The Quinism Foundation Renews Its Call for Congress to Fund Veteran-Focused Research into Mefloquine Neurotoxicity and Chronic Quinoline Encephalopathy

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The National Academies of Sciences, Engineering and Medicine Finds Research is Needed into the Chronic Adverse Effects of Mefloquine and Related Quinoline Antimalarial Drugs

The Quinism Foundation is again calling on Congress to fund critical veteran-focused research into the chronic adverse neurological and psychiatric effects of mefloquine and related neurotoxic quinoline antimalarial drugs, nearly a year following release of a report by an ad hoc committee of the National Academies of Sciences, Engineering, and Medicine (NASEM) [1]. The NASEM committee was charged by the U.S. Department of Veterans Affairs with looking at “long-term health effects” of antimalarial medication, with “special attention” “to possible long-term neurologic effects," and "long-term psychiatric effects."

On February 25, 2020, the NASEM committee publicly released its final report. It observed a “disconnect between the level of concern raised–millions of people have used the drugs, and there are many known concurrent events and case reports of adverse events–and the systematic research that has been conducted, particularly in areas such as the use of mefloquine and persistent neurological or psychiatric outcomes.” The committee found “there is a sharp contrast between the abundant amount of literature pertaining to concurrent adverse events that are experienced while a drug is being used or shortly following its cessation and the dearth of information, especially high-quality information, pertaining to adverse experiences after the use of that drug has ended." [1]

“To address the critical research needs identified by NASEM, Congress should establish mefloquine neurotoxicity / chronic quinoline encephalopathy (quinism) as a perennial research topic under the Peer-Reviewed Medical Research Program (PRMRP) within the Department of Defense (DoD) Congressionally Directed Medical Research Program (CDMRP)," said Remington Nevin, MD, MPH, DrPH, executive director of The Quinism Foundation.

The Quinism Foundation identified five focus areas for future research, including conducting high-quality epidemiological studies related to persistent and latent health effects of antimalarial quinolines, particularly mefloquine.

"In a chapter titled 'Improving the Quality of Research on the Long-Term Health Effects of Antimalarial Drugs,'" Dr. Nevin said, "the committee noted the importance of epidemiological study designs that 'allow for the discovery of symptoms or diagnoses that covary. For example, if certain symptoms or diagnoses occur together in the same patients, there may be reason to consider a syndrome of "neuropsychiatric" symptoms that co-occur, rather than looking individually at separate neurologic or psychiatric experiences.' The committee also noted that a 'challenge when studying adverse events of drugs is that the occurrence of adverse events [e.g. prodromal psychiatric symptoms such as nightmares, insomnia, anxiety, depression, restlessness, and confusion during use of mefloquine (i.e., symptomatic exposure)] may cause an individual to decide to modify the dose, or even stop the drug completely, without consulting a health professional.'"

"This focus area should aim to fund epidemiological studies meeting the NASEM Committee’s criteria relative to persistent and latent health effects of antimalarial quinolines, particularly mefloquine – to include valid assessment of symptomatic quinoline exposure and particularly symptomatic mefloquine exposure, and subsequent covarying symptoms or diagnoses consistent with the described presentation of chronic quinoline encephalopathy," Dr. Nevin said.

Other focus areas identified in the white paper include defining persistent or latent central nervous system effects of antimalarial quinoline neurotoxicity, defining adverse neurophysiological effects of antimalarial quinolines, disentangling comorbid neuropsychiatric diagnoses confounded by antimalarial quinoline toxicity, and developing effective treatments.

Dr. Nevin said that, “This latter focus area should aim to develop treatable targets and treatments for patients with putative chronic quinoline encephalopathy – including those diagnosed with PTSD or TBI – to improve their health and lives." Dr. Nevin said in this respect that, “Although the committee wrote in its report that it held open sessions during their study to ‘listen to individual veterans and others, such as spouses and advocates, who are concerned about aspects of health that may be related to use of these antimalarial drugs’, the committee was prohibited from reviewing patient reports."

"If the committee had been allowed or directed to review the medical records of affected veterans, their unmet clinical needs would have been apparent," said Dr. Nevin.

About The Quinism Foundation

The Quinism Foundation, founded in January 2018, in White River Junction, Vermont, promotes and supports education and research on quinism, the medical disorder caused by exposure to quinoline drugs, including tafenoquine, chloroquine, hydroxychloroquine, and mefloquine.

Dr. Nevin is a board-certified occupational medicine and preventive medicine physician and former U.S. Army medical officer and epidemiologist. He is author of more than 30 scientific publications on malaria and the quinoline antimalarials, including “Screening for Symptomatic Mefloquine Exposure Among Veterans With Chronic Psychiatric Symptoms," published in the journal Federal Practitioner (https:// https://www.mdedge.com/fedprac/article/132560/mental-health/screening-symptomatic-mefloquine-exposure-among-veterans).

References

1. National Academies of Sciences, Engineering, and Medicine 2020. Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis. Washington, DC: The National Academies Press. https://doi.org/10.17226/25688.

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