[Prevention of motion sickness with a transdermal therapeutic system containing scopolamine. A randomized, comparative double-blind study in the German Federal Navy]. Influence of transdermal scopolamine on motion sickness during 7 days' exposure to heavy seas. Drug treatment of motion sickness: scopolamine alone and combined with ephedrine in real and simulated situations. Side-effects of 1-hyoscine and cyclizine studied by objective tests. Psychomotor, physiological and cognitive effects of scopolamine and ephedrine in healthy man. The Republic of Singapore Navy's Scopoderm TTS study: results after 2,200 man-days at sea. [Comparative in-flight study of a scopolamine-containing membrane plaster versus dimenhydrinate under defined acceleration conditions]. Transdermal scopolamine in the prevention of motion sickness at sea. Stimulation of the semicircular canals via the rotary chair as a means to test pharmacologic countermeasures for space motion sickness.
To test the prophylactic value of anti-motion sickness drugs, a randomized double-blind trial was undertaken on 46 young, healthy, male volunteer marines. Comparison was made between a transdermal therapeutic system (TTS) containing as the effective agent scopolamine (TTS-scopolamine) and proprietary meclozine tablets. An artificial "sea voyage" served to produce motion sickness, each subject sitting by himself on an artificially tilting "island", on two days for 30 minutes. Without treatment, 19 of the 46 subjects developed symptoms of motion sickness requiring treatment. After administration of TTS-scopolamine or meclozine tablets (double-dummy technique) the motion sickness score was reduced by 89% and 59%, respectively. There was a reduction on the visual analog scale of 98% and 59%, respectively. Probability of error (Fisher's exact probability test) for assuming therapeutic advantage of TTS-scopolamine over meclozine tablets was 13.5%. A pre-set significance level of 5% was thus not reached. This trial shows that TTS-scopolamine, even in a brief exposure, has at least the same effectiveness as meclozine, in addition to avoiding the gastrointestinal tract and maintaining with certainty a constant blood level over three days. We conducted a double-blind, placebo-controlled study to evaluate the efficacy and tolerability of transdermal scopolamine in the prevention of motion sickness (MS) aboard a frigate during 7 days of continuously moderate or heavy seas. Forty-nine healthy sailors with a previous history of MS were randomly assigned to receive a transdermal therapeutic system of scopolamine (TTS-S) or transdermal placebo (TD-P). Patches were placed behind the ears at least 4 hours before departure and were removed 72 hours later. Subjects were observed on days 1 to 4 and 6. In the TTS-S group, both subjective feeling of MS and the incidence of nausea were reduced during the first 2 days. Because of adaptation, differences in signs and symptoms of MS between subjects receiving TTS-S and TD-P disappeared after the second day. During the first 3 days, vomiting occurred less often in the TTS-S group. On day 6, 3 days after removal of the patch, vomiting occurred in 23% of the TTS-S group, probably due to delay in adaptation, but none of the subjects in the TD-P group vomited. Concentration was not adversely influenced, since the ability to work increased in the TTS-S group. During prolonged continuous exposure to heavy and moderate seas, 2.5 cm2 TTS-S discs proved to be efficacious in preventing MS, with xerostomia as a tolerable side effect and no significant ocular side effects. In two placebo-controlled, double-blind, randomized trials scopolamine (0.3 mg) alone or combined with ephedrine (25 mg) was tested for its effectiveness in the prevention of seasickness during 24 h at sea and of motion sickness in rotating chair tests in a laboratory. Scopolamine was effective both alone and in combination with ephedrine, which supports the hypothesis on central cholinergic overactivity in the pathogenesis of motion sickness. Ephedrine did not markedly increase the effectiveness of scopolamine. Side-effects were slight and did not disturb the operating ability of the volunteers. nan Three placebo-controlled double-blind studies in healthy volunteers were performed to reveal the psychophysiological effects of scopolamine, ephedrine and their combination. Single intravenous dose of scopolamine 6 micrograms/kg (scopolamine hydrobromide 7.4 micrograms/kg) impaired various psychomotor functions both subjectively and objectively. It caused sedation, impairment of coordinative and reactive skills, visual disturbances and impairment of shortterm memory. Oral scopolamine hydrobromide in single doses of 0.3 mg and 0.9 mg, or 0.9 mg b.d. for 3 days, had few effects. A slight impairment of shortterm memory and a decrease in the flicker fusion threshold were seen. The visual nearpoint and pupil diameter were increased and some subjects reported blurred vision and dizziness during treatment with scopolamine 0.9 mg b.d. Scopolamine showed clear cardiovascular effects in all studies: it decreased heart rate and systolic blood pressure. Ephedrine alone and in combination with scopolamine had no deleterious effects. On the contrary, it antagonized the scopolamine-induced impairment in the flicker fusion test and the decrease in blood pressure and heart rate. In sufficient doses scopolamine impairs various psychomotor and cognitive skills. An oral dose of scopolamine hydrobromide 0.9 mg on average has few effects, although they may be very striking in certain individuals. To avoid unwanted effects and diminution in performance by scopolamine, doses less than 0.9 mg should be used. Most clinical trials investigating prevention of seasickness with transdermal scopolamine have been short-term, and little information regarding long-term use is available. We report here a double-blind trial conducted on board a flat-bottomed Republic of Singapore Navy vessel of 2,490 tons, sailing in the South China Sea. The trip lasted 26 d, but self-assessment by the 122 adult male participants (using a simplified scale quantifying the level of seasickness) was confined to the 18 d spent at sea. We found that the protection rate with transdermal scopolamine was 46-57%, with maximum benefits to inexperienced participants, during the early preadaptation phase, or in rough seas even after adaptation. Unwanted effects were few and generally minor. We concluded that the benefits of Scopoderm were worth exploiting even for long trips in moderate-to-rough seas. The efficacy and tolerability of Scopoderm TTS (SCOTTS), a transdermal system containing scopolamine, were compared with those of the oral antiemetic dimenhydrinate (double-dummy technique) in a controlled, double-blind, within-patient study including 20 test persons with proven motion sickness. During a 1-h test flight, SCOTTS proved to be as effective as dimenhydrinate. The efficacy and tolerability of both SCOTTS and dimenhydrinate were assessed as to be equally good. Due to its galenic properties, SCOTTS is effective over a 72-h period and therefore is useful in the prevention of motion sickness during long-distance flights, where it is superior to dimenhydrinate. Studies were conducted to evaluate the efficacy of scopolamine, absorbed through intact skin, in preventing motion sickness at sea. Efficacy of transdermal scopolamine was compared with oral dimenhydrinate and placebo. Transdermal applications were made 4 to 16 hr before exposure to motion. Dimenhydrinate or placebo was given 1.5 hr before motion and again 2.5 hr after motion began. Comparison with placebo indicated that transdermal scopolamine provided protection against motion sickness at a significance level of p = 0.0001 and oral dimenhydrinate at a level of p = 0.05. Dry mouth, drowsiness, and blurred vision associated with transdermal scopolamine therapy were minimal. Space motion sickness is currently treated pharmacologically with the empiric use of the H1 antihistamine promethazine, but use of this intervention is limited by the side effect of significant sedation. This creates a dilemma, as full cognition is particularly important during the same conditions likely to exacerbate the symptoms of space motion sickness. Using overstimulation of the semicircular canals with a rotary chair as a paradigm for space motion sickness, we evaluated four medications, commonly used for the treatment of terrestrial motion sickness and vertigo, for their efficacy in alleviating the simulated symptoms of space motion sickness.
                Randomized, prospective, double-blind study.
                Tertiary referral center.
                Healthy male and female volunteers, 18 years of age or older, without history of neurologic or psychiatric disorders, and with no known allergies or any previous adverse reactions to the drugs used.
                Lorazepam 1 mg, meclizine 25 mg, promethazine 25 mg, scopolamine 0.4 mg, or placebo.
                The ability of each treatment to control the nausea and vomiting associated with our paradigm for space motion sickness was evaluated by measuring time of rotation pre- and posttreatment and time of symptom onset pre-and posttreatment.
                Only scopolamine effected a mean change in duration of rotation that reached statistical significance when compared with placebo (p <0.008), with a greater than 40% increase in rotation time. Results with promethazine were not statistically significant.
                Results showed a rank order of efficacy of scopolamine > promethazine > placebo > meclizine > lorazepam. Scopolamine significantly increased rotation time, but none of the treatments resulted in a significant delay to onset of symptoms.
The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective. No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists. In addition, we identified no randomised controlled trials that examined the effectiveness of scopolamine in the treatment of established symptoms of motion sickness.