Metoclopramide and Diphenhydramine: A Randomized Controlled Trial of a Treatment for Headache in Pregnancy when Acetaminophen Alone Is Ineffective (MAD Headache Study)

Katherine M. Scolari Childress; Christina Dothager; Jeffrey A. Gavard; Sara Lebovitz; Catherine Laska; Dorothea J. Mostello

doi:10.1055/s-0038-1646952

American Journal of Perinatology, Table of Contents

Am J Perinatol 2018; 35(13): 1281-1286
DOI: 10.1055/s-0038-1646952

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Metoclopramide and Diphenhydramine: A Randomized Controlled Trial of a Treatment for Headache in Pregnancy when Acetaminophen Alone Is Ineffective (MAD Headache Study)

Katherine M. Scolari Childress

¹Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Women's Health, Saint Louis University School of Medicine, St. Louis, Missouri

,

Christina Dothager

¹Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Women's Health, Saint Louis University School of Medicine, St. Louis, Missouri

,

Jeffrey A. Gavard

¹Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Women's Health, Saint Louis University School of Medicine, St. Louis, Missouri

,

Sara Lebovitz

¹Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Women's Health, Saint Louis University School of Medicine, St. Louis, Missouri

,

Catherine Laska

¹Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Women's Health, Saint Louis University School of Medicine, St. Louis, Missouri

,

Dorothea J. Mostello

¹Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Women's Health, Saint Louis University School of Medicine, St. Louis, Missouri

› Author Affiliations

Abstract

Objective We investigated whether metoclopramide administered with diphenhydramine (MAD) relieves headache in pregnant women when acetaminophen alone is ineffective, using codeine for comparison.

Study Design Normotensive pregnant women in the second or third trimester were randomized to MAD intravenously (10 mg and 25 mg, respectively) or codeine orally (30 mg) for headache after 650 to 1,000 mg of acetaminophen failed to relieve their headaches. Headache severity (pain score 0–10) was noted at intervals over 24 hours. The primary outcome was reduction in pain score 6 hours after medication administration. A sample size calculation of 35 patients per group was based on estimated reduction in headache pain score by at least two points, with an α of 0.05 and a power of 80%.

Results No difference was seen in the primary outcome. MAD pain scores were lower at 30 minutes (3 ± 2.8 versus 5.8 ± 2.3, p < 0.001), 1 hour (2.2 ± 2.3 vs. 4.1 ± 3; p < 0.01), and 12 hours (1.3 ± 2.5 vs. 2.7 ± 3; p < 0.05), but not at 6 hours. Time to perceived headache relief was shorter for MAD than for codeine (20.2 ± 13.4 vs. 62.4 ± 62.2 minutes; p < 0.001). More patients in the MAD group reported full headache relief within 24 hours (76.5 vs. 37.5%; p < 0.01).

Conclusion MAD effectively relieves headaches in pregnant women when acetaminophen fails.

Keywords

headache - pregnancy - metoclopramide - diphenhydramine - codeine

Full Text

References

References
1 Digre KB. Headaches during pregnancy. Clin Obstet Gynecol 2013; 56 (02) 317-329
2 Pearce CF, Hansen WF. Headache and neurological disease in pregnancy. Clin Obstet Gynecol 2012; 55 (03) 810-828
3 Macgregor EA. Headache in pregnancy. Continuum (Minneap Minn) 2014; 20 (1 Neurology of Pregnancy): 128-147
4 MacGregor EA. Migraine in pregnancy and lactation. Neurol Sci 2014; 35 (Suppl. 01) 61-64
5 Williams SH, Kehr HA. An update in the treatment of neurologic disorders during pregnancy--focus on migraines and seizures. J Pharm Pract 2012; 25 (03) 341-351
6 Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 55 (06) 754-762
7 Evers S, Afra J, Frese A. , et al; European Federation of Neurological Societies. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol 2009; 16 (09) 968-981
8 Bendtsen L, Evers S, Linde M, Mitsikostas DD, Sandrini G, Schoenen J. ; EFNS. EFNS guideline on the treatment of tension-type headache - report of an EFNS task force. Eur J Neurol 2010; 17 (11) 1318-1325
9 Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache 2015; 55 (01) 3-20
10 Gilmore B, Michael M. Treatment of acute migraine headache. Am Fam Physician 2011; 83 (03) 271-280
11 Callan JE, Kostic MA, Bachrach EA, Rieg TS. Prochlorperazine vs. promethazine for headache treatment in the emergency department: a randomized controlled trial. J Emerg Med 2008; 35 (03) 247-253
12 Cameron JD, Lane PL, Speechley M. Intravenous chlorpromazine vs intravenous metoclopramide in acute migraine headache. Acad Emerg Med 1995; 2 (07) 597-602
13 Bachur RG, Monuteaux MC, Neuman MI. A comparison of acute treatment regimens for migraine in the emergency department. Pediatrics 2015; 135 (02) 232-238
14 Ellis GL, Delaney J, DeHart DA, Owens A. The efficacy of metoclopramide in the treatment of migraine headache. Ann Emerg Med 1993; 22 (02) 191-195
15 Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials. BMJ 2004; 329 (7479): 1369-1373
16 Salazar G, Fragoso M, Vergez L, Sergio P, Cuello D. Metoclopramide as an analgesic in severe migraine attacks: an open, single-blind, parallel control study. Recent Patents CNS Drug Discov 2011; 6 (02) 141-145
17 Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med 2009; 360 (24) 2528-2535
18 Headache Classification Committee of the International Headache S. The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2013;33: 629-808
19 Todd KH, Funk JP. The minimum clinically important difference in physician-assigned visual analog pain scores. Acad Emerg Med 1996; 3 (02) 142-146
20 Kwong WJ, Pathak DS. Validation of the eleven-point pain scale in the measurement of migraine headache pain. Cephalalgia 2007; 27 (04) 336-342
21 Kelly AM. Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain?. Acad Emerg Med 1998; 5 (11) 1086-1090
22 Friedman BW, Corbo J, Lipton RB. , et al. A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines. Neurology 2005; 64 (03) 463-468
23 Friedman BW, Esses D, Solorzano C. , et al. A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. Ann Emerg Med 2008; 52 (04) 399-406
24 Talabi S, Masoumi B, Azizkhani R, Esmailian M. Metoclopramide versus sumatriptan for treatment of migraine headache: a randomized clinical trial. J Res Med Sci 2013; 18 (08) 695-698
25 Griffith JD, Mycyk MB, Kyriacou DN. Metoclopramide versus hydromorphone for the emergency department treatment of migraine headache. J Pain 2008; 9 (01) 88-94
26 Friedman BW, Adewunmi V, Campbell C. , et al. A randomized trial of intravenous ketorolac versus intravenous metoclopramide plus diphenhydramine for tension-type and all nonmigraine, noncluster recurrent headaches. Ann Emerg Med 2013; 62 (04) 311-318
27 Agosti RM. 5HT1F- and 5HT7-receptor agonists for the treatment of migraines. CNS Neurol Disord Drug Targets 2007; 6 (04) 235-237
28 Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 3: opioids, NSAIDs, steroids, and post-discharge medications. Headache 2012; 52 (03) 467-482
29 Colman I, Rothney A, Wright SC, Zilkalns B, Rowe BH. Use of narcotic analgesics in the emergency department treatment of migraine headache. Neurology 2004; 62 (10) 1695-1700
30 Friedman BW, Mulvey L, Esses D. , et al. Metoclopramide for acute migraine: a dose-finding randomized clinical trial. Ann Emerg Med 2011; 57 (05) 475-482