg group and 238 in the sumatriptan 20 mg group. Power was met. Oxford: 2 b Randomized, placebo controlled, double-blind Randomized (1:1:1) in blocks of six. Self treated a single moderate to severe migraine attack. Sumatriptan NS at 5, and 20 mg vs. placebo Primary outcomes: no significant difference was found between HA relief rates at one hour (61% vs. 52%). Sustained relief rates from 1 to 24 hours post dose were not significant. The proportion of subjects reporting pain free was significantly higher in the sumatriptan NS 20 mg group at 2 hours post dose (44% vs. 30%) p < 0.001, however not at one hour. Secondary outcomes HA relief at time points through 2 hours with sumatriptan NS 20 mg than with placebo within 2 hours post dose (76% vs.65% p = 0.007). The probability of achieving pain free results was significantly greater with sumatriptan NS 20 mg (cumulative percentages of subjects: 45% vs. 34% respectively p = 0.014). Pain free rate was significantly higher in the sumatriptan NS 20 mg group at 2 hours post does (41%vs. 28%, p = 0.003). Photophobia was significantly lower in the sumatriptan NS 20 mg group at 2 hours postdose (31% vs. 36% p = 0.019). Photophobia plus phonophobia was lower in the sumatriptan NS 20 mg (21% vs 29% p = 0.044). Use of rescue medication- was not significantly different. HA recurrence( return of moderate or severe pain 1-24 hours after HA relief at one hour) was not significantly CIs are not reported The data on the secondary endpoints suggest benefit, not primary end points. Again high Hawthorne effect plays a role. 3

4 Ahonen, K., Hämäläinen, M.L,, Rantala H., & Hoppu K. (2004). Nasal sumatriptan is effective in treatment of migraine attacks in children: A randomized trial. Neurology, 62, Winner, P., Lewis, D.L., Visser, H., Jiang, K., Ahrens, S., & Evans, J.K. (2002), Rizatriptan 5 mg for the acute treatment of migraine in adolescents: A randomized, doubleblind, placebocontrolled study. Children and adolescents between 8 and 17 years of age N= 83 used both treatments N= 94 used at least one treatment (ITT) Mean age of children studied was 14 years (range, years) Power was met Adolescents between 12 and 17 y with an average of at least 1 but < 8 migraine headaches (based on the International Headache Society criteria) per month over the previous six months whose migraines lasted on average at least 4 Oxford : 2b Oxford: 2b Double blind, randomized, placebo-controlled, two-way crossover design Two moderate to severe migraine attacks were treated at home with study drugs. 10 mg for body weight kg and 20 mg of body weight > 40 kg A five point HA scale was used 5 severe, 4 to 3 moderate, 2 mild, 1 no pain Randomized, double-blind, placebo-controlled study. Treatment Rizatriptan 5 mg vs placebo different. Tolerability evaluation. AE reporting major AE was taste disturbance. No serious AE was reported. Data is reported as a proportion of subjects experiencing an outcome. p values are reported, CIs are not. ITT 94 subjects 177 treatments (90 treatment 87 placebo) Primary end point (HA relief at least 2 points lower in 2 hours time) was improved in the sumatriptan group. 67% vs. 38% p< Secondary endpoints (at 30 minutes post treatment relief from sumatriptan) was slightly superior to placebo 31% Vs 16% p = 0.03 at one hour post treatment relief was better in the sumatriptan than the placebo 53% vs 29% p =0.003 no significance was found between treatment and placebo and total pain free response at 1 hour, or 2 hours post treatment. Rescue meds were taken more after treatment with placebo than sumatriptan 51% vs 32 p = 0.03 AE occurred in 44% of patients, 39% after sumatriptan and 8% after placebo. No serious AE. Most common was bad taste. AE s placebo patients has a significantly higher incidence of nausea and somnolence then treatment group. Pain-free and Pain-relief: Difference was not significant between tx and placebo group. Associated symptoms at baseline: More placebo pts reported nausea than the tx group. Nausea was significantly higher in the placebo group at 1, 1.5, and 4 hours. This reporting might be related to the higher numbers of pts. No CIs The report of taste difference was considered to have unblinded in some instances. Therefore secondary analysis of the first period was done, which had stronger results. It is reported here: Treatment with sumatriptan was 50% effective vs. 21% placebo (p=0.004) at one hour Treatment with sumatriptan was 74% in the treatment group vs. 33% in the placebo group. [< 0.001) Taste of the study drug distinguished the treatment- unblinded the study to the subject. All groups were fairly balanced with the exception of the baseline headache severity groups. The treatment group participants identified 63% with a moderate baseline headache and 37% having a severe headache compared to the placebo group 4

5 Headache, 42, Hämäläinen, M.L., Hoppu, K., & Santavuori P. (1997). Sumatriptan for migraine attacks in children: A randomized placebo controlled study. Neurology, 48, Winner, P., Adelman, J., Aurora, S., Lener, M.E. & Ames, M. (2006). Efficacy and tolerability of sumatriptan injection for the treatment of morning migraine: Two multicenter, prospective, randomized, doubleblind, controlled studies in adults. hours. Treatment group n=149 Placebo group n=147 Mean age 14 Power was met Children > 8 years old.mean age12.3 years (range, ) years old N= 23 children Power calc not done yoa with a > 1 yr hx of migraine with or without aura as defined by the International Headache Society; experience 1-6 migraines/month during each of the 3 previous months, had awakened with moderate to severe migraine pain at Oxford: 2 b Oxford:1 b Double blind randomized placebo controlled two way crossover sumatriptan 50 mg for a body surface area of 0.75 to 1.5 m 2, and 100 mg of a body surface > 1.5 m 2 Randomized, double-blind, parallel-group studies Dose: Sumatriptan injection 6 mg or matching inactive placebo; pts self administered medication within an hour of waking with a moderate severe migraine; reporting nausea in the placebo group at baseline. Functional disability: At 1.5 and 2 hours the tx group reported a significant (p =.03 and.03 respectively) ability to function normally Additional medication required was not significant. Recurrence 11% of tx group and 18% of placebo group had a recurrence; no analysis was performed. They showed no difference in pain resolution if the subjects took sumatriptan or placebo, as measured by 50% pain resolution at 2 hours after treatment. 7/23 showed 50% pain reduction after drug and 5/23 show pain reduction after placebo. 95% CI for the difference -21 to38% p = ns. HA resolution. 5/23 had complete resolution of pain after drug and 2/23 had resolution after placebo. 95% confidence interval for the difference -9 to35 p =ns. Reduction in pain intensity. Pain intensity difference was not different. Neither treatment order nor period had significant effects on pain intensity difference (start to 2 hours after treatment) and sum of pain intensity difference. Tx grps proved to be more effective 48% & 57% vs. control gps 18% & 19% (p <.001); with the onset of pain-free response 30 minutes and 20 minutes in the tx groups ( p<.01). Tx groups headache relief after 2 hours 72% and 77% vs control grps 41% & 32% (p <.001); Efficacy of tx occurred by 20 minutes after tx and 10 minutes after tx in the tx grps (p <.01). Migraine associated symptoms were significantly lower in tx grps than in control grps at 2 hours (p <.001). which had 53% with a moderate baseline headache and 44% with a severe headache. Did not truly randomize; the subjects self randomize. Didn t define the terms escape and rescue meds. Unknown pharmacokinetics for sumatriptan in children. Only used the tablet form. Did not report on lost subjects. IM medication is selfadministered. Multiple exclusion criteria (uncontrolled hypertension, cardiovascular or cerebrovascular disease, basilar or hemiplegic migraine, current use of migraine controlling medication containing ergotamine, ergot derivative, or 5

6 Clinical Therapeutics, 28, Scholpp, J., Schellenberg, R., Moeckesch, B. & Banik, N. (2004). Early treatment of a migraine attack while pain is still mild increased the efficacy of sumatriptan. Cephalagia, 24, Supported by GlaxoSmithKline. Kelly, A.M., Ardagh, M., Curry, C., D Antonio, J., & Zebic, S. (1997). Intervenous chlorpromazine versus intramuscular sumatriptan for acute migraine. J Accident and Emergency Medicine,14, least once in the 3 previous months. Study 1 N=297, Tx grp, n=145, Control, n=152; Study 2, N=287, Tx grp, n=148, Control, n=139. Adults Early ( first sign of pain and not later than one hours after onset of pain) or late (wait until pain was at least moderate or severe (at least grade 2 or 3) treatment with 100 mg tablet of sumatriptan Adults with migraine subjects (mean age) 35 years Control 32 years Oxford: 1B Oxford: 1b pts could administer a second dose or use a rescue medication 2 hours after the initial dose if they experienced inadequate pain relief Prospective controlled and open label study Randomized Sumatriptan 100 mg oral early Control Sumatriptan 100 mg oral late Prospective, randomized unblinded crossover trial chlorpromazine mg IV Control: sumatriptan 6 mg IM Pain-free response sustained in 32% & 34% of patients in tx group than in control grps 14% & 15% (p <.001). Normal function before tx 0%-1% in tx grps.; 2 hrs after intervention tx grp reported 49% & 61%, control grp 22% & 21% (p <.001). Tx grp pts used a lower percentage of second dose or rescue meds within 24 hour time period (46% & 46%) vs. control grp (63% & 65%). Primary outcome- the percentage of patients who were completely pain free at 2 hours after taking study medication was significantly greater (p = 0.43) in the early intervention group, (n = 59/89, 71.1%, 95% CI %) when compared to the late intervention group (n = 38/70, 54.3%, 95% CI %). No difference between mg of chlorpromazine IV versus 6 mg of sumatriptan IM. methysergide and use of monoamine oxidase inhibitor) which may limit generalization to entire population. Study was done by the company who makes the drug. In the early treatment group AEs were reported as drug effect, where they may have been migraine effect, whereas the late group may have had the same AEs and attributed them to the HA. Open label, so the subjects knew they were getting drug- Hawthorne Effect may have increased reported efficacy. Randomization was not clear. The major difference was the IV that had to be inserted to administer the chlorpromazine. Although both groups received 1L of fluid, it appears the chlorpromazine group received more fluid, although it is not accounted for in the results. A power calculation was 6

7 not done. Boureau, F., Chazot, G., Emile, J., Bertin, L., & d Allens, H. (1995). Comparison of subcutaneous sumatriptan with usual acute treatments for migraine. European Neurology 35, Major, P.W., Grubisa, H.S.I. & Thie, N.M.R. (2003). Triptans for treatment of acute pediatric migraine: a systematic literature review. Pediatric Neurology, 29, Lampl, C., Huber, G., Haas, S., Ritteberger, E. & Diener, H.C. (2008). Difference in triptan effect in patients with migraine and early allodynia. Adults y Mean age 42 (range 20-65) N= 217 evaluable patients treating a total of 3181 attacks. Treatment groups were similar Studies who included children 6-18 years old with migraine not responsive to other interventions Four studies were found for effectiveness and four studies were found for safety Adults years N= 36 Six subjects per group (mean age): Zolmitriptan 1.5 mg (37.6 ) Eletriptan 80 mg (33.3) Oxford: Oxford- 2b Oxford: 1a- Oxford:2 B low quality RCT Randomized, crossover Control: usual migraine treatment Intervention: Subcutaneous sumatriptan 6 mg auto-inject device versus Only randomized, placebo controlled, double blinded studies were included to study effectiveness Studies published in English and French were searched. Does not state which bibliographic databases were used, if personal contact was made with experts, if unpublished data was used, Reports were chosen by abstract. Discussion by the three authors was how decisions were made. Studies were not blinded. Randomized 6 subjects in each of 6 groups Treatment of 3 consecutive HA with Zolmitriptan 1.5 mg The treatment group had significantly Shorter duration of HA (p < 0.001) Less use of rescue drugs not different Less nausea p < Higher patient rating (p < 0.001) Improvement in quality of life score (p < for global, psychological and social, p = for functional. Iatrogenic disturbance was not significant. Only nasal sumatriptan was better for children and adolescents with migraine VAS score was significantly improved for subject on zolmitriptan nasal spray 5 mg (p = 0.0.5) versus 5 other triptans VAS score was reduced to < 3 in one hour for zolmitriptan nasal spray (regression coefficient G, 2.30: standard error, 0.99; Wald, 5.36; d.f =1; p = 0.21 Exp B = 10; 95% Not blinded Study drug compared to many different migraine drugs Wash out period not discussed Statistics could be stronger Could not combine results, since different drugs were used in each study No p values given Randomization is poor Power calculation was not performed They talk about time after onset of HA that medicines are taken, however there is no mention in the study 7

8 Cephalagia,2, Tfelt-Hansen, P., Bach, F.W., Daugaard, D., Tsiropoulos, I., & Riddersholm, B. (2006). Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in patients with infrequent attacks: A randomized doubleblind, placebocontrolled study. Journal of Headache Pain, 7, Dodick, D., Brandes, J., Elkind, A., Mathew, N. & Rodichok, L (2005). Speed of onset, efficacy and tolerability of zolmitriptan nasal spray in the acute treatment of migraine. CNS Drugs 19, 2, Naratriptan 2.5 mg (36.6) Frovatriptan 2.5 mg (33.3) Zolmitriptan nasal spray 5 mg (32.8) Eletriptan 40 mg (31.2) Adults N= receiving placebo; Mean age receiving treatment; Mean age=38 Adults aged N=2122 screened 935 in zolmitriptan group Age distribution > years 43.7% and >40-69 years 44.4 % placebo group n= 933 age distribution years 44.4% and % Oxford: 1b Oxford:1 b Eletriptan 80 mg Naratriptan 2.5 mg Frovatriptan 2.5 mg Zolmitriptan nasal spray 5 mg Eletriptan 40 mg Control: each other Double blind, placebo controlled, parallel group and randomized 50 mg sumatriptan Control: Placebo Multi-center randomized,doubl e blind parallel group Zolmtriptan5 mg nasal spray Control: placebo to treat up to two migraine attacks within 15 minutes of HA pain becoming moderate/severe confidence interval exp G ) 38% of patients in the intent to treat population were pain free after 2 hours. (95 CI: 25%-53%) Results are presented as percentage of subjects with pain relief using a VAS. Zolmitriptan nasal spray produced a signifiacant p < HA response at 2 hours compared with placebo (66.2% vs. 35.0%), (p < 0.001). All prior time points were significantly better in the zolmitriptan group than the placebo group. Secondary outcomes- Zolmitriptan had significantly higher pain free assessment from the earliest assessment (15 minutes) onward (p < ). design giving the directions relating to time after onset of symptoms that the study med should be taken. Confidence intervals were not used on the primary outcomes. No report if the 12 who dropped out just prior to randomization were different than those who stuck with the study. 33% subjects waited until the severity of pain was at least moderate before treatment. Did not exactly follow protocol. Missing values from the HA diaries were problematic; subjects were not used to filling out HA diaries and follow the protocol. Taste of the zolmitriptan potentially un blinded the treatment subjects. 8

9 Burstein, R., Collins, B. & Jakubowski, M. (2004). Defeating migraine pain with triptans: A race against the development of cutaneous allodynia. Annals of Neurology,55, Adults age years old Mean age 36.2 range, patients were evaluated and 31 patients participated. Oxford- 2b cohort study 24 hour wash out period. Cohort study patients who failed to reach a pain free state after late sumatriptan treatment were asked for a fourth visit 4 hours into another attack.. They were treated with rizatriptan 10 mg or melting zolmtriptan 5 mg tablet Time to onset of HA response was greater in the zolmitriptan group (p < ). Zolmtriptan group used less rescue medication (p < 0.001) and less remedication (0.0001) than the placebo group. Significance was achieved for the resolution of nausea and phonophobia from 15 minutes onward and photophobia 30 minutes onward. Global impressions- subjects preferred the zolmitriptan significantly greater than placebo (p < 0.001). Recurrence and time to recurrence were greater in the zolmitriptan group, but not significantly. Subjects were prepared to use zolmitriptan nasal spray as treatment for HA after this trial. AEs were similar in both groups. The results are presented as presence or absence of allodynia and VAS scores for early and late treatment of HA. Patients without allodynia were more likely to be pain free than patients with allodynia. Early triptan treatment successfully yielded a pain free state in 15 of 17 nonallodynic attacks and only 1 of 12 in allodynic attacks (p < 0.001). Late triptan treatment successfully yielded a pain free state in 10 of 10 nonallodynic attacks and 4 of 22 allodynic attacks (p <0.001). In allodynic attacks, triptans decreased throbbing, but did not significantly decrease allodynia. The prospect of achieving complete pain relief with triptans was strongly associated with the absence of allodynia. Within 2 hours of treatment the painfree state was achieved in 93% of attacks without allodynia and only 15% Patients knew they were getting drug potential Hawthorne Effect 9

10 Meredith, J.T., Wait S. & Brewer, K.L. (2003). A prospective double blind study of nasal sumatriptan versus IV ketorolac in migraine. American Journal of Emergency Medicine, 21, Adults received (mean age 33 years (range, 18-54)) IV ketorolac 16 received (mean age349range,19-56)) nasal sumatriptan Convenience sample Oxford:2b RCT no CIs given Prospective double blind randomized comparison study Sumatriptan nasal spray 20 mg or Control: Ketorolac 30 mg IV of attacks with allodynia. Sumatriptan significantly decreased migraine pain one hour after treatment. p < Reduction in VAS from mm before treatment to mm after treatment, power = 80-90% at p < Ketorolac significantly decreased migraine pain one hour after treatment from mm to mm after ketorolac. Both were significant at p < Pain reduction was greater in patients who received IV ketorolac than in those receiving nasal sumatriptan p < 0.05, 95% power at p < Convenience sample No follow up for recurrence of HA, medication side effects outside the ED, only one hour follow up, other studies have had 2 hour follow up. Literature synthesized by: Nancy H Allen MS RD LD CNSC J. Bartlett, RN, MSN, MBA/HCM Clinical Bottom Line developed by Migraine CPG team. Date created: 5/09 References: Ahonen, K., Hämäläinen, M.L,, Rantala H., & Hoppu K. (2004). Nasal sumatriptan is effective in treatment of migraine attacks in children: A randomized trial. Neurology, 62, Burstein, R., Collins, B. & Jakubowski, M. (2004). Defeating migraine pain with triptans: A race against the development of cutaneous allodynia. Annals of Neurology,55, Boureau, F., Chazot, G., Emile, J., Bertin, L., & d Allens, H. (1995). Comparison of subcutaneous sumatriptan with usual acute treatments for migraine. European Neurology 35, Dodick, D., Brandes, J., Elkind, A., Mathew, N. & Rodichok, L (2005). Speed of onset, efficacy and tolerability of zolmitriptan nasal spray in the acute treatment of migraine. CNS Drugs 19, 2, Gunn, V.L, & Nechyba, C. (2002). The Harriet Lane handbook (16 th ed). St. Louis, MO: Mosby. Hämäläinen, M.L., Hoppu, K., & Santavuori P. (1997). Sumatriptan for migraine attacks in children: A randomized placebo controlled study. Neurology, 48, Kelly, A.M., Ardagh, M., Curry, C., D Antonio, J., & Zebic, S. (1997). Intervenous chlorpromazine versus intramuscular sumatriptan for acute migraine. J Accident and Emergency Medicine,14, Lampl, C., Huber, G., Haas, S., Ritteberger, E. & Diener, H.C. (2008). Difference in triptan effect in patients with migraine and early allodynia. Cephalagia,2, Lewis, D.,W., Hershey, A.D., & Wasiewski, W.W. (2007). On behalf of the adolescent migraine steering committee. Pediatrics 120, Major, P.W., Grubisa, H.S.I. & Thie, N.M.R. (2003). Triptans for treatment of acute pediatric migraine: a systematic literature review. Pediatric Neurology, 29,

11 Meredith, J.T., Wait S. & Brewer, K.L. (2003). A prospective double blind study of nasal sumatriptan versus IV ketorolac in migraine. American Journal of Emergency Medicine, 21, Rothner, A.D., Wasiewski,W., Winner, P., Lewis, D. & Stankowski, J.(2006). Zolmitriptan oral tablet in migraine treatments: High placebo responses in adolescents. Headache, 46, Scholpp, J., Schellenberg, R., Moeckesch, B. & Banik, N. (2004). Early treatment of a migraine attack while pain is still mild increased the efficacy of sumatriptan. Cephalagia, 24, Supported by GlaxoSmithKline. Tfelt-Hansen, P., Bach, F.W., Daugaard, D., Tsiropoulos, I., & Riddersholm, B. (2006). Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in patients with infrequent attacks: A randomized double-blind, placebo-controlled study. Journal of Headache Pain, 7, Winner, P., Adelman, J., Aurora, S., Lener, M.E. & Ames, M. (2006). Efficacy and tolerability of sumatriptan injection for the treatment of morning migraine: Two multicenter, prospective, randomized, double-blind, controlled studies in adults. Clinical Therapeutics, 28, Winner, P., Lewis, D.L., Visser, H., Jiang, K., Ahrens, S., & Evans, J.K. (2002), Rizatriptan 5 mg for the acute treatment of migraine in adolescents: A randomized, double-blind, placebo-controlled study. Headache, 42, Winner, P., Rothner, D., Wooten, J., Webster, C. & Ames, M. (2006). Sumatriptan nasal spray in adolescent migraineurs: A randomized, double-blind, placebo-controlled, acute study. Headache, 46,