A scientific panel plans to publish next year the results of year-long study of anti-malarial drugs used by U.S. troops and other federal workers, a review greatly anticipated by former service members and Peace Corps volunteers who say their debilitating mental and physical health symptoms were caused by mefloquine, a once-a-week malaria preventive issued to thousands who served overseas.
At the request of the Department of Veterans Affairs, National Academies of Sciences, Engineering and Medicine researchers are examining existing scientific literature to determine whether anti-malaria drugs, including mefloquine, also known as Lariam, cause brain damage, neurological conditions or psychiatric disorders.
During a meeting of the panel earlier this year, military veterans and Peace Corps volunteers told members how their lives were shattered by mefloquine — a prescription they were ordered to take but frequently wasn’t documented in their health records.
Marine Col. Timothy Dunn, who retired in 2018 after nearly 30 years of service, said he began experiencing vivid dreams, insomnia, anxiety, depression and “brain fog” as soon as he began taking mefloquine on deployment in 2006.
Since then, his symptoms have worsened, he said, to include vertigo, ringing in his ears and loss of balance.
“You have to do something to look at this closely and make a fair and just determination,” Dunn told the panel. “There are many more than I who have had this problem.”
Sarah Thompson, a Peace Corps volunteer in Burkina Faso from 2010 to 2012, said she was issued a large dose of mefloquine on arriving in the country and then took it once a week for two years.
She developed psychiatric symptoms, which she reported to her medical advisers, and later, disabling dizziness and vertigo. It wasn’t until she returned home, however, that she learned of mefloquine’s potential side effects because she never received the original packaging or instructions.
“It’s been over six years since my return from West Africa and I continue to experience the side effects from this drug,” Thompson told the panel March 27. “I know countless other volunteers who continue to struggle on a daily basis and who are on disability which can be confidently attributed to this drug.”
U.S. service members routinely take malaria prophylaxis medications when deploying to countries where malaria is endemic, such as Afghanistan, Djibouti and throughout Africa. But anti-malarials also were prescribed in places where the mosquito-borne disease is not prevalent, such as Iraq, which has been malaria-free since 2008.
The National Academies group is looking at all available studies and literature on FDA-approved anti-malarials used by the Department of Defense, giving special attention to "long-term neurological effects, psychiatric effects and the potential development of post-traumatic stress disorder.”
If a causal relationship can be determined between taking the medications and disabling health effects, it could speed the process for affected veterans to receive health benefits and disability compensation from VA.
Veterans can currently file a disability claim with VA for anti-malarial poisoning, but each case is decided individually. To prove their case, the medication must be documented in their medical record and they must demonstrate that their symptoms began when they started taking the drugs.
Mike Richman, a public affairs specialist in the VA’s Office of Public and Intergovernmental affairs, pointed out that there is no formal diagnosis for “mefloquine poisoning” or “mefloquine toxicity,” and that there is a diagnosis for poisoning by anti-malarials, but it is “time-limited,” generally intended for acute reactions.
Richman added that serious side effects of mefloquine, like seizures and psychotic reactions, are “very rare, occurring roughly 1 of 11,000 cases following preventive use,” and that while “some people have had reactions to mefloquine and other medications, “there are many causes for issues that could be attributed to this.”
In June, VA researchers, led by VA’s Director of Post-Deployment Health Services Aaron Schneiderman, found that “while anti-malarial use was generally associated with higher odds of negative health outcomes … no significant associations were found between mefloquine” and mental disorders when variables such as combat exposure and deployment were considered.
“No significant associations were found between mefloquine and mental health measures. These data suggest that the poor physical and mental health outcomes reported in this study population are largely because of combat deployment exposure,” they wrote in the American Journal of Tropical Medicine and Hygiene.
Dr. Remington Nevin, a former Army preventive medicine officer, researcher and executive director of The Quinism Foundation, a group dedicated to supporting research on quinoline drugs, including mefloquine, took issue with the VA’s conclusion, penning his own response to the journal.
He suggested that physicians treating veterans who display symptoms of post-traumatic stress disorder — symptoms similar to adverse reactions seen in mefloquine users — ask their patients if they began experiencing anxiety or nightmares preceding combat but after taking mefloquine.
“The authors’ findings from unadjusted analysis underscore concerns that chronic adverse mental health effects from mefloquine may mimic those of combat deployment-related mental health conditions and thus contribute to misdiagnosis,” he wrote in February. “To assess causation … clinicians evaluating veterans must take a careful mefloquine history, identifying when the symptoms first occurred in relation to drug use and to plausible traumatic events.”
Nevin also noted that the current lack of a specific mefloquine poisoning diagnosis is a reflection that the Defense Department and VA have never formally acknowledged the side effects of mefloquine.
“[They] have never acknowledged, much less trained their clinical workforce to recognize that certain signs and symptoms that can mimic those of PTSD or TBI, and several other neurologic and psychiatric disorders, are in fact caused by nothing more than the lasting effects of the drug,” Nevin told Military Times.
Mefloquine was developed in the 1970s at the Walter Reed Army Institute of Research, which turned it over to the pharmaceutical company F. Hoffmann-LaRoche to manufacture under the brand name Lariam.
The FDA approved its use for treating and preventing malaria in 1989. But in the 1990s, stories began to surface regarding some serious side effects among patients who took mefloquine, including vivid dreams and nightmares, hallucinations, mania, seizures, depression, suicidal thoughts, suicide and homicide.
Mefloquine psychosis was raised as an explanation in 2002 at Fort Bragg, North Carolina, when, during a six-week period, three U.S. Army Special Operations Command soldiers who had recently returned from Aghanistan, murdered their wives. All three later died by suicide.
Investigation into the deaths concluded that a history of marital problems and deployment stress likely contributed to the killings, but concern over the medication continued. In 2009, the U.S. Army issued a policy listing it as a last-choice malaria preventive and said it should not be used in personnel with a history of head injury, neurological disorders or mental health condition.
In January 2012, the assistant secretary of defense for health ordered a full-scale review of mefloquine prescription policies, and in 2013, the FDA placed its strongest warning on mefloquine, saying the drug can cause ongoing or permanent neurological and psychiatric conditions, including dizziness, loss of balance, tinnitus, anxiety, depression, paranoia and hallucinations, even after discontinuing use.
Case studies also have shown that neurological damage related to mefloquine use has symptoms similar to PTSD. In 2016, an Army physician published a study of a 32-year-old service member who had been diagnosed with PTSD but also had cognitive issues and vertigo. His physicians linked his symptoms to mefloquine after other treatments failed.
From 1989 through September 2019, the FDA received 3,990 reports of adverse effects associated with mefloquine, 3,672 of which were labeled as serious, with more than half being psychiatric conditions, and 172 deaths.
The FDA’s reporting system only shows that an undesirable symptom or consequence occurred in a patient who took mefloquine and does not indicate the drug caused the negative outcome. It simply denotes that the medication had been taken at some point before an adverse event occurred.
Still, according to the FDA’s Adverse Event Reporting System, some of the events that followed mefloquine use included seizures, mania, depression, suicidal thoughts, hallucinations, suicide attempts, 23 suicides and six cases of homicide, including a chilling report filed April 11, 2012, by manufacturer Roche noting the company had been notified by an unnamed health provider that the drug was implicated in the killings of Afghan villagers — the massacre promulgated by Staff Sgt. Robert Bales on March 11, 2012.
Bales is now seeking a new trial in civilian court, with his attorneys charging that mefloquine use was not introduced at the original trial and that he would not have been of sound mind as a result of taking mefloquine to agree to a strategy that excluded it from his defense or in filing his guilty plea.
According to VA, 209 veterans have been referred or self-referred to the department’s War Related Illness and Injury Study Center seeking assessments for mefloquine-related issues. Of those, 94 completed an intake package and 41 responded to letters of invitation from VA for full assessments and were studied at the WRIISC.
Richman cautioned, however, that the 41 veterans are not “representative of veterans at large or veterans seen in VA primary care.”
The 41 also “were not representative of the 209 who initially reported mefloquine-related concerns and not all had a mefloquine-related issue,” said Richman.
“Veterans with conditions they believe are related to mefloquine may be seen and evaluated and veterans entitled to full VA health coverage can receive health care for all of their health conditions,” he said. “Veterans who believe they are experiencing mefloquine-related issues should relay their health concerns about to their primary physician.”
In December, a former Navy SEAL filed a lawsuit against Roche alleging that the drug left him permanently disabled. The suit alleges that the pharmaceutical company knew that the drug caused serious side effects and failed to warn patients.
The case is currently winding through the legal process, with Roche claiming that the court where the case resides, U.S. District Court, Northern District of California, does not have jurisdiction over the international pharmaceutical corporation, which stopped selling Lariam in the U.S. in 2009.
A judge has ruled the case may proceed in state court.
Internationally, more than 900 Canadian veterans have filed lawsuits against the Canadian government and Department of National Defence over mefloquine, charging that leadership “willfully ignored and concealed the risks” of the medication.
In Ireland, soldiers also have taken legal action against the Irish Minister for Defence, which has moved to settle some of the cases.
In Australia, a government study found that side effects from mefloquine were rare, but the Australian Department of Veterans Affairs has committed more than $2 million in Australian dollars to provide comprehensive health assessments to veterans who believe they have been affected by antimalarial medications.