Almost four decades after inventing a potent anti-malarial drug, the U.S. Army has pushed it to the back of its medicine cabinet.
The dramatic about-face follows years of complaints and concerns that mefloquine caused psychiatric and physical side effects even as it was used around the globe as a front-line defense against the mosquito-borne disease that kills about 800,000 people a year.
"Mefloquine is a zombie drug. It's dangerous, and it should have been killed off years ago," said Dr. Remington Nevin, an epidemiologist and Army major who has published research that he said showed the drug can be potentially toxic to the brain. He believes the drop in prescriptions is a tacit acknowledgement of the drug's serious problems.
Over the past three years, the Army slashed by almost 75 percent the amount of mefloquine it prescribes, even as it sent thousands more soldiers to malaria-prone Afghanistan.
The decrease in doses followed two orders from military and Pentagon leaders in 2009. One, from the Army's surgeon general, ordered the branch to limit its use to specific circumstances. Other branches, however, continue to favor mefloquine.
"We are constantly looking to ensure we are taking care of (soldiers) the best we can," said Army Col. Carol Labadie, the service's pharmacy program manager. "If that means changing from one drug to another because now this original drug has shown to be potentially harmful ... it is in our interests to make that change."
Army researchers started developing mefloquine toward the end of the Vietnam War and began using it widely after it was licensed by Roche Pharmaceuticals under the brand name Lariam in the early 1990s.
It gained support among the fighting forces because it works in areas where mosquitoes developed resistance to an earlier treatment, chloroquine, and requires just one tablet a week, not the daily dose needed with other medications.
For years, the Army downplayed veterans' criticism of the drug and insisted its protection against malaria easily outweighed the small risks.
Some users complained the pill caused varying degrees of psychiatric symptoms ranging from nightmares, depression and paranoia to auditory hallucinations and complete mental breakdowns. Army literature says such symptoms occur at a rate of between one per 2,000-13,000 people. Critics, including Nevin, contend the number is far higher.
Family members have even blamed the drug on their loved ones' suicides.
Retired Navy Capt. Gary Foster said he cut his career short in part because of the effects of taking mefloquine in 2008 and 2009.
"I began to suffer short term memory loss, not able to recall what I had done earlier," he wrote in an email. "I also had more bouts of anxiety, and I cannot for the life of me tell you why."
In February 2009, Army Surgeon General Eric Schoomaker sent a policy memo to doctors saying it should be used only if soldiers could not tolerate doxycycline, a general antibiotic effective at preventing malaria.
In September 2009, Ellen P. Embrey, who at the time was deputy assistant secretary of defense overseeing health affairs, sent a letter similar to Schoomaker's. This time, it was directed across all military branches.
A small but vocal group of anti-mefloquine campaigners seized on the memos as vindication.
"I was stunned," said retired Navy commander Bill Manofsky, who said he sustained permanent damage to his sense of balance after taking Lariam in Kuwait in 2002 and has been a persistent critic of the drug.
"It's like you scream into a hurricane until you are hoarse," he said. "We knew we were right."
Roche says it stopped selling Lariam in the U.S. in 2008 because of the availability of generics and alternative therapies.
Roche spokesman Christopher Vancheri said in an email he could not comment on the military's stance on mefloquine, but noted that the drug continues to be available in over 50 countries.
In 2008, the Army dispensed 8,574 courses of the drug. In 2010, it fell to 2,054. At the same time, the Army increased fivefold the number of doxycycline prescriptions _ to more than 80,000 _ reflecting the increasing number of soldiers deployed to Afghanistan.
Spending followed a similar pattern, with the Pentagon buying almost $1.8 million of mefloquine in 2009, enough for about 10,000 yearlong courses. The amount dropped to $1.5 million last year. So far this year, the military has only spent about $50,000.
It's not clear how many of the tablets have been dispensed.
The Navy and Marine Corps have actually slightly increased their mefloquine prescriptions over the past three years, from about 1,200 in 2008 to nearly 2,000 last year. Numbers could be higher still because prescriptions filled overseas are frequently not counted.
The Air Force, which has long banned its pilots from using the drug, has been decreasing its usage over the past two years.
Capt. Christopher Clagett, who directs the Navy's Department of Preventive Medicine, said his service's view is mefloquine remains one of his best tools to prevent malaria. He said it is much cheaper than the most effective drug, Malarone, and can often work better than doxycycline.
"It would be imprudent and would place our personnel at the far greater risk of malaria to abandon an effective anti-malarial due to unsubstantiated allegations of chronic effects," Clagett wrote in an email, "than to continue the judicious and selective use of an imperfect, but nevertheless effective and valuable medication."
In August, Sen. Dianne Feinstein, D-Calif., wrote to the secretaries of Defense and Veterans Affairs, urging them to strengthen safeguards for the use of the drug. The VA last month stripped mefloquine from the advice section on its website while it reviews recent research into the drug's side effects.
Nevin, the Army doctor, has riled superiors with public attacks on mefloquine, calling it "probably the worst-suited drug for the military." He noted that its side effects can closely mirror symptoms of stress disorders related to combat, making diagnosis of neurological problems difficult.
"It is a story of the military bureaucracy gradually and reluctantly coming to terms with a tragic, possibly catastrophic, decades-long series of errors and missteps," Nevin said.
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