Canada Communicable Disease Report
Volume 29 ACS-11
15 November 2003

An Advisory Committee Statement (ACS) 
Committee to Advise on Tropical Medicine and Travel (CATMAT)*^†

STATEMENT ON MOTION SICKNESS

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Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides Health Canada with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. Health Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers. 

Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use. 

Definition and Etiology 

Motion sickness is known by many names, for example, car sickness, sea sickness, air sickness, space sickness, and motion maladaption syndrome. 

Motion sickness is a normal response to perception of motion when there is sensory conflict about body motion perceived by different receptors (visual, vestibular, and body proprioceptors). It can also be induced when the pattern of motion differs from that previously experienced, in the absence of expected motion, or when a person is viewing a very large screen but is not actually moving. 

Symptoms and Time Course 

The development of symptoms follows an orderly sequence that varies with the intensity of the stimulus and the susceptibility of the individual. The initial symptom is usually discomfort around the upper abdomen ("stomach awareness"), which is followed by nausea and increasing malaise. Concurrently, the face or area around the mouth becomes pale, and the individual starts to sweat. With rapid worsening of symptoms ("avalanche syndrome") there can be increased salivation, feelings of body warmth, a lightness of the head, and often depression and apathy. Vomiting typically follows. 

Additional symptoms are frequent but more variable. These include belching and flatulence, hyperventilation, sighing and yawning, headache, tightness around the forehead or a "buzzing" sensation, drowsiness, lethargy and somnolence, and panic or confusion. The lethargy, fatigue, and drowsiness can persist after the stimulus stops and nausea lessens. 

Over time, there is a tendency to adapt ("to get one's sea legs"). For most individuals this occurs by 2 to 3 days, although about 5% are said not to adapt and to remain symptomatic if the stimulus persists. Returning to stable circumstances, as in returning to shore, can trigger an exacerbation, but this is usually shorter because readaptation is quicker.

Incidence and Risk Factors 

The incidence of motion sickness varies, depending on the magnitude of the stimulus and the susceptibility of the individual. It ranges from < 1% on a large aircraft to almost 100% on a rough sea voyage under evacuation conditions. Boat travel is most likely to cause motion sickness, followed by travel by air, car, and train. 

Motion sickness is rare in those < 2 years of age. It is said to peak between the ages of 3 and 12, with a gradual decrease thereafter. Supporting data for this appear to be mainly anecdotal⁽¹⁾, and where data exist it is impossible to rule out self-selection as the reason for the observation⁽²⁾. Rates are higher among females than males (1.7:1) and increase during menstruation and pregnancy.

At a given level of stimulus, there are marked differences in natural susceptibility, which can be exacerbated by emotions like fear or anxiety, or by other illnesses, poor health, or some medications. Personal susceptibility tends to be a stable and enduring characteristic, and does not diminish with recurrent exposure^(3,4). 

Important physical characteristics of the stimulus include the frequency, intensity, and duration of directional changes. The risk of motion sickness is increased by visual stimuli, such as a moving horizon, or by zero gravity. 

Rates can be increased by other environmental factors, such as poor ventilation, odours, fumes, smoke, and carbon monoxide.

Differential Diagnosis and Complications 

The differential diagnosis includes vestibular disease, gastroenteritis, metabolic disorders, toxin exposures, and, at high altitudes, mountain sickness. Most symptoms attributed to motion sickness should resolve following termination of the motion stimulus or with adaptation to it. Some symptoms, such as lethargy, take longer to resolve⁽⁵⁾. Laboratory studies also show a delay in improvement in gastric motility, electroencephalographic studies, and test performance measures⁽⁶⁾. 

Complications are infrequent but include hypotension, dehydration, depression, and panic. 

Methodologies in Studies on Motion Sickness 

There are numerous methods used to assess medications and other measures directed against motion sickness, and all have deficiencies that weaken the ability to compare studies or to apply the information to the typical traveller⁽⁷⁾. The literature suggests that the average traveller has several options that generally are of equal benefit⁽⁸⁾. 

Many recommendations appear to be based on repeated but anecdotal observations made under real-life conditions. Where laboratory data exist, they are generally consistent with these observations.

There are a number of studies that use self-report data obtained by questionnaire, and these can involve large numbers of respondents. To facilitate completion, the questionnaire is usually simple and the responses are open to multiple interpretations. For example, in a study in which 98% of travellers (20 029 respondents) participated, there was a significant association between increased motion sickness and use of motion sickness medications, and between alcohol use and decreased motion sickness⁽²⁾. The investigators were unable to determine the temporal sequence or the effect of confounding factors. 

Most current controlled studies are conducted under laboratory conditions in which healthy, typically young male individuals are subjected to strong stimuli, e.g. a rotating chair, over a short time, with the aim of rapidly inducing some degree of motion sickness. These studies usually have a small number of subjects, and the results may not be relevant to the typical traveller, since they are usually used to study aspects of space sickness or effects under extreme sea conditions. 

Many older studies^(7,9), but few recent studies, have used more realistic settings, either in induced sea-like conditions or under real sea-based conditions⁽⁸⁾. It is almost impossible to control all key variables in these latter studies, but they may provide the most useful information. 

General Measures for Prevention of Motion Sickness 

Support for the following measures is based on observations from laboratory manipulations and repeated anecdotal experience. Scientific support is generally at level B II to B III (see Appendix)⁽¹⁰⁾. 

1. Minimize exposure:
   • be located in the middle of the plane or boat, where movement is least;
   • be in a semi-recumbent position;
   • minimize head and body movements.
     
     
2. Restrict visual activity:
   • fix vision on the horizon or some other stable, external object;
   • avoid fixation on a moving object;
   • avoid reading;
   • close eyes if below deck or in an enclosed cabin.
     
     
3. Improve ventilation and remove noxious stimuli.
   
   
4. Reduce the magnitude of the motion stimulus:
   • avoid or minimize acceleration and deceleration, and turning or moving of the vehicle.
     
     
5. Engage in distracting activity:
   • be in control of the vehicle;
   • perform mental activity.

Recommended dietary manipulations include decreasing large oral intakes, taking frequent small portions of food, and avoiding alcohol. The scientific support for these observations is less certain. 

Medications for Prevention of Motion Sickness 

1. Important variables 

There is no one, standard approach that is ideal for everyone in all circumstances. Important variables that may influence the choice include individual susceptibility, the amount of time available before the stimulus will start (e.g. planned travel versus a sudden exposure), the severity of the stimulus, the duration of the stimulus (e.g. a brief exposure versus a trip of several days or more), whether medications are being used for prophylaxis or as treatment once symptoms have begun, tolerance to individual medications, the need to maintain total alertness, and other underlying medical conditions. 

2. Potential routes of administration 

There are a variety of routes of administration. These include by mouth (tablet to swallow or chew), sublingual (tablet or sachet under tongue), buccal (sachet or tablet in mouth cavity), intramuscular, rectal (suppository), and transdermal (patch).

3. Timing of medication use 

Oral regimens must be taken before the exposure, both to allow absorption and to attain adequate levels of the medication. Regimens are usually considerably less effective once symptoms of motion sickness have begun. With the onset of symptoms absorption becomes less effective, and with vomiting becomes close to impossible. Once severe manifestations have begun, rectal suppositories may still be an option if intramuscular injections are not possible.

4. Classes of medications used 

Travellers commonly use two classes of centrally acting medications: muscarinic receptor antagonists and histamine H1-receptor antagonists. Despite intensive study, their site(s) of action remains poorly defined, and their effectiveness does not parallel their receptor-blocking potency. 

Under conditions of intense stimuli, there is a role for centrally acting sympathomimetic substances, e.g. dextroamphetamine⁽¹¹⁾. These are typically used in conjunction with either of the first two classes of agents. 

There are a number of other classes of agents that have been or are being studied and for which data are very conflicting (e.g. ginger^(12-15)), or preliminary (e.g. antidepressants and anticonvulsants). Much of the focus in the development of new compounds, such as doxepine⁽¹⁶⁾ and phenytoin^(17,18), is on decreasing adverse reactions, particularly those that could compromise functioning under conditions of space travel or maritime operations. 

Clinical trials investigating serotonin (5-HT3) receptor antagonist anti-emetics commonly used in cancer chemotherapy, such as ondansetron and granisetron, have not demonstrated their efficacy^(19-21); these medications are costly and cannot be recommended for the reduction of motion sickness.

5. Adverse reactions to medications used for motion sickness 

Motion sickness itself may contribute to some of the symptoms attributed to the medications, but drowsiness is common with all except those that include sympathomimetic agents. Symptoms are usually dose-related, and it may be possible to strike a balance between efficacy and adverse reactions (e.g. in most individuals scopolamine 0.3 mg will produce significant protection with minimal side effects). 

An interesting observation, particularly with long-acting agents,
is that, under stimuli that rarely produce motion sickness, the symptoms associated with the medication are likely to be worse than with placebo. In contrast, with progressively more intense symptoms of motion sickness, symptoms often attributed to the medication may be much more intense in placebo recipients^(22-24). 

6. Summary of reported results 

Table 1 lists common regimens that have been shown to be effective in one or more controlled trials. The level of evidence for their efficacy as compared with placebo is A I (see Appendix) for all. Much of the older literature on these regimens is summarized in references 7 and 9. 

The table includes information on the amount of time required to attain effective protection, the duration of the effectiveness, commonly experienced adverse reactions, and the severity of the motion for which it is likely to be most effective. None of the regimens is effective for everyone under all circumstances. 

Comments about individual medications, including their availability in Canada, dosage, and adverse reactions are given in Tables 1 and 2.

Table 1.    Effective oral regimens for the prevention of motion sickness 

*    Transdermal therapeutic system

Table 2.    Regimens available in Canada or the United States for the prevention of motion sickness 

*    Only available in injectable form
†    Transdermal therapeutic system

The intervals between doses and the recommendations for use in children and for use during pregnancy listed in Table 2 and discussed below are summarized from information in the literature and recommendations in standard reference texts such as Martindale⁽²⁵⁾ and the 2002 Compendium of Pharmaceuticals and Specialties⁽²⁶⁾. These sources of information are not always consistent and, particularly for use in pregnancy, are often not clear. Many of the agents are not recommended for use in young children. Since children < 2 years of age are said to rarely experience motion sickness, this restriction may not be of major practical significance. 

Compounds Used for Motion Sickness 

A. Dextroamphetamine 

Amphetamine and related agents have significant effects on motion sickness^(11,27). Their main usefulness appears to be under conditions of extreme stress, when they have been used in conjunction with scopolamine or promethazine to provide additional benefit and counteract adverse effects^(6,28,29). For prevention of motion sickness in the routine traveller, there is little indication for their use. In Canada, amphetamine is marketed as Dexedrine®, which is available as a short-acting and a long-lasting preparation. 

These agents are not recommended for use in pregnancy or in children < 3 years of age. If ever used for motion sickness prevention in childhood, the recommended dose for ages 3 to 5 years is one-quarter of the adult dose, and from ages 6 to 12 years is half the adult dose, which is 5 mg to 10 mg. 

Amphetamines are not routinely used, particularly on a repeated basis, because of their adverse reactions, which include restlessness and talkativeness, and the potential for abuse of these drugs. They interact with numerous medications, particularly those with cardiac or central nervous system effects. 

B. Cinnarizine (Rolab-cinnarizine®) 

In a dosage of 30 mg 1 to 2 hours before exposure and 15 mg every 6 to 8 hours thereafter, cinnarizine has been shown to be significantly more effective than a placebo⁽³⁾ and similar to scopolamine 0.3 mg every 6 to 8 hours in a much smaller study⁽³⁰⁾. The standard dose of 25 mg in tablet form is the one that was used in the study. It is not available in Canada but is in the United States.

Use of cinnarizine is not recommended in pregnancy, and no dosage recommendations are offered for those < 5 years. For children aged 5 to 12 years, half the adult dose is recommended. 

The major adverse reaction is drowsiness. 

C. Cyclizine (Valoid®) 

Cyclizine has been shown to be inferior to scopolamine but significantly better than a placebo⁽²⁴⁾. The standard dose is 50 mg orally every 4 to 6 hours. Cyclizine is available only as an intramuscular preparation in Canada (Marzine^®) but is available in the United States as an oral preparation (Valoid^®). 

Cyclizine is not recommended for use in pregnancy but can be used in children, for whom the recommended dose is ¼ of the adult dose up to age 6 years and ½ of the adult dose from 6 to 10 years of age. 

In recommended doses, the major adverse reaction to cyclizine is slight drowsiness. 

D. Dimenhydrinate (Gravol®) 

This has long been considered one of the treatments of choice for the degree of motion sickness that travellers might experience^(7,9,31-34). Dimenhydrinate is available under numerous trade names (e.g. Gravol^®) in over-the-counter preparations and comes as tablets, chewable tablets, filmkote preparations, long-acting capsules, liquid preparations, suppositories, and injectable preparations. 

Dimenhydrinate should not be used in children < 2 years of age and is not recommended for use in pregnancy. The standard adult dose is 50 mg to 100 mg orally every 4 to 6 hours, to a maximum of 400 mg in 24 hours. For children 2 to 6 years of age, the oral dose is 15 mg to 25 mg every 6 to 8 hours, to a maximum of 75 mg in 24 hours. For children 6 to 12 years of age, the oral dose is 25 mg to 50 mg every 6 to 8 hours, to a maximum of 150 mg in 24 hours. For children > 12 years of age, the oral dose is 50 mg every 4 to 6 hours, to a maximum of 300 mg in 24 hours. 

Compared with the scopolamine patch, dimenhydrinate's major deficiency is the need for frequent administration. The major adverse reactions are drowsiness and vertigo. In children there can be excitement. 

E. Meclizine (Bonamine®) 

Meclizine has also long been considered an effective regimen^(7,9,34) but does not appear to be as effective as the scopolamine patch⁽³⁵⁾. Meclizine (Bonamine^®) is available in a tablet that can be swallowed, chewed, or allowed to dissolve in the mouth. 

Meclizine is not recommended for use in pregnancy, but it can be used in children. The standard adult dose is 25 mg to 50 mg orally, but recommendations for dose intervals range from every 6 to 12 hours to every 12 to 24 hours. On the basis of the duration of action shown in Table 1, intervals longer than 12 hours would seem inappropriate if rough conditions are anticipated. Half the adult dose is recommended for children. 

The major adverse reaction is drowsiness. 

F. Promethazine (Phenergan®, Histantil®) 

Promethazine, with or without an amphetamine-like agent, has largely been used in situations of severe stimuli and for treatment of established motion sickness^(5,36). Promethazine is available in several brands (e.g. Phenergan^®), and as tablets and syrups. 

Promethazine can be used in pregnancy but should not be used in children < 2 years of age. The standard dose for prevention is 25 mg orally every 6 hours. Given its long duration of activity (Table 1), this frequency seems unnecessarily high. The dose recommended for children > 2 years of age is 0.25 to 0.5 mg/kg of body weight every 4 to 6 hours. 

Promethazine causes more drowsiness than most of the other standard agents, and its use is reported to result in significant decreases in performance scores of psychomotor function, information processing, and alertness. However, results are conflicting, and under conditions of motion sickness there may be less impairment than that attributable to the motion sickness itself⁽²⁸⁾. 

G. Scopolamine hydrochloride 

This preparation is not currently available on the Canadian or U.S. markets in an oral form. However, it is often the standard against which other medications have been compared^{(24,28,30,37)}. It is not apparent why oral scopolamine is not available, but presumably manufacturers believe that the scopolamine patch has replaced it. In Canada, there is a preparation, scopolamine butylbromide (Buscopan^®), which does not have an indication for motion sickness. 

The major adverse reactions to scopolamine are similar to those discussed for the scopolamine patch. 

H. Scopolamine patch (Transderm-V®) 

The scopolamine transdermal patch is applied to the skin behind the ear at least 8 hours before exposure to the stimulus and then replaced every 72 hours. It has been extensively studied and reviewed^(26,35). Studies show overall efficacy similar to that of scopolamine and dimenhydrinate given orally^{(31-33,35,37,38)}. Its main advantages are its practical ease of administration and long duration of activity. Problems include adverse reactions that may outweigh the benefit when there are minimal stimuli to induce motion sickness, the long period before onset of activity, and the inconsistency of effects in different individuals and in the same individual at different times^(26,39) . There is a concern that use of the patch may decrease adaptation to motion sickness, although this phenomenon has not always been consistently observed⁽²⁵⁾. The scopolamine patch (Transderm-V^®) is available in Canada. 

Use of the scopolamine patch is contraindicated in glaucoma and should be avoided in the young, the elderly, during pregnancy, and when there is urinary or pyloric obstruction. The scopolamine patch can interact with sedatives, such as antihistamines, alcohol, antidepressants, and anticholinergic agents, such as belladonna alkaloids. Hands should be washed after applying the patch to avoid inadvertent contact with the conjunctiva and resultant pupillary dilatation and blurred vision. Commonly reported adverse effects include dry mouth, drowsiness, and blurred vision (even without direct contact). The visual problem may increase with continuous use⁽²⁶⁾. Scopolamine can cause confusional states and/or visual hallucinations, particularly in elderly individuals.

Comparable Activity of Numerous Approaches 

A 1994 study assessed seasickness on a whale-watching trip, during which 80% without prophylaxis typically become sick. The study compared many of the available preparations that travellers might use⁽⁸⁾. The following regimens were taken up to 2 hours before departure: meclizine (12.5 mg) plus caffeine (50 mg), ginger root (250 mg), and cinnarizine (20 mg) plus domperidone (15 mg). Two regimens were started the night before: scopolamine patch and cinnarizine (25 mg) (with a second dose at least 1 hour before the trip). There were 1741 individuals recruited, and 1489 (85.5%) completed the evaluation. No significant differences were found among regimens, 4.1% to 10.2% of participants reporting vomiting and 16.4% to 23.5% reporting that they were at least slightly seasick. There was a slight trend towards the scopolamine patch having a weaker action (p = 0.14) and producing slightly more visual problems. The authors concluded that all but the scopolamine patch may be recommended for prophylaxis in this setting of short-term, but potentially intense, exposure.

Recommendations for Travellers Using Regimens Available in Canada 

The following are recommendations for preventive use by travellers who do not need to drive or perform skilled tasks and are restricted to medications available in Canada. All medications are effective compared with a placebo (A I [see Appendix]), but none will work for all travellers. If one approach is not effective or not tolerated, another should be tried.

There are no studies that definitively support or refute the following recommendations. Based on factors such as cost, willingness to tolerate adverse reactions, and prior experience, individual travellers may wish to choose one regimen over another. 

For longer-term travel (> 3 days), many travellers would find the scopolamine patch useful, but it has several disadvantages. The recommendation to use alternatives (see below*) as needed for mild stimuli is based on the observation that, with use of the patch, symptoms (adverse reactions) are more frequent than symptoms attributed to motion sickness when minimal or no rough conditions are encountered^(26,39). 

A. Short-term exposure (>= 6 hours) 

1. Mild to moderate stimulus
   • Recommended - dimenhydrinate
   • Alternatives - meclizine, promethazine
     
     
2. Intense stimulus
   • Recommended - promethazine plus amphetamine
   • Alternatives - dimenhydrinate, scopolamine patch

B. Longer-term exposure (> 6 hours) 

1. Mild stimulus
   • Recommended - dimenhydrinate as needed*
   • Alternatives - scopolamine patch, meclizine as needed*, promethazine as needed*
     
     
2. Moderate to intense stimulus
   • Recommended - scopolamine patch
   • Alternatives - repeated doses of dimenhydrinate, repeated doses of promethazine, repeated doses of meclizine

Treatment of Established Symptoms 

For treatment of established symptoms, options are more limited. Once vomiting has commenced, no oral regimen that is swallowed is likely to be effective⁽⁴⁰⁾. Intramuscular promethazine (25 mg to 50 mg) appears to be the most effective means of managing already developed severe motion sickness^(28,35,40), but most travellers will not be able to administer intramuscular injections. Rectal suppositories of dimenhydrinate are available. Several preparations can be dissolved in the mouth, but their effectiveness in the presence of vomiting is probably significantly compromised. 

If the exposure is likely to be prolonged, a scopolamine patch can also be applied⁽⁴¹⁾, but this will not provide immediate benefit. 

Alternative Approaches to Prevention of Motion Sickness 

Evidence for the effectiveness of acupressure, with the use of a commercially available product that applies pressure at a point above the wrist, has been shown to be equivocal⁽⁴⁾. There are observational studies^(4,42) that demonstrate conflicting results, and no large-scale clinical trials have been performed. 

Compounds like caffeine alone do not appear effective but may counteract some of the drowsiness seen with common agents like the antihistamines.

APPENDIX: STRENGTH AND QUALITY OF EVIDENCE SUMMARY* 

Categories for the strength of each recommendation

Categories for the quality of evidence on which recommendations are made

*    From: Macpherson DW⁽¹⁰⁾

References 

1. Cheung BSK, Money KE. The influence of age on susceptibility to motion sickness in monkeys. J Vestibular Res 1992;2:247-55. 

2. Lawther A, Griffin MJ. A survey of the occurrence of motion sickness amongst passengers at sea. Aviat Space Environ Med 1988;59:399-406. 

3. Hargreaves J. A double-blind placebo controlled study of cinnarizine in the prophylaxis of seasickness. Practitioner 1980;224:547-50. 

4. Warwick-Evans LA, Masters IJ, Redstone SB. A double-blind placebo controlled evaluation of acupressure in the treatment of motion sickness. Aviat Space Environ Med 1991;62:776-78. 

5. Graybiel A, Knepton J. Sopite syndrome: a sometimes sole manifestation of motion sickness. Aviat Space Environ Med 1976;47:873-82. 

6. Wood CD, Stewart JJ, Wood MJ et al. Therapeutic effects of antimotion sickness medications on the secondary symptoms of motion sickness. Aviat Space Environ Med 1990;61:157-61. 

7. Brand JJ, Perry WLM. Drugs used in motion sickness. Pharmac Rev 1966;18:895-924. 

8. Schmid R, Schick T, Steffen R et al. Comparison of seven commonly used agents for prophylaxis of seasickness. J Travel Med 1994;1:203-06. 

9. Wood CD, Kennedy RE, Graybiel A et al. Clinical effectiveness of antimotion sickness drugs. JAMA 1966;198:1155-58. 

10. MacPherson DW. Evidence-based medicine. CCDR 1994;20:145-47. 

11. Kohl RL, Calkins DS, Mandell AJ. Arousal and stability: the effects of five new sympathomimetic drugs suggest a new principle for the prevention of space motion sickness. Aviat Space Environ Med 1986;57:137-43. 

12. Grontved A, Brask T, Kambskard J et al. Ginger root against seasickness: a controlled trial on the open sea. Acta Otolaryngol 1988;105:45-49. 

13. Holtmann S, Clarke AH, Scherer H et al. The anti-motion sickness mechanism of ginger: a comparative study with placebo and dimenhydrinate. Acta Otolaryngol 1989;108:168-74. 

14. Mowrey DB, Clayson DE. Motion sickness, ginger, and psychophysics. Lancet 1982;1:655-57. 

15. Stewart JJ, Wood MJ, Wood CD et al. Effects of ginger on motion sickness susceptibility and gastric function. Pharmacol 1991;42:111-20. 

16. Kohl RL, Sandoz GR, Reschke MF et al. Facilitation of adaptation and acute tolerance to stressful sensory input by doxepin and scopolamine plus amphetamine. J Clin Pharmacol 1993;33:1092-1103. 

17. Chelen W, Ahmed N, Kabrisky M et al. Computerized task battery assessment of cognitive and performance effects of acute phenytoin motion sickness therapy. Aviat Space Environ Med 1993;64:201-05. 

18. Woodard D, Knox G, Myers KJ et al. Phenytoin as a countermeasure for motion sickness in NASA maritime operations. Aviat Space Environ Med 1993;64:363-66. 

19. Levine ME, Chillas JC, Stern RM et al. The effects of serotonin (5-HT3) receptor antagonists on gastric tachyarrhythmia and the symptoms of motion sickness. Aviat Space Environ Med 2000;71:1111-14. 

20. Reid K, Palmer JL, Wright RJ et al. Comparison of the neurokinin-1 antagonist GR205171, alone and in combination with the 5-HT3 antagonist ondansetron, hyoscine and placebo in the prevention of motion-induced nausea in man. Brit J Clin Pharm 2000;50:61-4. 

21. Stott JRR, Barnes GR, Wright RJ et al. The effect on motion sickness and oculomotor function of GR 38032F, a 5-HT3-receptor antagonist with anti-emetic properties. Brit J Clin Pharm 1989;27:147-57. 

22. Brand JJ, Colquhoun WP, Gould AH et al. Hyoscine and cyclizine as motion sickness remedies. Brit J Pharmacol 1967;30:463-69. 

23. How J, Lee PS, Seet LC et al. The republic of Singapore Navy's Scopoderm TSS study: results after 2,200 man-days at sea. Aviat Space Environ Med 1988;59:646-50. 

24. Parrott AC. Transdermal scopolamine: a review of its effects upon motion sickness, psychological performance, and physiological functioning. Aviat Space Environ Med 1989;60:1-9. 

25. Martindale: The Complete Drug Reference, 33^rd ed. London: Pharmaceutical Press, 2002. 

26. Canadian Pharmaceutical Association. Compendium of Pharmaceuticals and Specialties, 37th ed. Ottawa: CPA, 2002. 

27. Kohl RL, MacDonald S. New pharmacologic approaches to the prevention of space/motion sickness. J Clin Pharmacol 1991;31:934-46. 

28. Wood CD, Manno JE, Manno BR et al. Side effects of antimotion sickness drugs. Aviat Space Environ Med 1984;55:113-16. 

29. Wood CD, Stewart JJ, Wood MJ et al. Effectiveness and duration of intramuscular antimotion sickness medications. J Clin Pharmacol 1992;32:1008-12. 

30. Hargreaves J. The prophylaxis of seasickness. A comparison of cinnarizine with hyoscine. Practitioner 1982;226:160. 

31. McCauley ME, Royal JW, Shaw JE et al. Effect of transdermally administered scopolamine in preventing motion sickness. Aviat Space Environ Med 1979;50:1108-11. 

32. Price NM, Schmitt LG, McGuire J et al. Transdermal scopolamine in the prevention of motion sickness at sea. Clin Pharmacol Ther 1981;29:414-19. 

33. Pyykko I, Schalen L, Jantti V. Transdermally administered scopolamine vs dimenhydrinate: I. Effect on nausea and vertigo in experimentally induced motion sickness. Acta Otolaryngol (Stockh) 1985;99:588-96. 

34. Wood CD, Graybiel A. Evaluation of 16 anti-motion sickness drugs under controlled laboratory conditions. Aerospace Med 1968;39:1341-44. 

35. Clissold SP, Heel RC. Transdermal hyoscine (scopolamine): a preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1985;29:189-207. 

36. Davis JR, Jennings RT, Beck BG et al. Treatment efficacy of intramuscular promethazine for space motion sickness. Aviat Space Environ Med 1993;64:230-33. 

37. Uijtdehaage SHJ, Stern RM, Koch KL. Effects of scopolamine on autonomic profiles underlying motion sickness susceptibility. Aviat Space Environ Med 1993;64:1-8. 

38. Noy S, Shapira S, Zilbiger A et al. Transdermal therapeutic system scopolamine (TTSS), dimenhydrinate, and placebo — a comparative study at sea. Aviat Space Environ Med 1984;55:1051-54. 

39. Homick JL, Kohl RL, Reschke MF et al. Transdermal scopolamine in the prevention of motion sickness: evaluation of the time course of efficacy. Aviat Space Environ Med 1983;54:994-1000. 

40. Graybiel A, Lackner JR. Treatment of severe motion sickness with antimotion sickness drug injections. Aviat Space Environ Med 1987;58:773-76. 

41. Landolt JP, Monaco C. Seasickness in totally enclosed motor-propelled survival craft: remedial measures. Aviat Space Environ Med 1992;63:219-15. 

42. Stern RM, Jokerst MD, Muth ER et al. Acupressure relieves the symptoms of motion sickness and reduces abnormal gastric activity. Alt Ther Health Med 2001;7:91-4.

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