Antimalarial chemoprophylaxis and the risk of neuropsychiatric disorders

Background: Case reports and epidemiological studies have associated the use of mefloquine with neuropsychiatric adverse events. Methods: We used the General Practice Research Database to conduct a follow-up study with a nested case control analysis. We assessed the risk of developing first-time anxiety, stress-related disorders/psychosis, depression, epilepsy or peripheral neuropathies in patients using mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil for malaria chemoprophylaxis, as compared to unexposed travelers. Results: Compared to non-users of antimalarials, the adjusted odds ratio in the nested case control analysis for users of mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil were 0.71 (95% CI 0.56-0.90), 1.04 (95% CI 0.74-1.46), and 0.73 (95% CI 0.61-0.86) for anxiety or stress-related disorders combined, 0.54 (95% CI 0.41-0.71), 1.06 (95% Cl 0.71-1.59), and 0.75 (95% CI 0.62-0.91) for depression, 0.69 (95% Cl 0.35-1.36), 1.41 (95% CI 0.54-3.67), and 0.75 (95% CI 0.42-1.36) for epilepsy, and 1.22 (95% CI 0.50-2.99), 1.59 (95% CI 0.41-6.15), and 1.05 (95% CI 0.54-2.03) for neuropathies, respectively. The risk of all outcomes was higher in females than in males across all exposure categories. Conclusions: The risk of neuropsychiatric disorders was similar for users and for non-users of antimalarial chemoprophylaxis, with evidence for elevated risks in some subgroups. (C) 2013 Elsevier Ltd. All rights reserved.