Acute and long-term psychiatric side effects of mefloquine: A follow-up on Danish adverse event reports
Section snippets
Background
Mefloquine is a cost effective drug for prophylaxis and treatment of Plasmodium falciparum malaria and has been available as a chemoprophylaxis since 1985 [1], [2]. Initial clinical trials indicated that side effects were mild [3], [4], [5], and serious adverse events were rarely observed [6]. A double-blinded, randomized study compared adverse reactions between mefloquine and other anti-malaria prophylaxis regimes and did not find a significant difference between the different anti-malarials
Study population
The Danish National Drug Authority, Committee of Adverse Drug Reactions, gave access to all reports of adverse events associated with mefloquine received between January 1.1996 and August 1.2000, 95 reports in all (see Fig. 1). With one exception, written consent to contact each case were obtained from the physicians who had been reporting the side effects. One person had been reported twice, thus 93 cases were considered for inclusion in the study. Four persons were under the age of 18, and
The initial adverse events reports
The 73 initial reports of mefloquine adverse event reports filed to The Danish National Drug Authority, Committee of Adverse Drug Reactions included the following complaints; 45 subjects reported physical symptoms (including neurological), 27 concerned signs of anxiety (“neurosis” was coded as anxiety), 26 reported sleep disturbances (including nightmares), 18 dealt with depression/feeling low, 11 reports concerned signs of a possible psychotic states (delusions/hallucinations), cognitive
Discussion
This is the first larger comparative study of long term psychiatric outcome following mefloquine associated adverse events. Using the SF-36, we found significantly poorer results for the subscales vitality (VT), role emotional (RE), and mental health (MH) in a group with previously reported acute side effects to mefloquine compared to a matched control population. Also, 30 out of the 73 subjects reported that the symptoms of mental problems they had indicated in SCL-90-R lasted more than 9
Conclusions
Although it is not concluded that mefloquine results in more neuropsychiatric adverse events than other antimalarials, this study does give some support to the possible development of long-term mental health problems after mefloquine associated adverse events. It also gives a comprehensive clinically oriented picture of the spectrum of possible psychiatric problems in the acute phase. Future research should eliminate other explanations for the observed side effects, clarify possible
Conflict of interest
None of the authors declared any conflicts of interests. The study did not receive support from the manufacture of mefloquine (Hoffman-La Roche, Basel, Schwitzerland). The initial statistical analysis was performed at Statens Serum Insitute and completed at Psychiatric Center North Zealand, Psychiatric Research Unit, University of Copenhagen, Hillerød, Denmark.
Acknowledgment
The authors would like to acknowledge Mats Lindström and Kim Theilgaard-Mönch for their review of this manuscript.
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