A 43-year-old woman sought advice about the treatment of her sea-sickness. A sea-kayaking enthusiast, she suffers disturbing motion sickness in big seas. The usual remedies have either been ineffective or made her drowsy. A scuba-diving instructor recommended that she try taking phenytoin the night before going kayaking, and she wonders whether there is any evidence to support this recommendation.

The primary search question was "Is phenytoin effective in the prevention of motion sickness?" The ideal studies to answer this question would be randomised controlled trials comparing phenytoin with placebo or comparing phenytoin with other conventional therapies.

I searched two online databases, MEDLINE and SUMSearch, combining the terms "motion sickness" and "phenytoin" and limiting the search to studies published in English. The MeSH term "motion sickness" covers a range of conditions, including sea-sickness and travel-sickness. I also searched the websites for two diving-related organisations: Divers Alert Network and Diving Medicine Online.

Five original research articles on the use of phenytoin for motion sickness were identified. Diving Medicine Online had a review article on motion sickness that mentioned phenytoin.

The first of the five research articles1 reported a laboratory-based placebo-controlled double-blind crossover study using simulated motion. The seven participants were given phenytoin at anticonvulsant levels. Phenytoin was found to be four times as effective as any other single agent in increasing tolerance to motion stress.

The second study2 involved 15 seamen and/or divers who worked for the US National Aeronautics and Space Administration in both small-boat trials (lasting one hour) and operational sea travel (lasting two to four days). Phenytoin was given in loading doses in the 24 hours before the trials and then maintained at anticonvulsant levels through regular serum testing and titrated doses. The small-boat phase of the study, a double-blind trial of phenytoin versus placebo, showed a significant reduction in nausea levels (P = 0.0172). The operational sea-travel phase of the study again showed a convincing advantage of phenytoin over placebo.

The third study,3 a small double-blind crossover study with nine participants, included sea travel as part of a series of exposures to rotational movement, again using the rapid-loading-dose approach to reach anticonvulsant plasma levels of phenytoin. Results showed that phenytoin effectively reduced motion sickness.

The fourth study4 focused on the effects of phenytoin on cognition and performance. Participants (n = 23) were given phenytoin to anticonvulsant levels or placebo. Phenytoin did not cause degradation in function, although at higher serum levels (beyond those required for efficacy) participants did report a number of subjective side effects (eg, lightheadedness).

The fifth study,5 with 35 participants, was a double-blind study comparing placebo with the use of a single 200 mg dose of phenytoin taken four hours before participants were spun round inside a rotating drum. While differences in the subjective scoring of symptoms were not significant, behavioural responses (vomiting, and request for early termination of the experiment) were significant (P < 0.05).

The review article on motion sickness in Diving Medicine Online6 described phenytoin being used the night before a dive, but did not indicate the evidence for this practice.

There is evidence that phenytoin is effective in preventing motion sickness. The approach used in most of the studies — that of rapidly loading subjects up to anticonvulsant levels of phenytoin in the preceding 24 hours and monitoring plasma levels — is hardly applicable for practical purposes. The generalisability of these studies is also questionable, as all were small and used healthy adult males. Taking a 200 mg dose of phenytoin four hours before exposure is practical, and the results are promising but not conclusive. Further research is required to determine the lowest effective dose. Short-term use of low doses is unlikely to produce serious problems. However, the fact that phenytoin is known to interact with some commonly used medications should be taken into account if it is to be prescribed for preventing sea-sickness.

The woman elected to try a single 200 mg dose of phenytoin four hours before going kayaking. This was considered the lowest dose that might prove effective, based on the available evidence. To test for side effects, the woman accepted my advice to try the first tablet on a day when she wouldn't be engaging in hazardous activity. (I can't report whether she was satisfied with the result, as I haven't heard from her since — that's the trouble with fit, healthy people!)