Neurological, cardiovascular and metabolic effects of mefloquine in healthy volunteers: a double-blind, placebo-controlled trial.

1. To assess neurological, cardiovascular, metabolic and other side-effects of mefloquine given in conventional prophylactic dose to healthy volunteers, a double-blind, randomized, placebo-controlled trial was conducted. In addition, the identity of the active drug was concealed until the end of the trial. 2. A total of 106 healthy adults were recruited, of whom 95 (mean age 24 years; 45% males) completed the full study protocol. 3. Subjects had a baseline assessment, received placebo as first dose, were randomized to mefloquine 250 mg or placebo weekly for 4 weeks starting a week later, and were reassessed after the 2nd and 4th active/placebo doses. Subjects kept a daily symptom diary from 2 weeks before until 2 weeks after the dosing period. 4. Plasma mefloquine assay suggested compliance in all 46 subjects allocated active treatment (week 5 mean +/- s.d.; 2.35 +/- 0.94 mumol l-1. Mefloquine did not alter calcium homoeostasis but produced a mean 0.5 mmol l-1 fall in serum glucose over the study period (P < 0.001) and relative hyperinsulinaemia. Symbol digit modalities, and digit forwards and backwards test scores, were similar in active and placebo groups across the three assessments, as were lying/standing blood pressure and high-tone hearing loss. Electrocardiographic QTc interval prolongation and diarrhoea were mild but transient side-effects of mefloquine (P < 0.01). Neurological symptoms were comparable in the two groups throughout the study. There was no evidence of drug toxicity in 11 subjects who withdrew. 5. Mefloquine prophylaxis does not appear to produce low-grade but debilitating neurological symptoms or to alter the results of sensitive tests of cerebral function. However, there may be situations in which mefloquine might contribute to hypoglycaemia and cardiac dysrhythmias.

RCT Entities:   Population Interventions Outcomes