In Canada since 1994, I know of only one advocate to complain about administering the anti-malaria drug treatment, mefloquine, to Canadian troops: John Cummins, Member of Parliament for Delta-South Richmond, British Columbia. His website shows a history of interest and dedicated advocacy for Canadian veterans on the topic of mefloquine, previously marketed under the trade name Lariam. The last question he raised in the House of Commons was printed in the Order Paper as Question 12 (Q-12) in Parliament on February 3, 2004.
Since mefloquine is widely used today by both the United States Department of Defense and the Canadian Department of National Defence (DND) among troops on numerous overseas deployments to such places as Bosnia, Somalia, Rwanda, and Afghanistan, we again need a public voice. How many of you are aware the DND continues to issue mefloquine to Canadian Forces today though they do provide cursory warnings of possible side effects?
In the years that have elapsed since the drug was first used, an unusual and consistent pattern of neurological and psychiatric symptoms has emerged among many troops who have received this drug, including symptoms of chronic insomnia, anxiety, and mood changes. It is difficult to account for the range of diagnoses, including major depression, post traumatic stress disorder, and attempted suicide, frequently occurring among these “mefloquine veterans,” solely by attributing their symptoms to combat experiences. After nearly 20 years of use, many Canadian veterans are concerned that the use of this drug may be contributing to the current epidemic of mental health problems affecting veterans of recent overseas deployments but since it is so difficult for them to qualify for disability benefits, they hesitate to focus on mefloquine as a specific factor in their mental health breakdown.
Interestingly, the 1989 United States FDA approved label for mefloquine clearly warned that “…neurological or psychiatric reactions have been reported during and following the use of [mefloquine]… During prophylactic use, if signs of unexplained anxiety, depression, restlessness or confusion are noticed, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued.”
According to the Report of the Somalia Commission of Inquiry, Canadian troops were directed to take mefloquine weekly by the DND. Despite the warnings on the drug label, there appears to have been few opportunities to identify troops experiencing sides of adverse events, and by the report’s admission, it could not determine whether the DND “…took adequate precautions to ensure that persons with psychiatric disorders did not receive mefloquine, since even in 1992 it was known that mefloquine should not be prescribed to such individuals.”
Recently, I have seen documentation by United States Army researchers studying the early use of mefloquine in Somalia, which found that as many as 18% of troops noted symptoms of anxiety and restlessness, including insomnia and nightmares. Yet, despite credible reports that a large number routinely experienced these symptoms, both Canadian and Unites States troops were not advised to discontinue use of the medication, as directed to by the label.
In the years following the Canadian deployment to Somalia, the popular media featured a number of reports of serious events, including suicide, occurring among troops who had taken mefloquine. Despite these credible reports, the public was repeatedly assured by both the Canadian DND and the United States DoD that no association existed between mefloquine use, suicide, or other serious mental health problems; either in Somalia or during later operations.
The recent experience of the United States is particularly informative in this regard. During a House Armed Services Total Force Subcommittee investigation into the dramatic rise in suicides among United States troops deployed to Iraq, the United States Army Surgeon General, James Peake, testified on February 25, 2004, that “[w]e do not believe that this represents the big causal factor in our suicide rate.” But, is it only by coincidence that after mefloquine was distributed to troops deployed to Iraq, the rate of suicide increased dramatically to 18 per 100,000, from its prior rate of 12 per 100,000? Following these hearings, mefloquine use was subsequently halted in Iraq; but in the years that followed, mefloquine continued to be widely used in United States operations throughout Afghanistan, Asia, and Africa.
Today, the rate of suicide among United States troops is 22 per 100,000 and has been described as an “epidemic.” The Chairman of the United States Joint Chiefs of Staff, Admiral Mullen, recently warned that it will continue to rise. The United States Army Vice Chief of Staff, General Chiarelli, recently admitted, “I don’t totally understand it, but we’re working hard to try and get at it.”
Now it has come to my attention that, earlier this year, the United States Army Medical Research and Material Command quietly awarded $264,000 in funding to a United States Army researcher to investigate suicides associated with mefloquine use. This award follows a quiet move by the United States Defense Department in 2009 to virtually eliminate the use of mefloquine, replacing it in Afghanistan with the equally effective but more expensive medication doxycycline. According to a published report in the Army Times by Kelly Kennedy, a spokesperson for the United States Army Surgeon General’s office, admitted the policy change was motivated by the “inadvertent prescription of mefloquine to soldiers who should not take it.”
Since 2002, United States Army policy has emphasized “critically important” restrictions on the use of mefloquine among soldiers “with active depression or a recent history of depression… or other major psychiatric disorders.” The updated 2009 United States Department of Defense policy even underlined the word “critically.” In his official Subcommittee testimony, Surgeon General Peake assured members of Congress that “…if a Soldier has a history of depression, then an alternative anti-malaria drug is given.” However, in 2008, an internal briefing slide from the United States Army Surgeon General’s office revealed that 7% of recent mefloquine prescriptions were to soldiers with anti-depressant use. One soldier prescribed mefloquine in this manner was subsequently diagnosed with anxiety, attempted suicide, and was later diagnosed with post traumatic stress disorder (PTSD).
A larger study published earlier this year by an United States Army researcher admitted that as many as 34 per 1,000 soldiers were prescribed mefloquine inappropriately, including soldiers who were deployed on antipsychotic medications or who had histories of psychiatric hospitalization. This researcher observed “[t]he possibility that mefloquine, administered inappropriately to those with contraindications, might in some measure be contributory to the current burden of mental health disorders among previously deployed U.S. military personnel, seems apparent from this analysis.”
At face value, these facts reflect an unacknowledged causal association between serious adverse mental health events including suicide, and widespread inappropriate use of mefloquine by the United States DoD and Canadian DND.
As troubling as these facts are, even more troubling are the series of recent published findings of United States Army scientists at the Walter Reed Army Institute of Research, the very laboratory that was involved in the development of mefloquine in the 1970s. Beginning in 2003, researchers studying mefloquine in laboratory animals were describing neurotoxin effects occurring even at low doses, similar to those given to service members. By 2006 these researchers had demonstrated the drug was leading to degeneration of laboratory animal brain stem nuclei, and was causing permanent damage to the central nervous system, suggesting an explanation for how mefloquine might cause long-term mood changes and sleep disorders.
Despite compelling laboratory findings demonstrating neurotoxin effects, and despite evidence that the drug has been widely and inappropriately used, both the Canadian DND and the United States DoD continue to argue that mefloquine is “safe.” Yet, increasingly, it appears both organizations are relying on a biased set of historical studies on which it bases these claims. In fact, the United States DoD has also been delaying performing studies specifically recommended as a condition of mefloquine’s continued use.
Responding to United States congressional concerns about the safety of mefloquine, in 2004, the United States Armed Forces Epidemiological Board, an independent panel of expert health advisors to the Assistant Secretary of Defense for Health Affairs, specifically noted that many gaps existed in the scientific community’s understanding of mefloquine safety. The Board recommended a number of research studies be conducted by the United States DoD to address these questions, including the specific question of suicide associated with mefloquine use. The Board also noted the importance of involving external, civilian researchers to ensure the credibility of the findings.
Admiral Mullen recently observed that the rate of suicide “has gone up dramatically since 2004.” Today – six years after these recommendations were first made – three of the four studies specifically directed by the Board have yet to be performed, including, presciently, “a comprehensive review of DoD suicide data.”
Canada’s DND needs to take urgent action to address the latest research findings on this issue in the following ways:
1. Given the difficulties documented by the United States DoD in ensuring the safe prescribing of mefloquine, the Canadian DND should consider the implementation of a similar policy to dramatically reduce the use of mefloquine. Both the United States and France, for example, now limit the use of mefloquine to those troops with medical contraindications to doxycycline, an equally effective medication with no adverse effects.
2. Given growing international concern over the potential role of mefloquine in mental health problems among deployed armed forces, most recently expressed among troops in Ireland, the Canadian DND should consider convening among its NATO member and partner allies, an international conference of experts to review recent research on the possible neurological and psychiatric sequallae of mefloquine use.
3. To better understand the potential magnitude of any problem, the Canadian DND should be asked to provide updated statistics regarding the number of Canadian troops prescribed mefloquine since the start of the Afghanistan conflict, and an update on any reports of adverse events, including suicides, potentially associated with the use of this drug.
4. Canadian veterans and returning soldiers suffering from adverse effects due to their being issued mefloquine during deployment should be given the same compensation and consideration for specialized treatment as those suffering PTSD, as there also remains a strong chance that neurotoxin effects of mefloquine are linked to some cases of PTSD.
For many years, the United States DoD had confidently asserted the safety and efficacy of this drug; this confidence has resulted in many other nations’ military forces, including Canada’s, to follow suit. Today, this drug has apparently been abandoned by the United States DoD, having been shown to be no better at preventing malaria than existing, safer alternatives. That the reasons for this change have apparently not been widely shared with the Canadian DND raises significant additional questions regarding how to improve and increase transparency of medical information flowing across NATO forces.
Now the question is: how do we get action to safeguard our current armed forces in the field still receiving the anti-malaria treatment, mefloquine? Who will be the voice for the victims of mefloquine use?