Lariam (mefloquine) is one of the most widely used malaria drugs in America. Yet it has been linked to grisly crimes, like Army Staff Sgt. Robert Bales' 2012 murder of 16 Afghan civilians, the murders of four wives of Fort Bragg soldiers in 2002 and other extreme violence.
While the FDA beefed up warnings for Lariam last summer, especially about the drug's neurotoxic effects, and users are now given a medication guide and wallet card, Lariam and its generic versions are still the third most prescribed malaria medication. Last year there were 119,000 prescriptions between January and June. Though Lariam is banned among Air Force pilots, until 2011, Lariam was on the increase in the Navy and Marine Corps.
The negative neurotoxic side effects of Lariam can last for "weeks, months, and even years," after someone stops using it, warns the VA. Medical and military authorities say the drug "should not be given to anyone with symptoms of a brain injury, depression or anxiety disorder," reported Army Times—which is, of course, the demographic that encompasses "many troops who have deployed to Iraq or Afghanistan." In addition to Lariam's wide use in the military, the civilian population taking malaria drugs includes Peace Corps and aid workers, business travelers, news media, students, NGO workers, industrial contractors, missionaries and families visiting relatives, often bringing children.
What makes Lariam so deadly? It has the same features that made the street drug PCP/angel dust such an urban legend in the 1970s and 1980s. It can produce extreme panic, paranoia and rage in the user along with out-of-body " dissociative" and dream-like sensations so that a person performing a criminal act often believes someone else is doing it. An example of such dissociative effects was seen in Staff Sgt. Robert Bales' rampage; according to prosecutors at his trial, Bales slipped away from his remote Afghanistan post, Camp Belambay, in a T-shirt, cape and night-vision goggles and no body armor to attack his first victims. He then returned to the base and "woke a fellow soldier, reported what he'd done, and said he was headed out to kill more."
In addition to Bales' 2012 attacks and the 2002 Fort Bragg attacks, Lariam was linked in news reports to extreme side effects in an army staff sergeant in Iraq in 2005 and to the suicide of an Army Reservist in 2008.
Former Army psychiatrist Elspeth Cameron Ritchie, former U.S. Army Major and Preventive Medicine Officer Remington Nevin and Jerald Block with the Portland Veterans Affairs Medical Center agree in a recent paper that Lariam may be behind "seemingly spectacular and impulsive suicides." It can produce "derealization and depersonalization, compulsions toward dangerous objects, and morbid curiosity about death," they write, describing frequent hallucinations "involving religious or morbid themes" and "a sense of the presence of a nearby nondescript figure." The researchers refer to two reports of people jumping out of windows on Lariam under the false belief that their rooms were on fire.
Lariam is one of five malaria drugs listed by the CDC for people who will be exposed to malaria. Other drugs include Malarone, a combination of the drugs atovaquone and Proguanil, Aralen (chloroquine,) primaquine and the antibiotic doxycycline marketed as Vibramycin. None of the drugs are ideal—Malarone can have renal effects and Aralen can have liver, blood and skin effects. Some do not work right away or are ineffective against resistant malaria strains. But the main reason for Lariam's historic popularity is that it is taken weekly, unlike all the other drugs (except chloroquine) which are taken daily. Some travelers also report that Lariam is cheaper than other malaria drugs and say they only experience symptoms like memory loss and vivid nightmares. Still, since awareness of Lariam's dangers, many users are now required to read and sign an informed consent form.
Early Example of Public Funding of Pharma Profits
Lariam was an early example of "technology-transfer" between publicly funded and academic research and Big Pharma, driven by the Bayh-Dole Act of 1980. The Bayh-Dole Act dangled the riches of “industry” before medical institutions just as the former were floundering and the latter was booming, observes Marcia Angell, former editor-in-chief of the New England Journal of Medicine. Turning universities into think tanks for Big Pharma has been so profitable, Northwestern University made $700 million when it sold Lyrica, discovered by one of its chemists, to Pfizer enabling it to build a new research building.
Lariam was developed by the Walter Reed Army Institute of Research (WRAIR) in the 1960s and '70s after a drug-resistant strain of malaria did not respond to medications and sickened troops during the Vietnam War. Though Lariam was developed with our tax dollars, all phase I and phase II clinical trial data were given to Hoffman LaRoche and Smith Kline free of charge in what was the first private public partnership between the U.S. Department of Defense and Big Pharma . You're welcome! It was approved by the FDA in 1989.
Roche, which retained the patent, did well with the government largesse. In 2009, it spent $46.8 billion to buy Genentech (for comparison the entire yearly budget of the National Institutes of Health is $60 billion a year) and its cancer drug, Avastin, makes up to $100,000 per patient per year, despite reports of its limited effectiveness for some cancers for which it is used.
Nor was the testing of Lariam kosher. It was first tested on prisoners and soldiers who are not necessarily able or willing to refuse participation in clinical trials and it was also widely given to Guantanamo detainees. Phase III trials, supposed to be conducted on larger patient groups of up to 3,000 people, were not conducted at all, wrote the Journal of the Royal Society of Medicine in 2007 and "there was no serious attempt prior to licensing to explore the potential drug-drug interactions." In fact, all users "have been involved in a natural experiment to determine the true safety margin," says the journal, because "Consumers have been unwitting recruits to this longitudinal study, rather than informed partners." No wonder Lariam causes adverse effects in as many as 67 percent of users.
As seen with other drugs that have neuropsychiatric effects, like the antidepressant Cymbalta and seizure drug Neurontin, the military, government and Big Pharma blamed the effects on the patients not the drugs. When the wives of four Fort Bragg soldiers were murdered during the summer of 2002—one was stabbed 50 times and set on fire—military investigators blamed "existing marital problems and the stress of separation while soldiers are away on duty," instead of Lariam. Right. Three of the four soldiers also took their own lives.
The military, government and Big Pharma similarly blame the current suicide epidemic among military personnel on factors others than the ubiquitous psychiatric drugs in use—even though 30 percent of the victims never deployed and 60 percent never saw combat. A recent five-year study by Pharma-funded academic, government and military researchers about military suicides does not even consider the drugs given to an estimated fourth of soldiers—almost all of which carry warnings about suicide.
It is also worth noting that the alarming side-effects linked to Lariam which patients, doctors and public health officials reported for at least a decade, were not acknowledged until profits ran out and Lariam became a generic, as has happened with other risky drugs. When sentiment turned against Lariam in 2008, its manufacturer, Hoffmann–La Roche ceased marketing it in the US and now the words "Lariam" and "malaria" draw no search results on its US website. Who, us?
One group that has tried to raise awareness of the dangers of Lariam is Mefloquine (Lariam) Action, created in 1996 when founder, Susan Rose, noticed Peace Corps workers given Lariam were falling ill. Rose soon enlarged the scope of Mefloquine (Lariam) Action to include travelers and military personnel.
"This black box [the strongest FDA warning on drug packaging] officially establishes that mefloquine can cause permanent, brain damage and more. It validates what we have been saying since the beginning," Jeanne Lese, director of Mefloquine (Lariam) Action told me. The problem is far from solved by the black box, says Lese. "The drug continues to be given out at travel clinics all over the U.S. and elsewhere every single day. What's more, it is often prescribed with no hint to the patient about the black box, and no screening for contraindications such as history of previous depression or other neuropsych problems."
Lariam's Checkered Past
The case of the four Fort Bragg soldiers charged with killing their wives during the summer of 2002 is not the only time Lariam has been in the news. There was also the case of Staff Sergeant Andrew Pogany who volunteered to serve in Iraq in 2003 and experienced such panic and PTSD symptoms in the war theater, he was sent back to Fort Carson and charged with “cowardly conduct as a result of fear.” Pogany and his attorney were able to prove that his reaction probably stemmed from Lariam and he received an honorable discharge. But Pogany, understandably, became a vehement advocate for the rights of soldiers with PTSD, especially those who have been given psychoactive drugs that make them worse.
The wife of a 17-year marine veteran I interviewed in 2011 reported a similar story. After being deployed twice to Iraq and once to Afghanistan, her husband developed extreme PTSD. "He went from being loving on the phone, to saying he never wanted to see me and our daughter again," the wife said. "He said not to even bother coming to the airport to meet him, because he would walk right past us." When the couple did reunite, the husband was frail and thin, and "the whites of his eyes were brown," says the wife. The formerly competent drill instructor became increasingly and inexplicably unpredictable, suicidal and violent and was incarcerated in the brig at Camp Lejeune for assault in 2011. I asked the wife to ask him during her visits if he had been given Lariam and she said he said yes.
In the nonﬁction book, Murder in Baker Company: How Four American Soldiers Killed One of Their Own, Lariam is also raised as a possible factor in the brutal death of Army Specialist Richard Davis. When asked about Lariam in the crime in an interview, the author Cilla McCain said, "Although it was never mentioned in court, I think if this same case were to happen today, it would definitely be considered as a defense. These soldiers were overdosing on Lariam in massive amounts because there wasn’t proper oversight. In reality, proper oversight is impossible in a war zone but steps could have been taken to make sure that overdosing didn’t occur. Even without over-dosage the Lariam issue is a volatile one at best and I’m positive we will be hearing more about the damage it has caused for years to come. Some scientists are linking Lariam directly to the historical rise of suicides in the United States."
As a dark cloud grows over Lariam, there is both good and bad news. The good news is in 2013, the Surgeon General's Office of the Army Special Operations Command told commanders and medical workers that soldiers thought to be suffering from PTSD or other psychological problems or even faking mental impairment may actually be Lariam victims. The bad news is a new malaria drug developed at Reed during the same time period as Lariam called tafenoquine is now fast-tracking toward FDA approval. Jeanne Lese and Remington Nevin worry that the new drug has not been adequately tested for the same types of neurotoxic effects seen with Lariam and that it will become Lariam 2.0.
March 27, 2014