On Antimalarials and Afghanistan Shootings

Apr 5, 2012 | Anna Tomasulo | Research & Policy

 

On March 11, American Staff Sgt. Robert Bales allegedly killed 17 Afghan civilians. Amidst the media buzz, reporters, psychiatrists, and even Bales’s lawyer, wonder if certain drugs were linked to this seemingly random act of violence.

Of particular interest to this publication is the possibility that the antimalarial drug, mefloquine (brand name: Lariam) could have been a contributing factor to the shooting.

Currently, the Department of Defense (DoD) is conducting an emergency review of the military’s use of mefloquine. According to Dan Sagalyn for PBS, a Pentagon spokesperson says that the review was ordered weeks before the attack and has “absolutely no connection to the ongoing case or investigation into the actions for which Staff Sgt. Robert Bales has been charged.”

The FDA approved mefloquine as an antimalarial agent in 1989. The drug is used as treatment and prophylaxis for Plasmodium falciparum and Plasmodium vivax species of malaria - which are the malaria species found in Afghanistan. The side effects range from mild events, such as loss of appetite, headaches, sleepiness and unusual dreams to more serious adverse events, such as seizures, anxiety, depression, violent behavior, psychoses, and suicidal thoughts.

In 2002, Roche USA (of Hoffman-Roche, manufacturers of Lariam) made important changes to the drug’s label. Under “contraindications,” the label warned that those with “a recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders” should not be prescribed Lariam for prophylaxis. Further, the drug “may cause psychiatric symptoms in patients” and these symptoms may last long after drug use has stopped. Last, the label notes that if patients experience confusion, depression, or acute anxiety, the drug should be discontinued as these events “may be considered prodromal to a more serious event.”

Several studies have been conducted on adverse events caused by and the neurotoxicity of mefloquine. However, whether or not it has been a direct cause of violence in the military is still unclear.

Mefloquine was a suspect in the 2002 Fort Bragg killings. That summer, four US soldiers, recently returned from tours in Afghanistan, killed their wives. Two of the soldiers then committed suicide. In the months that followed, United Press International followed the case and reported that three of the soldiers had been prescribed mefloquine for malaria prophylaxis while on duty. Statements from the Pentagon and Congress went back and forth: mefloquine was an “unlikely” contributor to the violent behavior according to the Pentagon, while Sen. Chris Dodd, D-Conn and Sen. Dianne Feinstein, D-Calif. relentlessly warned against it.

In 2003 Staff Sgt. Georg-Andreas Pogany suffered a severe panic attack after seeing a mangled body while on duty in Iraq. Consequently, he was accused of having “willfully failed to perform his job” as interrogator, and faced charges of cowardice, an offense punishable by death. His charge was later dropped to dereliction of duty, and in the summer of 2004, he was cleared of all charges because of “medical conditions that require treatment.” According to medical records reportedly reviewed by United Press International, Staff Sgt. Pogany had been diagnosed with “likely Lariam toxicity.”

Politicians have been writing to the DoD about mefloquine use for years. In 2004, the Department of Veterans Affairs sent an information letter to the Under Secretary of Health expressing concern about the possible long-term health effects from mefloquine. The letter states that between 1 in 2,000 and 1 in 13,000 individuals who are using mefloquine may experience serious adverse effects including encephalopathy, psychosis, nightmares, and confusion. The VA also warned that negative side effects may occur for months after the drug is stopped.

In September 2009, the Assistant Secretary of Defense issued a memorandum, which stated that in malaria endemic areas where doxycycline and mefloquine were equally effective in malaria prevention, doxycycline is the drug of choice.

So why is the drug even in use? Mefloquine actually has several advantages when compared to other antimalarial drugs. For starters, mefloquine is taken once a week whereas doxycycline requires a daily dose. For those staying in malaria endemic areas for long durations, a once-a-week pill is often more appealing than a daily dose. Because fewer pills are needed, mefloquine is also considerably less expensive than most antimalarial drugs. Further, drugs affect people in different ways. For some, side effects of doxycycline (increased photosensitivity, nausea, increased yeast infections, and it is not recommended for pregnant women and children under eight) might be more severe than those of mefloquine. Mefloquine is dangerous to those with a history of mood disorders or brain injury, but for people who never experienced either precondition, mefloquine is an acceptable option. 

In the December 2010 issue of the Malaria Journal, researchers from the University of Zurich and the healthcare company Hoffman-Roche published a literature review of mefloquine. According to the authors, the “ideal chemoprophylactic medication should be highly effective, cause few or no adverse events, be indicated for all travelers including pregnant women, nursing women, small children, long-term travelers, should be cheap and easy to use and should be registered globally for this indication.” The CDC recommends five different drugs: a combination of atovaquone and proguanil, chloroquine, doxycycline, mefloquine and primaquine. Currently, none of these drugs meets the requirements.

So, when prescribing a malaria prophylaxis, each individual case must be carefully examined. Family history, physical and emotional health, cost, and destination all play a role in determining the most appropriate prophylaxis.

However, the military is a special population. Differences in the nature of civilian and military travel mandate different courses of malaria prophylaxis. For example, the CDC does not recommend one particular antimalarial drug, rather emphasizes “the goal of individualizing the recommendation for the individual traveler on the basis of past experience, itinerary, possible drug interaction, potential side effects, costs, and medical contraindications such as drug allergies.” For the US Military, on the other hand, “individualizing advice and recommendations for large military deployments is rarely logistically possible or feasible.”

Because of this challenge, the military adopted the 2009 policy to stop using mefloquine when doxycycline was equally effective. However, also noted in the CDC Yellow Book, “there is great variability in practice as to how seriously individual commanders enforce these [malaria prophylaxis] policies…and continued outbreaks of malaria occur in military populations because of poor compliance.”

So, it would seem, the review of the military’s mefloquine use was needed.

Whether or not Bales was taking mefloquine is still unknown; the DoD is not releasing the information due to medical privacy concerns. The DoD has stated, however, that Bales suffered traumatic brain injury in his last tour. Former military psychiatrist Col. Elspeth Ritchie suggests, in Time Magazine’s Battleland, national security trumps medical privacy. According to Ritchie, the “risk-to-benefit ratio is now unacceptably high” and perhaps it is time that the drug is banned completely from military use. Though the conversation around mefloquine is speculative, she writes, the simple fact that the Department of Defense will not offer evidence that the drug was not a cause is concerning. Those who are fighting wars deserve “the best possible care, including documented and sensible protection from malaria.”

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