1921
Volume 96, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

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.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.16-0390
2017-01-11
2018-01-19
Loading full text...

Full text loading...

/deliver/fulltext/14761645/96/1/159.html?itemId=/content/journals/10.4269/ajtmh.16-0390&mimeType=html&fmt=ahah

References

  1. Kitchen LW, Vaughn DW, Skillman DR, , 2006. Role of US military research programs in the development of US Food and Drug Administration–approved antimalarial drugs. Clin Infect Dis 43: 6771.[Crossref]
  2. U.S. Food and Drug Administration, 2013. FDA Approves Label Changes for Antimalarial Drug Mefloquine Hydrochloride due to Risk of Serious Psychiatric and Nerve Side Effects. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM362232.pdf. Accessed April 7, 2016.
  3. Office of the Assistant Secretary of Defense (Health Affairs), 2009. Memorandum: Policy Memorandum on the Use of Mefloquine (Lariam) in Malaria Prophylaxis. Available at: http://www.health.mil/∼/media/MHS/Policy%20Files/Import/09-017.ashx. Accessed April 7, 2016.
  4. Office of the Assistant Secretary of Defense (Health Affairs), 2013. Memorandum: Guidance on Medications for Prophylaxis of Malaria. HA Policy 13-002. Available at: http://www.health.mil/∼/media/MHS/Policy%20Files/Import/13-002.ashx. Accessed April 7, 2016.
  5. Wells TS, Smith TC, Smith B, Wang LZ, Hansen CJ, Reed RJ, Goldfinger WE, Corbell TE, Spooner CN, Ryan MA, , 2006. Mefloquine use and hospitalizations among US service members, 2002–2004. Am J Trop Med Hyg 74: 744749.
  6. Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, Herold M, Krebs B, Veit O, Allwinn R, Steffen R, , 2003. Tolerability of malaria chemoprophylaxis in non-immune travelers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study. BMJ 327: 1078.[Crossref]
  7. Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Rhein HG, , 2010. The position of mefloquine as a 21st century malaria chemoprophylaxis. Malar J 9: 357371.[Crossref]
  8. Schneider C, Adamcova M, Jick SS, Schlagenhauf P, Miller MK, Rhein HG, Meier CR, , 2013. Antimalarial chemoprophylaxis and the risk of neuropsychiatric disorders. Travel Med Infect Dis 11: 7180.[Crossref]
  9. Overbosch D, Schilthuis H, Bienzle U, Behrens RH, Kain KC, Clarke PD, Toovey S, Knobloch J, Nothdurft HD, Shaw D, Roskell NS, Chulay JD, Malarone International Study Team; , 2001. Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study. Clin Infect Dis 33: 10151021.[Crossref]
  10. van Riemsdijk MM, Sturkenboom MC, Pepplinkhuizen L, Stricker BH, , 2005. Mefloquine increases the risk of serious psychiatric events during travel abroad: a nationwide case-control study in The Netherlands. J Clin Psychiatry 66: 199204.[Crossref]
  11. van Riemsdijk MM, Sturkenboom MC, Ditters JM, Ligthelm RJ, Overbosch D, Stricker BH, , 2002. Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: a focus on neuropsychiatric adverse events. Clin Pharmacol Ther 72: 294301.[Crossref]
  12. Jacquerioz FA, Croft AM, , 2009. Drugs for preventing malaria in travellers. Cochrane Database Syst Rev 4: CD006491.
  13. Barrett PJ, Emmins PD, Clarke PD, Bradley DJ, , 1996. Comparison of adverse events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travellers. BMJ 313: 525528.[Crossref]
  14. Korhonen C, Peterson K, Bruder C, Jung P, , 2007. Self-reported adverse events associated with antimalarial chemoprophylaxis in peace corps volunteers. Am J Prev Med 33: 194199.[Crossref]
  15. Fujii T, Kaku K, Jelinek T, Kimura M, , 2007. Malaria and mefloquine prophylaxis use among Japan Ground Self-Defense Force personnel deployed in east Timor. J Travel Med 14: 226232.[Crossref]
  16. Naing C, Aung K, Ahmed SI, Mak JW, , 2012. Signal detection to identify serious adverse events (neuropsychiatric events) in travelers taking mefloquine for chemoprophylaxis of malaria. Drug Healthc Patient Saf 4: 8792.[Crossref]
  17. Jaspers CA, Hopperus Buma AP, van Thiel PP, van Hulst RA, Kager PA, , 1996. Tolerance of mefloquine chemoprophylaxis in Dutch military personnel. Am J Trop Med Hyg 55: 230234.
  18. Rubertone MV, Brundage JF, , 2002. The Defense Medical Surveillance System and the Department of Defense serum repository: glimpses of the future of public health surveillance. Am J Public Health 92: 19001904.[Crossref]
  19. Armed Forces Health Surveillance Center (AFHSC), 2012. Mental disorders and mental health problems, active component, U.S. Armed Forces, 2000–2011. MSMR 19: 1117.
  20. Armed Forces Health Surveillance Center, 2010. Insomnia, active component, U.S. Armed Forces, January 2000–December 2009. MSMR 17: 1215.
  21. Armed Forces Health Surveillance Center, 2012. Case Definitions for Data Analysis and Health Reports: Section 12, Mental Health. Available at: https://www.afhsc.mil/documents/pubs/documents/CaseDefs/Web_12_MENTAL%20HEALTH_DEC15.pdf. Accessed April 7, 2016.
  22. Department of Defense Deployment Health Clinical Center, 2006. Enhanced Post-Deployment Health Assessment (PDHA) Process (DD Form 2796). Available at: http://www.dtic.mil/whs/directives/forms/eforms/dd2796.pdf. Accessed April 7, 2016.
  23. Zelen M, , 1972. Exact Significance Tests for Contingency Tables Embedded in a 2nd Classification. The Sixth Berkeley Symposium on Mathematical Statistics and Probability. Berkeley, CA: University of California Press, 737757.
  24. Good P, , 2005. Permutation, Parametric, and Bootstrap Tests of Hypotheses. New York, NY: Springer-Verlag.
  25. Ernst MD, , 2004. Permutation methods: a basis for exact inference. Stat Sci 19: 676685.[Crossref]
  26. DiCiccio TJEB, , 1996. Bootstrap confidence intervals. Stat Sci 11: 189228.[Crossref]
  27. Rizzo RL, , 2007. Statistical Computing with R. Boca Raton, FL: Chapman and Hall/CRC.
  28. Efron B, , 1979. Bootstrap methods: another look at the jackknife. Ann Stat 7: 126.[Crossref]
  29. Roche USA, 2004. Lariam Brand of Mefloquine Hydrochloride Tablets (Package insert). Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf. Accessed April 7, 2016.
  30. Kitchener SJ, Nasveld PE, Gregory RM, Edstein MD, , 2005. Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in east Timor. Med J Aust 182: 168171.
  31. van Riemsdijk MM, Ditters JM, Sturkenboom MC, Tulen JH, Ligthelm RJ, Overbosch D, Strickler BH, , 2002. Neuropsychiatric events during prophylactic use of mefloquine before travelling. Eur J Clin Pharmacol 58: 441445.[Crossref]
  32. Ringqvist A, Bech P, Glenthoj B, Petersen E, , 2014. Acute and long-term psychiatric side effects of mefloquine: a follow-up on Danish adverse event reports. Travel Med Infect Dis 13: 8088.[Crossref]
  33. Peterson AL, Seegmiller RA, Schindler LS, , 2011. Severe neuropsychiatric reaction in a deployed military member after prophylactic mefloquine. Case Rep Psychiatry 2011: 350417.
  34. van Riemsdijk MM, Sturkenboom MC, Ditters JM, Tulen JH, Ligthelm RJ, Overbosch D, Strickler BH, , 2004. Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine. Br J Clin Pharmacol 57: 506512.[Crossref]
  35. Nevin RL, Pietrusiak PP, Caci JB, , 2008. Prevalence of contraindications to mefloquine use among USA military personnel deployed to Afghanistan. Malar J 7: 3034.[Crossref]
  36. Hill DR, , 1991. Pre-travel health, immunization status, and demographics of travel to the developing world for individuals visiting a travel medicine service. Am J Trop Med Hyg 45: 263270.
  37. Bloechliger M, Schlagenhauf P, Toovey S, Schnetzler G, Tatt I, Tomianovic D, Jick SS, Meier CR, , 2014. Malaria chemoprophylaxis regimens: a descriptive drug utilization study. Travel Med Infect Dis 12: 718725.[Crossref]
  38. Brisson M, Brisson P, , 2012. Compliance with antimalaria chemoprophylaxis in a combat zone. Am J Trop Med Hyg 86: 587590.[Crossref]
  39. Armed Forces Health Surveillance Center, 2014. Surveillance snapshot: self-reported malaria prophylaxis compliance among U.S. service members with diagnosed malaria, 2008–2013. MSMR 21: 15.
  40. Phillips MA, Kass RB, , 1996. User acceptability patterns for mefloquine and doxycycline malaria chemoprophylaxis. J Travel Med 3: 4045.[Crossref]
  41. Saunders DL, Garges E, Manning JE, Bennett K, Schaffer S, Kosmowski AJ, Magill AJ, , 2015. Safety, tolerability, and compliance with long-term antimalarial chemoprophylaxis in American soldiers in Afghanistan. Am J Trop Med Hyg 93: 584590.[Crossref]
  42. Sonmez A, Harlak A, Kilic S, Polat Z, Hayat L, Keskin O, Dogru T, Yilmaz MI, Acikel CH, Kocar IH, , 2005. The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan. J Infect 51: 253258.[Crossref]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.16-0390
Loading
/content/journals/10.4269/ajtmh.16-0390
Loading

Data & Media loading...

  • Received : 16 May 2016
  • Accepted : 09 Sep 2016

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error