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Schlagenhaue and colleagues performed a double-blind, randomized, placebo-controlled cross-over trial to evaluate the effect of mefloquine on performance of pilots in training. Twenty-two of the 23 were men, and exclusion criteria included a history of seizure disorder, psychosis or severe depression, use of a cardiovascular medication, impaired renal or hepatic function, and the use of hypnotics or tranquilizers within two weeks or alcohol within 12 hours of testing. In order to achieve steady state rapidly, 250 mg mefloquine or matching placebo was administered daily for three consecutive days and then weekly for three consecutive weeks. The washout period prior to crossover was 4-6 months in order to adequately accommodate the long terminal half-life (18 days) of mefloquine.
One subject withdrew during loading with mefloquine because of dizziness, diarrhea, and flu-like symptoms; three others reported sleep disturbance during mefloquine loading but did not withdraw. During steady state administration, there was no significant difference between mefloquine and placebo periods with regard to flight performance (using a flight simulator), psychomotor function, "postural sway," neurobehavioral function, sleep parameters, or mood.
Many individuals planning trips to malaria endemic areas are afraid to take mefloquine prophylaxis because of reported adverse experiences of others. Unfortunately, in many areas, including both East and West Africa, mefloquine is the preferred chemoprophylactic. Furthermore, retrospective studies have demonstrated the tolerability of mefloquine in both tourists and in Peace Corps workers, with the latter individuals commonly receiving mefloquine continuously for more than a year (Steffen R, et al. Lancet 1993;341:1299-1303; Lobel HO, et al. Lancet 1993;341: 848-851). A more recent retrospective questionnaire study reported that, although there was not a greater overall incidence of adverse effects, there was a somewhat higher incidence of moderate or severe neuropsychiatric side effects associated with mefloquine than with chloroquine plus proguanil use (0.7% vs 0.09%) (Barrett PJ, et al. BMJ 1996;313:525-528). However, the retrospective nature of the study, the subjective nature of these complaints, and the strong likelihood of ascertainment bias make even that result suspect.
The study reviewed here is by far the most carefully performed prospective study examining the issue of the tolerability of mefloquine prophylaxis. The population studied, potential airplane pilots, is important because they currently are advised not to use mefloquine prophylaxis for fear that it will interfere with their professional performance. This study fails to demonstrate, despite the use of very sophisticated methodology, any such adverse effect.
As indicated by the authors, a previous study failed to demonstrate an adverse effect of mefloquine administration on driving performance of normal volunteers whether administered with or without alcohol (Vurman E, et al. Eur J Clin Pharmacol 1996;50:475-482). This study, and that of Schlagenhaue et al, thus provide strong evidence of the safety of mefloquine in selected healthy adult volunteers. Further data examining subjects who are not as young or as healthy would be welcome. Nonetheless, these studies support the use of mefloquine for malaria prophylaxis when indicated.