FPIN’s Clinical Inquiries

Treatment of Motion Sickness MATTHEW SUTTON, MD, and ANNE L. MOUNSEY, MD, University of North Carolina School of Medicine, Chapel Hill, North Carolina ROGER G. RUSSELL, MLS, East Carolina University, Greenville, North Carolina

Clinical Inquiries provides Clinical Question FIRST-GENERATION ANTIHISTAMINES answers to questions submitted by practicing What is the best medication for the treatment Numerous histamine H1 receptor antagonists family physicians to the of motion sickness? are available over the counter and by pre- Family Physicians Inquiries scription, including dimenhydrinate, chlor- Network (FPIN). Members Evidence-Based Answer of the network select pheniramine, diphenhydramine (Benadryl), questions based on their Scopolamine should be used to reduce nau- and meclizine. One small RCT (n = 16) relevance to family medi- sea associated with motion sickness, but it found that dimenhydrinate reduced nausea cine. Answers are drawn does not reduce vomiting. (Strength of Rec- scores more than placebo, and another found from an approved set of evidence-based resources ommendation [SOR]: A, based on multiple that high-dose (12-mg) chlorpheniramine and undergo peer review. randomized controlled trials [RCTs].) First- reduced the risk of severe malaise more than The strength of recom- generation antihistamines (dimenhydrinate placebo2,3 (Table 11-10). A higher incidence mendations and the level and chlorpheniramine) can also be used to of dry mouth was found with dimenhydri- of evidence for individual studies are rated using reduce nausea associated with motion sick- nate, and more sedation was reported with criteria developed by the ness. (SOR: B, based on multiple RCTs.) chlorpheniramine. Evidence-Based Medicine Scopolamine is more effective than mecli- Working Group (http:// zine (Antivert) and as effective as dimen- SECOND-GENERATION ANTIHISTAMINES www.cebm.net/?o=1025). hydrinate. Ondansetron (Zofran) and the One RCT with 18 healthy participants eval- The complete database second-generation antihistamines cetirizine uated the second-generation, nonsedating of evidence-based ques- tions and answers is (Zyrtec) and fexofenadine (Allegra) do not antihistamines cetirizine and fexofenadine in copyrighted by FPIN. If reduce symptoms of motion sickness and lab-induced motion sickness, and found no interested in submit- should not be used. (SOR: B, based on statistically significant difference in motion ting questions or writing small RCTs.) Ginger can be used to reduce sickness scores compared with placebo.4 answers for this series, go to http://www.fpin. symptoms of motion sickness. (SOR: B, ONDANSETRON org or email: questions@ based on RCTs with conflicting results.) fpin.org. Two well-designed RCTs that included a total A collection of FPIN’s Evidence Summary of 86 participants with sea- or lab-induced Clinical Inquiries pub- SCOPOLAMINE motion sickness found that ondansetron did lished in AFP is available A Cochrane review of 14 RCTs with a total of not reduce motion sickness symptoms com- at http://www.aafp.org/ 5,6 afp/fpin. 1,025 participants who had sea- or lab-induced pared with placebo. motion sickness compared scopolamine with placebo and various other agents.1 Scopol- GINGER amine reduced nausea more than placebo Two higher-quality, placebo-controlled (relative risk reduction = 0.47; 95% confi- RCTs found that ginger reduced vomiting dence interval, 0.31 to 0.71) but did not reduce (but not nausea) in the larger trial, and vomiting. Patients receiving scopolamine delayed the onset and reduced the inten- were more likely to have dry mouth (a 22 to sity of nausea in the smaller trial.7,8 Two 50 percent increase). Three of the RCTs com- older RCTs comparing ginger with placebo pared scopolamine with antihistamines. Two for lab-induced motion sickness produced studies found scopolamine to be superior to conflicting results; one found that ginger meclizine, and one found it to be equivalent delayed the onset of nausea, whereas the other to dimenhydrinate.1 found no difference in severe malaise.9,10 ▲

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Table 1. Randomized Controlled Trials of Motion Sickness Medications vs. Placebo

Number of Motion Outcome Medication participants stimulus measured Results

Scopolamine (various 1,025 Sea- and lab- Nausea Relative risk reduction = 0.47* (95% delivery methods)1 induced confidence interval, 0.31 to 0.71) Dimenhydrinate2 16 Lab-induced Nausea symptom 60-point reduction in nausea score score (0 to 100) compared with 17-point reduction with placebo (P < .005)† Chlorpheniramine (4 mg 18 Lab-induced Rotating time, Increased rotating time in high- and low- and 12 mg)3 severe malaise dose groups; NNT = 4 in high-dose group (P = .01)‡ Cetirizine (Zyrtec), 18 Lab-induced Motion sickness No significant difference fexofenadine (Allegra)4 scores Ondansetron (Zofran) 605 Lab-induced Rotating time, No significant difference symptom scores 166 Sea-induced Symptom scores No significant difference Ginger (1 g powdered 79 Sea-induced Vomiting, cold NNT = 19 to prevent vomiting and cold root)7 sweats, nausea, sweats (P < .05)‡; no reduction in nausea vertigo or vertigo Ginger (1- or 2-g 18 Lab-induced 3-point nausea 1-point decrease in maximal nausea score capsules)8 score, time to (P < .05); 2.9- and 4.1-minute increase in onset of nausea time to onset of nausea (P < .05)† Ginger (940 mg powdered 36 Lab-induced Rotating time 4.1-minute increase (P < .001)† root)9 Ginger (500 to 1,000 mg 28 Lab-induced Severe malaise No significant difference powdered or fresh root)10

NNT = number needed to treat. *—Raw data not available for calculation of NNT. †—Continuous data; risk reductions and NNT not calculated. ‡—Confidence intervals were not reported. Information from references 1 through 10.

Recommendations from Others 4. Cheung BS, Heskin R, Hofer KD. Failure of cetirizine and fexofenadine to prevent motion sickness. Ann Pharmacother. 2003;37(2):173-177. Based on a summary of the evidence and expert opinion, 5. Muth ER, Elkins AN. High dose ondansetron for reducing motion UpToDate recommends the use of sedating antihis- sickness in highly susceptible subjects. Aviat Space Environ Med. tamines, scopolamine, or ginger for the treatment of 2007;78(7):686-692. 11 6. Hershkovitz D, Asna N, Shupak A, Kaminski G, Bar R, Tal D. Ondanse- motion sickness. tron for the prevention of seasickness in susceptible sailors: an evalua- tion at sea. Aviat Space Environ Med. 2009;80(7):643-646. Copyright Family Physicians Inquiries Network. Used with permission. 7. Grøntved A, Brask T, Kambskard J, Hentzer E. Ginger root against sea- Address correspondence to Matthew Sutton, MD, at msutton@unch. sickness. A controlled trial on the open sea. Acta Otolaryngol. 1988; unc.edu. Reprints are not available from the authors. 105(1-2):45-49. 8. Lien HC, Sun WM, Chen YH, Kim H, Hasler W, Owyang C. Effects of Author disclosure: No relevant financial affiliations to disclose. ginger on motion sickness and gastric slow-wave dysrhythmias induced by circular vection. Am J Physiol Gastrointest Liver Physiol. 2003; REFERENCES 284(3):G481-G489. 9. Mowrey DB, Clayson DE. Motion sickness, ginger, and psychophysics. 1. Spinks A, Wasiak J. Scopolamine (hyoscine) for preventing and treating Lancet. 1982;1(8273):655-657. motion sickness. Cochrane Database Syst Rev. 2011;(6):CD002851. 10. Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of ginger on motion 2. Pyykkö I, Schalén L, Jäntti V. Transdermally administered scopolamine sickness susceptibility and gastric function. Pharmacology. 1991; vs. dimenhydrinate. I. Effect on nausea and vertigo in experimentally 42(2):111-120. induced motion sickness. Acta Otolaryngol. 1985;99(5-6):588-596. 11. Priesol AJ. Motion sickness. UpToDate, Inc. http://www.uptodate.com/ 3. Buckey JC, Alvarenga D, Cole B, Rigas JR. Chlorpheniramine for motion contents/motion-sickness [subscription required]. Accessed May 14, sickness. J Vestib Res. 2004;14(1):53-61. 2012. ■

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