Neuropsychiatric manifestations after mefloquine therapy for Plasmodium falciparum malaria: comparing a retrospective and a prospective study

Trop Med Int Health. 1998 Feb;3(2):83-8. doi: 10.1046/j.1365-3156.1998.00163.x.


Mefloquine has been increasingly used for treatment of chloroquine-resistant malaria since its introduction in the late 1970s. In 1987 the first case of toxic encephalopathy was published, and in 1989 the WHO initiated reporting and investigation of neuropsychiatric adverse reactions of mefloquine. Neuropsychiatric adverse drug reactions are now well documented. We compared an open prospective 3 year study including all patients with P. falciparum treated with mefloquine with an earlier published, retrospective study on a comparable population from our department covering the period up to 1989. In the retrospective study neuropsychiatric adverse effects were not specifically asked for, while in the prospective study possible adverse reactions were registered daily according to a specified questionnaire. No case of neuropsychiatric adverse reaction was registered in the retrospective study. In the prospective study, 28% had one or more neuropsychiatric adverse reactions, although severity was mostly mild to moderate. Other adverse reactions occurred in 96% in the retrospective study compared to 81% in the prospective study.

In conclusion: one often finds only what one looks for, e.g adverse events may be overlooked for a decade, if relatively uncommon. This report also shows that retro- and prospective studies may give very different results.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Antimalarials / adverse effects*
  • Bias
  • Female
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Male
  • Mefloquine / adverse effects*
  • Mental Disorders / chemically induced*
  • Nervous System Diseases / chemically induced*
  • Prevalence
  • Prospective Studies
  • Research Design / standards*
  • Retrospective Studies
  • Surveys and Questionnaires


  • Antimalarials
  • Mefloquine