A Comparison of Intranasal and Oral Scopolamine for Motion Sickness Prevention in Military Personnel

Abstract

Executive SummaryMotion sickness in astronauts, aviators, and military personnel often leads to decrements in operational performance. The anti-motion sickness medication, scopolamine, is effective; however, oral and transdermal administrations have proven problematic due to slow absorption, low bioavailability, unpredictable therapeutic effect, potential medication loss due to emesis, and side effects. Although efficacy and side-effect characteristics of intranasally administered scopolamine have not been established, results from preliminary studies indicate intranasal scopolamine has faster absorption, higher bioavailability, and a more reliable therapeutic index than equivalent oral or transdermal forms. The purpose of this study was to compare the efficacy, side-effect profile, and pharmacotherapeutics of a 0.4 mg dose of intranasal scopolamine gel and a 0.8 mg dose of oral scopolamine. It was hypothesized that intranasal delivery of scopolamine would rapidly achieve therapeutic concentrations at lower doses compared to oral scopolamine while minimizing medication-induced performance impairment. To test these hypotheses, 54 aviation candidates, 50 male and 4 female, were recruited and randomized to one of three treatment groups [intranasal scopolamine gel (IN SCOP); oral scopolamine (PO SCOP); or placebo] and then exposed to passive Coriolis cross-coupling for 40 minutes or until moderate nausea was reported. Medication efficacy was determined by number of head movements tolerated among groups and pharmacotherapeutics for IN SCOP and PO SCOP were determined by salivary assay. Side-effect profiles for all groups were derived from performance on a cognitive battery, measurements of near-focus visual accommodation (VA), scores on the Karolinska Sleepiness Scale (KSS) and motion sickness questionnaires. Analysis detected no significant differences in the number of head movements tolerated among groups, p > 0.05. Pharmacotherapeutic data show increased scopolamine absorption and decreased time to reach maximum salivary concentration with intranasal administration (T max = 1.463 ± 0.98 hr, C max = 54.857± 103.739 ng/mL, AUC = 51.732 ± 93.802 ng*h/mL). No treatment effects were detected over time on the cognitive battery, VA, or KSS, p > 0.05. An ANOVA revealed a significant decrease in heart rate over time for IN SCOP and PO SCOP versus placebo at several time points post-dose, while no clinically significant differences were found for systolic or diastolic blood pressures. A negative linear relationship was found between Motion Sickness Susceptibility Questionnaire (MSSQ) scores and number of head movements (r = -.24, p < .05). The present study lacked sufficient power to draw definitive conclusions regarding efficacy or to make adequate comparisons between the two medications, F (2, 50) = 0.743, p > .05, observed power = 17 %, however; medication absorption was significantly greater for IN SCOP at onehalf the dose (0.4 mg v. 0.8 mg) with no side effects or detrimental impact to performance. 3 Introduction Impac...