Antimalarial chemoprophylaxis and the risk of neuropsychiatric disorders

Case reports and epidemiological studies have associated the use of mefloquine with neuropsychiatric adverse events.

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.

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% CI 0.71-1.59), and 0.75 (95% CI 0.62-0.91) for depression, 0.69 (95% CI 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.

The risk of neuropsychiatric disorders was similar for users and for non-users of anti-malarial chemoprophylaxis, with evidence for elevated risks in some subgroups.