Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: A focus on neuropsychiatric adverse events*

Riemsdijk, Melanie M. van; Sturkenboom, Miriam; Ditters, J.; Ligthelm, Robert J.; Overbosch, David; Stricker, Bruno H. Ch.

doi:10.1067/mcp.2002.127113

Cited by 42 publications

(29 citation statements)

References 14 publications

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“…15,17,30 Contrary to our findings, other studies have reported an association between NPOs and mefloquine. 6,10,11,13,[31][32][33] The study by Schlagenhauf and others was a randomized, double-blinded study among travelers and found mefloquine to have the highest proportion of moderate to severe NPOs compared with chloroquine/proguanil, doxycycline, and A/P. 6 However, this study had small numbers and the outcomes were defined by a subjective questionnaire as opposed to medical diagnoses of the outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] Studies evaluating the occurrence of neuropsychiatric outcomes (NPOs) after mefloquine use report mixed results, but a large proportion of these studies found an association between mefloquine and NPOs. [7][8][9][10][11][12][13][14][15][16][17] Due to the extensive use of mefloquine for malaria prevention among service members before 2009 and its continued, limited use, after that point, the need to evaluate adverse events in service members who took the drug is evident. Therefore, a retrospective population-based cohort study was conducted among service members.…”

Section: Introductionmentioning

confidence: 99%

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Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

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Rohrbeck

et al. 2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Mefloquine was widely prescribed to U.S. military service members until 2009 when use was limited to personnel with contraindications to doxycycline and no contraindications to mefloquine. The need to estimate the occurrence of neuropsychiatric outcomes (NPOs) in service members prescribed mefloquine warranted a comprehensive evaluation of this issue. Active component service members filling a prescription for mefloquine, doxycycline, or atovaquone/proguanil (A/P) between January 1, 2008 and June 30, 2013, were included in the analysis. The risk of developing incident NPOs and the risk of subsequent NPOs among subjects with a history of the condition were assessed. A total of 367,840 individuals were evaluated (36,538 received mefloquine, 318,421 received doxycycline, and 12,881 received A/P). Among deployed individuals prescribed mefloquine, an increased risk of incident anxiety was seen when compared with doxycycline recipients (incidence rate ratio [IRR] = 1.12 [1.01-1.24]). Among nondeployed mefloquine recipients, an increased risk of posttraumatic stress disorder (PTSD) was seen when compared with A/P recipients (IRR = 1.83 [1. 07-3.14]). An increased risk of tinnitus was seen for both deployed and nondeployed mefloquine recipients compared with A/P recipients (IRR = 1.81 [1.18-2.79]), 1.51 (1.13-2.03), respectively). Six percent of the mefloquine cohort had an NPO in the year before receiving mefloquine. When comparing individuals with a prior neuropsychiatric history to those without, the ratio of relative risks for adjustment disorder, anxiety, insomnia, and PTSD were higher (not statistically significant) for mefloquine compared with doxycycline. These findings emphasize the continued need for physicians prescribing mefloquine to conduct contraindication screening.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

Eick-Cost

Rohrbeck

et al. 2017

The American Society of Tropical Medicine and Hygiene

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“…There was a further potential source of bias in that, except for two trials, 20,26 all the trials in this review were funded wholly or in part by drug companies. The exact nature of this funding was not always clear or available.…”

Section: 20mentioning

confidence: 99%

“…17,20,21 interventions Atovaquone-proguanil was compared against doxycycline in one trial, 27 and against mefloquine in three trials. 24,26,27 Doxycycline was compared against mefloquine in three trials. 17,21,27 Four trials compared any of the above drugs against chloroquine-proguanil.…”

Section: Participantsmentioning

confidence: 99%

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Drugs to Prevent Malaria in Travellers: A Systematic Review of Randomized Controlled Trials

Croft¹,

Jacquérioz²,

Jones³

2010

Human Parasitic Diseases

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Background: Malaria infects 10,000 to 30,000 international travellers each year. It can be prevented through anti-mosquito measures and drug prophylaxis. We did a systematic review to assess the effects of currently used antimalaria drugs, given as prophylaxis to nonimmune adult and child travellers to regions with chloroquine-resistant Plasmodium falciparum malaria. Methods: We included randomized and quasi-randomized controlled trials of any antimalaria drug regimen currently used by international travellers, compared against any other currently used regimen. In August 2009 we searched MEDLINE, EMBASE, LILACS, BIOSIS, mRCT, and the Cochrane Register of Controlled Trials (CENTRAL), without time restrictions. We searched reference lists, conference proceedings and one specialist journal, and contacted researchers and drug companies. We summarized the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials. Results: Eight trials (4240 participants) were included. One-quarter of trial participants were soldiers. Duration of exposure to malaria ranged from 15 days to 13 weeks. All trials reported common adverse events from antimalaria drugs. Atovaquone-proguanil users and doxycycline users had similar frequencies of reported adverse effects. Atovaquone-proguanil users had fewer reports of any adverse effect than mefloquine users (RR 0.72, 95% CI 0.6 to 0.85), also fewer gastrointestinal adverse effects (RR 0.54, 95% CI 0.42 to 0.7), and fewer neuropsychiatric adverse effects (RR 0.49, 95% CI 0.38 to 0.63). Chloroquine-proguanil users had more reports of any adverse effect than users of other drugs (RR 0.84, 95% CI 0.73 to 0.96), also more gastrointestinal adverse effects (RR 0.71, 95% CI 0.6 to 0.85). We found no evidence on primaquine in travellers. Conclusions: There is limited evidence on which currently available drug is most effective in preventing malaria. Atovaquone-proguanil and doxycycline are the best tolerated regimens. Doxycycline monohydrate appears exceptionally useful due to its good safety profile, low cost and protective efficacy against many travel-related infections, besides malaria. Mefloquine is associated with adverse neuropsychiatric outcomes. Chloroquine-proguanil is associated with adverse gastrointestinal outcomes. There is no evidence to support the use of primaquine as prophylaxis in travellers.

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Controversies and Misconceptions in Malaria Chemoprophylaxis for Travelers

Chen¹,

Wilson²,

Schlagenhauf³

2007

JAMA

110

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Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: A focus on neuropsychiatric adverse events*

Abstract: Prophylactic use of mefloquine was associated with significantly higher scores on scales for depression, anger, and fatigue and lower scores for vigor than prophylactic use of atovaquone plus chloroguanide.

Cited by 42 publications

References 14 publications

Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

Neuropsychiatric Outcomes After Mefloquine Exposure Among U.S. Military Service Members

Drugs to Prevent Malaria in Travellers: A Systematic Review of Randomized Controlled Trials

Controversies and Misconceptions in Malaria Chemoprophylaxis for Travelers

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