Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review

Tickell-Painter, Maya; Saunders, Rachel; Maayan, Nicola; Lutje, Vittoria; Urdiales, Alberto Mateo; Garner, Paul

doi:10.1016/j.tmaid.2017.10.011

Cited by 9 publications

(12 citation statements)

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“…The findings of our related systematic review which analysed deaths and parasuicides associated with mefloquine prophylaxis, and included case reports, had findings consistent with this ( Tickell‐Painter 2017 ). This systematic review reports that there were no suicides we could reliably attribute to mefloquine prophylaxis, and one para‐suicide with a possible causal association.…”

Section: Discussionmentioning

confidence: 58%

“… we excluded comparisons of mefloquine with primaquine and tafenoquine because these are planned for assessment in another Cochrane Review ( Rodrigo 2016 ); we excluded single‐arm cohort studies because there were sufficient data from comparative studies to reach reasonable conclusions. These studies have been analysed for the very rare outcomes of death or attempted suicide in another systematic review ( Tickell‐Painter 2017 ). …”

Section: Discussionmentioning

confidence: 99%

“…we excluded single‐arm cohort studies because there were sufficient data from comparative studies to reach reasonable conclusions. These studies have been analysed for the very rare outcomes of death or attempted suicide in another systematic review ( Tickell‐Painter 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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Mefloquine for preventing malaria during travel to endemic areas

Tickell-Painter

Maayan²,

Saunders

et al. 2017

Cochrane Database of Systematic Reviews

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BackgroundMefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects.ObjectivesTo summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm); and LILACS. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home) for trials in progress, using 'mefloquine', 'Lariam', and 'malaria' as search terms. The search date was 22 June 2017.Selection criteriaWe included randomized controlled trials (for efficacy and safety) and non-randomized cohort studies (for safety). We compared prophylactic mefloquine with placebo, no treatment, or an alternative recommended antimalarial agent. Our study populations included all adults and children, including pregnant women.Data collection and analysisTwo review authors independently assessed the eligibility and risk of bias of trials, extracted and analysed data. We compared dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). Prespecified adverse outcomes are included in 'Summary of findings' tables, with the best available estimate of the absolute frequency of each outcome in short-term international travellers. We assessed the certainty of the evidence using the GRADE approach.Main resultsWe included 20 RCTs (11,470 participants); 35 cohort studies (198,493 participants); and four large retrospective analyses of health records (800,652 participants). Nine RCTs explicitly excluded participants with a psychiatric history, and 25 cohort studies stated that the choice of antimalarial agent was based on medical history and personal preference. Most RCTs and cohort studies collected data on self-reported or clinician-assessed symptoms, rather than formal medical diagnoses.Mefloquine efficacyOf 12 trials comparing mefloquine and placebo, none were performed in short-term international travellers, and most populations had a degree of immunity to malaria. The percentage of people developing a malaria episode in the control arm varied from 1% to 82% (median 22%) and 0% to 13% in the mefloquine group (median 1%).In four RCTs that directly compared mefloquine, atovaquone-proguanil and doxycycline in non-immune, short-term international travellers, only one clinical case of malaria occurred (4 trials, 1822 participants).Mefloquine safety versus atovaquone-proguanilParticipants receiving mefloquine were more likely to discontinue their medication due to adverse effects than atovaquone-proguanil users (RR 2.86, 95% CI 1.53 to 5.31; 3 RCTs, 1438 participants; high-certainty evidence)....

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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Mefloquine for preventing malaria during travel to endemic areas

Tickell-Painter

Maayan²,

Saunders

et al. 2017

Cochrane Database of Systematic Reviews

Self Cite

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“…body weight 60 ; still some contend that serious side effects from mefloquine are rare. 2,[61][62][63][64] Other than the categories of any antimalarials and other antimalarials in our analysis, only doxycycline and mefloquine plus any other antimalarial showed the greatest associations with PTSD and with PTSD and other anxiety disorders, respectively, before the addition of combat exposure to the models. However, with the inclusion of deployment and combat exposure to regression models, the ORs associated with antimalarial use became attenuated for all health outcomes.…”

Section: Discussionmentioning

confidence: 66%

“…The relationship between antimalarial medications used for chemoprophylaxis and a range of adverse outcomes is documented by case reports and survey studies; however, findings and estimates of risk associated with malaria chemoprophylaxis have been inconsistent and frequently poorly defined. 1,2 The adverse outcomes reported and investigated are most notably dermatological, gastrointestinal (GI), and neuropsychiatric (e.g., includes both central and peripheral nervous system disorders such as headache and dizziness, and psychiatric disorders such as anxiety and depression). [3][4][5] The importance and impact of the possible side effects of antimalarial medication is especially significant for more than 2.7 million U.S. military service members and veterans who served in Southwest Asia and other countries with endemic malaria.…”

Section: Introductionmentioning

confidence: 99%

Associations between Use of Antimalarial Medications and Health among U.S. Veterans of the Wars in Iraq and Afghanistan

Schneiderman

Cypel

Dursa

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Mefloquine (Lariam; Roche Holding AG, Basel, Switzerland) has been linked to acute neuropsychiatric side effects. This is a concern for U.S. veterans who may have used mefloquine during recent Southwest Asia deployments. Using data from the , a population-based study of U.S. veterans who served between 2001 and 2008, we investigated associations between self-reported use of antimalarial medications and overall physical and mental health (MH) using the twelve-item short form, and with other MH outcomes using the post-traumatic stress disorder Checklist-17 and the Patient Health Questionnaire (anxiety, major depression, and self-harm). Multivariable logistic regression was performed to examine associations between health measures and seven antimalarial drug categories: any antimalarial, mefloquine, chloroquine, doxycycline, primaquine, mefloquine plus any other antimalarial, and any other antimalarial or antimalarial combination while adjusting for the effects of deployment and combat exposure. Data from 19,487 veterans showed that although antimalarial use was generally associated with higher odds of negative health outcomes, once deployment and combat exposure were added to the multivariable models, the associations with each of the MH outcomes became attenuated. A positive trend was observed between combat exposure intensity and prevalence of the five MH outcomes. No significant associations were found between mefloquine and MH measures. These data suggest that the poor physical and MH outcomes reported in this study population are largely because of combat deployment exposure.

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Attrition‐Enhanced Deracemization of the Antimalaria Drug Mefloquine

Engwerda¹,

Maassen²,

Tinnemans³

et al. 2018

Angewandte Chemie

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Mefloquine is an important drug for prevention and treatment of malaria. It is commercially available as a racemic mixture, wherein only one enantiomer is active against malaria, while the other one causes severe psychotropic effects. By converting the drug into a compound that crystallizes as a racemizable racemic conglomerate, the deracemization of mefloquine into the desired enantiomer was achieved.

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Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review

Abstract: Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.

Cited by 9 publications

References 44 publications

Mefloquine for preventing malaria during travel to endemic areas

Mefloquine for preventing malaria during travel to endemic areas

Associations between Use of Antimalarial Medications and Health among U.S. Veterans of the Wars in Iraq and Afghanistan

Attrition‐Enhanced Deracemization of the Antimalaria Drug Mefloquine

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