1. Metoclopramide versus Hydromorphone for the ED Treatment of Migraine Headaches Justin Griffith, MD Mark Mycyk, MD Demetrios Kyriacou, MD, PhD ICEP Resident Research Forum NMH Division of Emergency Medicine April 29, 2004

2. Lipton R: Headache 2001 Background 28 million Americans with migraines 15% of migraineurs seek ED evaluation $5-17 billion in lost economic productivity

3. Background Exact etiology of migraines remains unclear Complex phenomenon of select neurotransmitter interactions and cerebral vascular flow Opioid receptor not implicated in primary pathophysiology of migraines

4. Vinson D: Ann Emerg Med 2003 Background Multiple pharmaceutical options Prochlorperazine (Compazine ® ) and Droperidol (Inapsine ® ) previously identified as the most effective ED abortive migraine agents – availability now limited

5. Vinson D: Ann Emerg Med 2003 Background Acetaminophen Dexamethasone Dihydroergotamine Diphenhydramine Fentanyl Hydromorphone Ketorolac Lidocaine Magnesium Meperidine Metoclopramide Morphine Naproxen Ondansetron Promethazine Prednisone Sumatriptan Tramadol Valproate Zolmitriptan

6. Ellis D: Ann Emerg 1993 Vinson D: Ann Emerg Med 2003 Background (NMH) Metoclopramide(Reglan ® ) Dopamine and serotonin receptor activity Previous studies support its effect on migraines Hydromorphone(Dilaudid ® ) Opioid receptor activity Opioids are used more commonly than non-opioids for ED treatment of migraines

7. Study Objective To evaluate the effectiveness of intravenous metoclopramide vs. hydromorphone as the initial abortive treatment of migraines in the Emergency Department.

8. Methods Retrospective cohort study of patients with migraine headaches treated in NMH ED NMH ED: Urban, academic, 75,000/year Complete ED chart review

9. Methods Inclusion Criteria: – All ED patients with a discharge diagnosis of Migraine from October 2002 to March 2003 Exclusion Criteria: – Non-migraine co-morbidities – Incomplete charts – Patients whose discharge diagnosis of migraine not consistent with patient’s ED evaluation – Migraine patients who received no intervention

10. Todd K: Ann Emerg Med 1996 Methods A validated, nursing administered numerical pain scale (0-10) was used to assess effectiveness of treatment interventions. Chi-squared analyses were performed to assess pain score changes. Cox proportion hazards multivariate regression analyses were performed to adjust for confounders.

11. Results Study Population: 183 subjects Ages 18-79 years (mean 40) 85.8% female

12. Results Number of Subjects Metoclopramide: 89 Hydromorphone:48 All Other Medications46 There were no significant age, gender, race, or initial pain score differences among the three groups

13. Results Mean Pain Score Reductions Metoclopramide: - 3.85 Hydromorphone: - 2.15 All others combined: - 2.61 (ANOVA F statistic 7.42, P-value: 0.0009)

14. Results Metoclopramide vs. Hydromorphone For an effective pain reduction of 3 or more: Crude RR: 1.70 (95% CI, 1.15-2.53) P value: 0.003 Adjusted RR: 1.87 (95% CI, 0.95-3.69) P value: 0.072

15. Results Metoclopramide Effective Pain Reduction P value = 0.165 206 2818 20/26 = 0.77 10 mg 20 mg YesNo 206 2818 28/46 = 0.61

16. Results 4/14 = 0.29 Hydromorphone 0.5 mg 2.0 mg Effective Pain Reduction YesNo 410 0 5 P value = 0.241 1.0 mg 4.0 mg 1113 12 11/24 = 0.46 0/5 = 0 1/3 = 0.33

17. Conclusion Metoclopramide appears to be more effective than hydromorphone as an initial ED treatment of migraine headaches. Increasing doses of metoclopramide and hydromorphone demonstrated no significant pain reduction.

18. Limitations Retrospective analysis Dosing and timing of interventions could not be controlled Unequal numbers in each treatment group

19. Future Endeavors Prospective randomized trial Varied dosing regimens Sub-group analysis

20. References Cameron JD, Lane PL, et al. Intravenous chlorpromazine vs. intravenous metoclopramide in acute migraine headache. Acad Emerg Med 1995; 2:597- 602. Coppola M, Yealy DM, et al. Randomized, placebo-controlled evaluation of prochlorperazine vs. metoclopramide for ED treatment of migraine headache. Ann Emerg Med 1995. 26:529-30. Ellis GL, Delaney J, et al. The efficacy of metoclopramide in the treatment of migraine headache. Ann Emerg Med 1993; 22:191-5. Gralla R, Itri L, et al. Antiemetic efficacy of high-dose metoclopramide. New England Journal of Medicine. Oct 1981; 305:905-9. Miner J, Fish S., et al. Droperidol vs. Prochlorperazine for benign headaches in the ED. Acad Emerg Med 2001; 8:873-9. Tek DS, McClellan DS, et al. A prospective, double-blind study of metoclopramide for the control of migraine in the ED. Ann of Emerg Med 1990; 19:1083-7. Todd KH, Funk KG et al. Clinical significance of reported changes in pain severity. Ann of Emerg Med 1996;27:485-9. Vinson DR, Hurtado TR, et al. Variations among EDs in the treatment of benign headache. Ann Emerg Med 2003; 41:190-97.

21. With Gratitude Mark Mycyk, MD Demetrios Kyriacou, MD, PHD NMH ICEP