Tuesday, July 23, 2013

Antimalarial Drug Linked to Sgt. Robert Bales Massacre - By SUSAN DONALDSON JAMES

U.S. Army Staff Sgt. Robert Bales, who is facing sentencing by a military court for killing 16 civilians on a rampage in Afghanistan last year, might have faced a perfect storm of stress, which included the use of mefloquine hydrochloride, an antimalarial drug given routinely to soldiers in that part of the world.

Mefloquine was developed by the U.S. military and has been used for more than three decades by the government to prevent and to treat malaria among soldiers and Peace Corps workers. But the drug can cause varying neurological side effects 5 to 10 percent of the time, according to Dr. David Sullivan, an infectious disease specialist at Johns Hopkins Malaria Research Institute in Baltimore. The manufacturer also warns against prescribing it to anyone who has suffered a seizure or brain injury, according to the drug label. Bales told a military court he had "no good reason" to kill. Now an adverse-event report from the Food and Drug Administration (FDA) has emerged from March of 2012, written by an unidentified pharmacist, that cites a soldier-patient in the U.S. Army who "developed homicidal behavior and led to homicide killing 17 Afghanis." Bales is not named in that anonymous report, which, if it refers to the same man, erroneously lists 17 dead, rather than 16.

A study of FDA adverse-event reports from 2004 to 2009 published in the journal PLOS One lists mefloquine as a drug that has been associated with violence toward others. Sullivan said the military widely uses antimalarial drugs in Afghanistan, but mefloquine is not the first choice. "Tens of millions of people take it," Sullivan said. "Honestly, you cannot implicate any one thing. To put it all on mefloquine is not fair. [Bales] already has a predisposition because of a traumatic brain injury and he has taken this drug in a stressful situation. You have to put it in context here. … But you can't exclude it." Bales, 39 and the father of two from Washington state, has admitted to the killings after he left of his remote outpost in the southern Afghan province of Kandahar to go on a shooting spree in two nearby villages. The pre-dawn attack left 16 villagers dead and six injured. Nine of those killed were children. There is "not a good reason in the world" for the "horrible things" he did, Bales testified in a military court in June. Bales suffered from head and foot injuries while deployed in Iraq and might have been traumatized by seeing one of his fellow soldiers lose a leg in an explosion hours before the killings, according to testimony. By pleading guilty, he avoided the death penalty, but Bales still faces life imprisonment, with or without parole, at a sentencing trial set for next month.

 According to the adverse-event report from the pharmacist, a man of "unknown demographics" had a history of traumatic brain injury with "no other medications of past drugs. ... this patient was administered mefloquine in direct contradiction to U.S. military rules that mefloquine should not be given to soldiers who had suffered TBI (Traumatic brain injury) due to its propensity to cross blood brain barriers inciting psychotic, homicidal or suicidal behavior." FDA spokesman Stephanie Yao said the report was "authentic." She said anyone could submit such a report, so it is impossible to know who wrote it. "These are voluntary reports," she said. "They are anonymous mainly because of the regulations protecting patient information, so names are not included. "Adverse-event reports are one of the tools we use to monitor the safety of a drug after it is approved," she said. "We encourage people, whether it's a patient or health professional or manufacturer, to submit, so when we see a trend we can look into it in the future to see if there is a safety issue. "In clinical testing, we use smaller populations and once drugs are approved they are used in a much wider population and we must continue to monitor safety." Bales' lawyer, John Henry Browne, told the Seattle Times last week that he has documents indicating his client took mefloquine while in Iraq, but Bales' medical records in Afghanistan were incomplete. "He [Bales] can't help us," Browne said. "He just says he took 'whatever they gave me.'"

Browne did not return a call from ABCNews.com, and the Seattle Times reported that he did not indicate whether he would cite use of mefloquine as a possible contributing factor to Bales' crimes at next month's sentencing. According Time magazine, which first reported on the pharmacist's report, the initial summary eventually made its way to the FDA April 11. Mefloquine, was first developed in the 1970s at the U.S. Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine, the first effective treatment for malaria. It was licensed in 1989 by the FDA for use against chloroquine-resistant malaria. The brand-name drug, Lariam, is manufactured by the Swiss company Hoffmann–La Roche. Side effects for both Lariam and its generic equivalent include severe anxiety, paranoia, hallucinations and depression, according to the manufacturer. The company has not manufactured the drug in the United States since 1998 when generic forms of mefloquine became available. But, according to Sullivan, Lariam is still available and "lingers on the market."

Company senior spokesman Chris Vancheri told ABCNews.com that generic mefloquine "distributed by other companies continues to be approved by the FDA as safe and effective medicines." "The details in the adverse event report are unknown and, therefore, we cannot comment," he said. But according to Time, last year forensic psychiatrist Dr. Remington Nevin testified in Congress on mefloquine's toxic effects that might mimic post-traumatic stress disorder and traumatic brain injury, as well as contribute to suicide and violence. But infectious disease expert Sullivan said mefloquine is largely safe and that he, too, takes a weekly dose of it when traveling and has "never had any side effects." But for those who do, they can experience vivid nightmares, sleep disturbances and difficulty concentrating. "Those are the top side effects and most of the published reports," he said. The military has several drugs in its arsenal for prophylactic (preventive) treatment of malaria, a mosquito-borne disease that causes fever, chills and flu-like illness that, if left untreated, can cause death. An estimated 219 million cases of malaria occurred worldwide and 660,000 people died in 2010, most in Africa, according to the U.S. Centers for Disease Control and Prevention (CDC). "The military uses a combination of drugs," Sullivan said. "It's a good drug, but not for people who have had seizures or brain disorders. Pertinent to the [Bales] case, those with traumatic brain injury are not recommended to take it." Sullivan said the manufacturer also cautions against use of the drug by airline pilots and those who operate heavy machinery. "It's not that they can't, but it does have some side effects like dizziness that occurs in 5 to 10 percent of people taking it, and strange dreams," he said. Typically, two other drugs are used as a "first line" by the military -- tetracycline and tetracycline, taken orally once a day, Sullivan said. But some soldiers are unable to take those drugs because of allergies or intolerance. "Then they go to a couple of other second-line medicines that include mefloquine," he said. "But not for people with seizures or people with traumatic brain injury, that is part of the language on the label for the drug."

Bales was charged with 16 counts of premeditated murder, six counts of attempted murder and seven counts of assault. His only not guilty plea was to a charge of impeding the investigation by destroying a laptop computer. The judge accepted his guilty pleas and scheduled the sentencing for Aug. 19. In a November preliminary hearing, several of his fellow soldiers testified that Bales returned to the base alone just before dawn, covered in blood, and that he made incriminating statements such as, "I thought I was doing the right thing." Some of the blood on him was later matched to at least one of the shooting victims, according to prosecutors. Evidence was also presented that suggested Bales carried out the massacre as revenge for previous attacks on his unit, particularly a roadside bomb attack a few weeks earlier that severely wounded a fellow soldier. Bales did not testify during the two-week hearing, which was to determine whether he would face a court-martial. But some of the surviving villagers did appear via satellite from Afghanistan. Some of his squad mates acknowledged consuming alcohol prior to the attacks, but said Bales did not seem to have been incapacitated. At the June court hearing, the judge also asked Bales about his reported use of steroids to build muscle, which can increase irritability and anger.

As for the mefloquine, malaria specialist Sullivan said, "it was in the mix." But he was hesitant to solely blame the drug on Bales' actions. "Whether it was synergistic or two plus two equals six or two plus two equals ten, without mefloquine, would the two other two factors have been avoided? It's hard to say," he said. "But they are a perfect storm and it did happen and he was on [mefloquine]." He also would not go so far as to say that the drug could trigger violence. "There have been reports," he said."But it's soldiers -- it's not like they are giving it to nuns. Honestly, we would have to see what Carmelite nuns would do [taking the drug.]"

ABC News' Christina Ng contributed to this story.

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