Elsevier

Travel Medicine and Infectious Disease

Volume 13, Issue 1, January–February 2015, Pages 80-88
Travel Medicine and Infectious Disease

Acute and long-term psychiatric side effects of mefloquine: A follow-up on Danish adverse event reports

https://doi.org/10.1016/j.tmaid.2014.10.021Get rights and content

Summary

Background

The aim of the study was to explore the profile of acute and long-term psychiatric side effects associated with mefloquine.

Methods

Subjects (n = 73) reported to a Danish national register during five consecutive years for mefloquine associated side effects were included. Acute psychiatric side effects were retrospectively assessed using the SCL-90-R and questions based on Present State Examination (PSE). Subjects reporting suspected psychotic states were contacted for a personal PSE interview. Electronic records of psychiatric hospitalizations and diagnoses were cross-checked. Long-term effects were evaluated with SF-36. SCL-90-R and SF-36 data were compared to age- and gender matched controls.

Results

In the SCL-90-R, clinically significant scores for anxiety, phobic anxiety and depression were found in 55%, 51%, and 44% of the mefloquine group. Substantial acute phase psychotic symptoms were found in 15% and were time-limited. Illusions/hallucinations were more frequently observed among women. Cases of hypomania/mania in the acute phase were 5.5%. Significant long-term mental health effects were demonstrated for the SF-36 subscales mental health (MH), role emotional (RE), and vitality (VT) in the mefloquine group compared to matched controls.

Conclusion

The most frequent acute psychiatric problems were anxiety, depression, and psychotic symptoms. Data indicated that subjects experiencing acute mefloquine adverse side effects may develop long-term mental health problems with a decreased sense of global quality of life with lack of energy, nervousness, and depression.

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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