PHARMACODYNAMICS M. M. van Riemsdijk · M. M. van der Klauw · J. A. C. van Heest F. R. Reedeker · R. J. Ligthelm · R. M. C. Herings · B. H. Ch. Stricker Neuro-psychiatric effects of antimalarials Abstract Objective: To study the neuro-psychiatric ad- verse eﬀects of antimalarial drugs. Setting: Persons who visited a Travel Clinic in Rotter- dam over a period of 3 months. Design: Prospective cohort study on 394 persons taking meﬂoquine, 493 persons taking proguanil and 340 per- sons not taking antimalarial drugs who visited Africa, South America, Asia, or the Middle East. Methods: All persons received a structured questionnaire within 14 days of their return to the Netherlands. The questionnaire consisted of questions regarding use of alcohol, smoking, general health, medical history, trop- ical diseases during the trip, and other medicines, and contained an extensive list of general complaints re- garding all body systems at four levels of severity. A modiﬁed and validated version of the Proﬁle of Mood States was included. Results: In the study period, 2541 persons visited the Travel Clinic, of whom 1791 (70%) were both eligible and willing to co-operate. Of these 1791, data were ob- tained from 1501 (84%). Insomnia was most frequently encountered in users of meﬂoquine and mouth ulcers in proguanil users. After adjustment for gender, age, des- tination, and alcohol use, the relative risk for insomnia to meﬂoquine versus non-users of antimalarials was 1.6, and the excess risk was 6 per 100 users over an average period of 2 months. There were no signiﬁcant diﬀerences between groups in depression, anxiety, agitation, and confusion. Stratiﬁcation by gender demonstrated that insomnia was more common in women on meﬂoquine, but not in men. Also, women more frequently men- tioned palpitations as an adverse event. After adjust- ment for age, destination, and alcohol use in women, the relative risks for insomnia and palpitations to me- ﬂoquine versus non-use of antimalarials were 2.4, and 22.5, respectively. When travellers were speciﬁcally asked for the adverse reactions they had experienced, anxiety, vertigo, agitation, and nightmares were signiﬁ- cantly more frequently mentioned by meﬂoquine users. Conclusion: Insomnia was more commonly encountered during use of meﬂoquine than proguanil or during non- use of antimalarials. Key words Cohort study, Meﬂoquine, Proguanil, Psy- chic adverse eﬀects, Antimalarial drugs Introduction Meﬂoquine is a quinoline derivative which is used for the treatment and prophylaxis of several forms of ma- laria. It is mainly used for prophylaxis against Plasm- odium falciparum, in areas in which the parasite is resistant to chloroquine and proguanil. Meﬂoquine is predominantly used in a weekly dose of 250 mg. The most frequently encountered adverse reactions are nau- sea, abdominal pain, and dizziness. After therapeutic use of meﬂoquine, often as 1.5 g in three administrations, neuro-psychiatric adverse eﬀects have been noted [1]. Similar cases after both therapeutic and prophylactic treatment with meﬂoquine have been reported in the medical literature on several occasions [2–13], but few data exist on the frequency of neuro-psychiatric eﬀects to meﬂoquine and other antimalarials. In this prospec- tive cohort study, we investigated the occurrence of adverse events to antimalarials in travellers. We were especially interested in the frequency of mild neuropsy- chiatric adverse events to meﬂoquine in comparison to non-users of antimalarials. Eur J Clin Pharmacol (1997) 52: 1–6  Springer-Verlag 1997 M.M. van Riemsdijk · B.H.Ch. Stricker (&) Pharmaco-epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical School, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands M.M. van der Klauw · J.A.C. van Heest Drug Safety Unit, Inspectorate for Health Care, Rijswijk, The Netherlands F.R. Reedeker · R.J. Ligthelm Travel Clinic, Havenziekenhuis, Rotterdam, The Netherlands R.M.C. Herings Department of Pharmacoepidemiology and Pharmacotherapy, University of Utrecht, The Netherlands