Mefloquine tablets

While it may be tempting to attribute anxiety, depression, paranoia, or other mental health symptoms to the psychological effects of the COVID-19 pandemic, these symptoms may be an early warning sign of idiosyncratic quinoline neurotoxicity, and must be taken seriously.

WHITE RIVER JUNCTION, Vt. (PRWEB)
March 23, 2020

The Quinism Foundation has called on state boards of pharmacy to enact uniform restrictions on the dispensing of the quinoline antimalarial drugs hydroxychloroquine, chloroquine, mefloquine, primaquine, tafenoquine, and quinine to limit hoarding in response to the COVID-19 pandemic.

“State boards of pharmacy must take immediate action to protect the public’s health,” said Dr. Remington Nevin, MD, MPH, DrPH, a former U.S. Army public health physician and Johns-Hopkins trained psychiatric epidemiologist and drug safety expert, who now serves as Executive Director of The Quinism Foundation. “Inaction or delay will lead to shortages of these drugs, particularly hydroxychloroquine, for existing indications, and to the substitution of more dangerous quinolines, such as mefloquine, for off-label self-treatment and prophylaxis of COVID-19.”

“Although only chloroquine and hydroxychloroquine have demonstrated limited antiviral activity against coronavirus in published studies, and while hydroxychloroquine in particular has shown limited evidence of clinical efficacy, as highlighted by recent high-profile statements,” Dr. Nevin noted, “interest in other antimalarial quinolines has increased significantly as a result of a perceived common efficacy among drugs of the class.”

Dr. Nevin noted that such interest is not without basis. “All antimalarial drugs of the quinoline class are amphiphilic weak bases, which lead to their accumulation in acidic cellular endosomes, the property thought to at least partly underlie the observed antiviral activity of certain previously-tested drugs,” said Dr. Nevin. [1,2] “However, the same common properties that likely underlie the effectiveness of these quinoline antimalarial drugs against the virus may also underlie their common dangers.”

“While hydroxychloroquine is among the safest drugs of the quinoline antimalarial class, all antimalarial quinolines share a common toxicity,” said Dr. Nevin. [3] “In susceptible individuals, these drugs act as idiosyncratic neurotoxicants, potentially causing irreversible brain and brainstem dysfunction, even when used at relatively low doses. This drug-induced dysfunction causes a disease of the brain and brainstem called quinoline encephalopathy, or quinism, which can be marked acutely by psychosis, confusion, and risk of suicide, and by lasting psychiatric and neurological symptoms.”

“Symptoms of chronic quinoline encephalopathy include tinnitus, dizziness, vertigo, paresthesias, visual disturbances, nightmares, insomnia, anxiety, agoraphobia, paranoia, cognitive dysfunction, depression, personality change, and suicidal thoughts, among others, ” said Dr. Nevin. “Particularly among military veterans, in whom these drugs have been widely used for decades as prophylactic antimalarials, these symptoms can mimic and be mistaken for those of post-traumatic stress disorder and traumatic brain injury.” [3]

“During World War II-era studies, when many antimalarial drugs of the quinoline class were first synthesized, clinical researchers found that many caused a syndrome marked by psychosis, confusion, dizziness, and other psychiatric, cognitive, and neurologic adverse effects,” said Dr. Nevin. [4] “Other researchers studying the drugs’ toxicity in animals noted they caused widespread and irreversible neurotoxic injury to neurons throughout the brainstem and limbic system.” [5]

Dr. Nevin noted a recent report by an ad-hoc committee of the National Academies of Sciences, Engineering, and Medicine identified a critical need for additional research on the long-term effects of antimalarial quinolines. Dr. Nevin also emphasized that the Quinism Foundation has recently called on Congress to fund research into chronic quinoline encephalopathy. [6]

“Although antimalarial quinolines have been commonly prescribed and used by millions of people for prevention of malaria, and more recently, in the treatment of autoimmune diseases, a substantial minority will need to discontinue the drugs early during use owing to the development of prodromal neuropsychiatric symptoms,” said Dr. Nevin.

“Even hydroxychloroquine, which is commonly described as ‘safe’, is associated with reports of neuropsychiatric adverse effects comparable to those reported from mefloquine,” said Dr. Nevin [7], “including serious adverse effects such as neurotoxic vestibulopathy and psychosis.” [8,9]

Dr. Nevin noted that mefloquine (previously marketed as Lariam) now contains a boxed warning, cautioning of the need to immediately discontinue the drug at the onset of even seemingly mild symptoms such as abnormal dreams, nightmares, insomnia, anxiety, depression, restlessness, or confusion, as these may be considered “prodromal to a more serious event.” [10]

Dr. Nevin emphasized the importance of recognizing and properly reporting adverse effects from these medications to the U.S. Food and Drug Administration. “While it may be tempting to attribute anxiety, depression, paranoia, or other mental health symptoms to the psychological effects of the COVID-19 pandemic,” said Dr. Nevin, “these symptoms may be an early warning sign of idiosyncratic quinoline neurotoxicity, and must be taken seriously.”

Dr. Nevin noted that adverse effects from hydroxychloroquine, chloroquine, mefloquine, primaquine, tafenoquine, and quinine may be reported to the U.S. Food and Drug Administration’s MedWatch program, at

https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program.

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 family of medical disorders caused by exposure to quinoline drugs, including mefloquine, tafenoquine, and chloroquine.

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 “Neuropsychiatric Quinism: Chronic Encephalopathy Caused by Poisoning by Mefloquine and Related Quinoline Drugs,” published in the Springer Nature book, “Veteran Psychiatry in the US.”

(https://link.springer.com/chapter/10.1007/978-3-030-05384-0_20).

References

1. Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology journal. 2005;2:69.

2. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clinical infectious diseases. 2020. In press. doi:10.1093/cid/ciaa237.

3. Nevin RL. Neuropsychiatric Quinism: Chronic Encephalopathy Caused by Poisoning by Mefloquine and Related Quinoline Drugs. In: Ritchie EC, Llorente MD, eds. Veteran Psychiatry in the US. Cham: Springer International Publishing; 2019:315-331.

4. Nevin RL, Croft AM. Psychiatric effects of malaria and anti-malarial drugs: historical and modern perspectives. Malaria journal. 2016;15:332. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918116/.

5. Nevin RL. Idiosyncratic quinoline central nervous system toxicity: Historical insights into the chronic neurological sequelae of mefloquine. International journal for parasitology Drugs and drug resistance. 2014;4(2):118-125. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095041/..

6. The Quinism Foundation. The Quinism Foundation and Veterans for Common Sense Call on Congress to Fund Research into Chronic Quinoline Encephalopathy. March 9, 2020. Available at: https://quinism.org/press-releases/congress-research-chronic-quinoline-encephalopathy/.

7. Mascolo A, Berrino PM, Gareri P, et al. Neuropsychiatric clinical manifestations in elderly patients treated with hydroxychloroquine: a review article. Inflammopharmacology. 2018;26(5):1141-1149.

8. Chansky PB, Werth VP. Accidental hydroxychloroquine overdose resulting in neurotoxic vestibulopathy. BMJ Case Reports. 2017;2017:pii: bcr-2016-218786.

9. Ward WQ, Walter-Ryan WG, Shehi GM. Toxic psychosis: a complication of antimalarial therapy. Journal of the American Academy of Dermatology. 1985;12(5 Pt 1):863-865.

10. Nevin RL. A serious nightmare: psychiatric and neurologic adverse reactions to mefloquine are serious adverse reactions. Pharmacology research & perspectives. 2017;5(4):e00328.

ASKP Weighs in on Ketamine Therapy against the backdrop of the COVID-19 Pandemic

Ketamine therapy will continue to be a vital service that needs to be available to patients during this pandemic. – Dr. Sandhya Prashad, Secretary of the American Society of Ketamine Physicians

BELLAIRE, Texas (PRWEB)
March 23, 2020

It goes without saying that COVID-19 is on the minds of nearly every American. The societal and economic disruption is almost without precedent. As government officials and clinicians wrestle with issues of how to protect the public, there seem to be more questions than answers. The mental health effects of COVID-19 are as important to address as are the physical health effects. Social isolation, school closures, lack of structure, financial difficulties, and unemployment are among the many stressors related to COVID-19 that have significant impacts on mental well-being.

In a national survey conducted by Axios, 29% said their emotional well-being had gotten worse. Chris Walden, co-founder of Ketamine Media, reports that online searches for anxiety treatment, depression treatment and searches pertaining to suicide, have increased at a rapid pace. In addition, Noah Heller, co-founder of MoodMonitor, has noted that the number of patients reporting thoughts of wanting to inflict self-harm via a depression rating tool, the PHQ-9, has significantly increased. Research has shown that suicidal ideation reported on the PHQ-9 was a robust predictor of suicide attempts and deaths. In addition, there is significant literature establishing a strong link between unemployment and higher suicide rates. Many studies have demonstrated the robust and rapid antidepressant and anti-suicidal effects of ketamine, especially in a treatment resistant population. Awareness and access to this valuable treatment will be increasingly important as unprecedented stressors increase the rate of depression and suicide in the coming months.

The American Society of Ketamine Physicians has been at the forefront of advocating for patients who have benefited from this forward-leaning therapy. Ketamine therapy is an essential service that cannot be interrupted during this crisis. “Our patients who suffer from severe depression and suicidality do not suddenly get better just because there is a pandemic. In fact, they are likely to struggle more. Continuing to offer treatment to high risks populations significantly alleviates the additional strain that would otherwise be placed on emergency rooms and urgent care settings,” says Sandhya Prashad, MD, a psychiatrist from Houston and Secretary for ASKP.

Taking appropriate precautions while continuing to treat patients in an outpatient setting is imperative. Evaluating the necessity of treatment for patients beforehand can be beneficial. The use of telemedicine can assist in evaluating and providing ongoing care for patients in less emergent situations. Minimizing contact between patients in waiting rooms, screening patients beforehand for symptoms or contact with others who are ill and thorough cleaning between patients can help to mitigate the risk to patients and staff.

About ASKP

The American Society of Ketamine Physicians is a medical society that embraces the leadership roles of psychiatrists, anesthesiologists, emergency medicine physicians, psychotherapists, advance practice providers and others in the therapeutic use of ketamine. For more information on the American Society of Ketamine Physicians, visit http://www.askp.org.

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