Lariam Bites the Dust—Almost.
Replies: 23 - Last Post: May 9, 2012 11:18 PM Last Post By: tsr24
Feb 8, 2012 9:42 AM
Lariam Bites the Dust—Almost.An interview with the man who blew the whistle on the neurotoxic malaria drug in the U.S. Army’s kit bag.
A dangerous malaria drug invented by the Army and commonly used by soldiers and civilians alike causes everything from episodes of psychotic violence to nightmares more real than reality, and is finally being withdrawn as the first-line treatment for troops in malarial zones.
Largely due to the efforts of Dr. Remington Nevin, a medical epidemiologist and a physician in the U.S. Army, who went public about Lariam’s potential for causing psychological illness, military officials announced in December that the Army was done with Lariam as a first-line malaria preventative except for “special circumstances.” In the past, such special circumstances have allegedly included its use as an interrogation drug at Guantanemo.
Dr. Remington Nevin: I am speaking to you in an individual capacity, and my opinions are my own and in no way reflect those of the U.S. Army or the Defense Department.
—Can you lay out what you know about mefloquine causing hallucinatory and dissociative effects in travelers who take it for malaria?
Dr. Nevin: The symptoms closely mimic those of a condition known as anti-NMDA receptor encephalitis, which an expert in the field, Dr. Dalmau, describes as including "anxiety, fear, bizarre or stereotypical behaviour, insomnia, and memory deficits". It is thought that rising levels of antibody to the NMDA receptor induces… widespread downstream dysregulation of limbic dopaminergic and noradrenergic tone, which ultimately are responsible for producing the syndrome's psychotic effects… This limbic dysregulation may also be similar to what is seen with the chemical NMDA receptor antagonists, including ketamine and phencyclidine, which share with mefloquine a particular propensity towards impulsivity and dissociation. For these reasons I conclude that mefloquine should be characterized as a dissociative hallucinogen.
—Why was the Army so slow to move on mefloquine?
Dr. Nevin: To put things in perspective, understand that mefloquine is the sole product of an aggressive 20-year, multi-million dollar effort by the U.S. Army. Mefloquine was identified only in the early 1970s after tens of thousands of other quinoline compounds had failed toxicity and efficacy tests. By the time of mefloquine's U.S. licensure in 1989, it was essentially DoD's last and only hope. So, if I could rephrase your question, if mefloquine is as safe as the Army once claimed, then why is it no longer the drug of choice? If we assume that this quiet policy change was made in tacit acknowledge of safety concerns, then the question is, precisely what new information has informed this decision, why has this change taken so long to occur, and most importantly, what harm might this policy change now be seeking to avoid, which may already have accrued among those in whom the drug had been previously used?
The reasons for the Army's silence on these questions are likely quite banal. Admitting mefloquine is a dangerous drug would be a bitter pill for any Army medical leader to swallow. Many of today's senior medical leaders were intimately involved in the studies that saw the drug rise to prominence, and many are on record over the previous decades publicly defending the drug against the increasingly validated claims of its earlier critics. Absent external pressure to do so, it is likely of little benefit for these senior medical leaders to suffer the humiliation that would come from admitting what they might now otherwise privately concede. Saying nothing is the path of least resistance on their journey to a comfortable retirement.
Read the full story here.
Feb 8, 2012 8:26 PM
1Sorry I missed out on all those fun "recreational" uses of mefloquine. Funny that I've never met anyone who even thought about doubling the dosage for the sake of bigger and better hallucinatory effects....but maybe the writer's sources hang with a different crowd.
Leaving aside the vague, unsubstantiated and deliberately inflammatory tone of the article itself, do you happen to know what anti-malarial the US military has switched to?
Thanks for any clarification.
Feb 8, 2012 8:38 PM
2Malaria policies for the US military Doxycycline is the drug of first choice in cloroquine-resistant areas. Mefloquine may be given to someone who cannot take doxy and who has no contraindications for mefloquine.
Feb 8, 2012 10:25 PM
Feb 8, 2012 10:38 PM
4Sorry, it's not really worth my time. I noted that the article consisted almost entirely of assertions in the absence of supporting evidence. Anyone can assert whatever they please; they might be correct, or not.
If you read the article and find ample specific and substantiated statements of fact, we'll just have to blame my inability to spot them on the many, many mefloquine pills I've taken over the years. After all, mefloquine causes brain damage, mental illness and other such. I'm probably beyond redemption.
Feb 8, 2012 10:46 PM
Sorry, it's not really worth my time. I noted that the article consisted almost entirely of assertions in the absence of supporting evidence.
Did you read the texts hyperlinked to the blog entry? Now I'm not the author, but I simply cannot follow your allegations. Indeed, some of the comments in the interview are without sources, but that's rather normal for journalistic interviews. Please feel free to read Dr. Nevin's publications in peer-reviewed medical journals for further information though. Considering your allegations, I think you should really take the time.
Feb 9, 2012 12:33 AM
6I can't. I keep getting distracted by the links to other peer-reviewed research which appears at odds with the stuff you favor. Take this one, for example: http://www.ncbi.nlm.nih.gov/pubmed/17519415, or this one: http://www.ncbi.nlm.nih.gov/pubmed/21143906, both of which I chose at random from the "related citations" box . Or read the last one on the list you offer above, which states that the rate of potential contraindications for mefloquine use is 9.6% among soldiers. Or the one above it, which proposes that the list of contraindications be expanded to include certain conditions not currently included. Etc. etc. etc.
This is all wonderful stuff. I don't have the time to pursue it. Maybe you do, in which case I'll gladly read your critical summary provided it also includes alternate points of view, of which there are many supported by (published, peer reviewed) research. Try not to cherry pick too vigorously.
I do have the time to notice that Dr. Nevin has a thing for mefloquine, which might or might not be born out by further research. However based on my very quick perusal the claims (unsubstantiated in the article you linked) made do not appear to correspond to the actual results of the studies you refer to.
I'll look for that critical analysis. There's no hurry; it does take time.
Feb 9, 2012 1:04 AM
7Thanks, Mark. Unfortunately you forgot to mention the authors' conflicts of interest. Let me quote:
"The position of mefloquine as a 21st century malaria chemoprophylaxis.
Patricia Schlagenhauf,corresponding author1 Miriam Adamcova,2 Loredana Regep,2 Martin T Schaerer,2 and Hans-Georg Rhein2
1 University of Zürich Centre for Travel Medicine, Hirschengraben 84, University of Zürich, Switzerland 2 F.Hoffmann-La Roche, Basel, Switzerland
This paper is based on data collated for an F. Hoffmann-La Roche regulatory update. PS was the external consultant who received consultancy fees for preparing the regulatory update. PS has also received research funding and/or speakers' honoraria from GlaxoSmithKlein, F. Hoffmann-La Roche and Pfizer.
MA, LR, MTS, HGR are employees of F. Hoffmann-La Roche, Basel, Switzerland"
"Controversies and Misconceptions in Malaria Chemoprophylaxis for Travelers
Lin H. Chen, MD; Mary E. Wilson, MD; Patricia Schlagenhauf, PhD
Financial Disclosures: Dr Chen reports that she has received honoraria for serving on the editorial board of Travel Medicine Advisor, AHC Media LLC. Dr Schlagenhauf reports that she has received research funding honoraria for speaking at conferences from F. Hoffmann La Roche and GlaxoSmithKline and consultancy fees from F. Hoffmann La Roche. Dr Wilson reports no conflicts of interest. "
You also forgot to mention the methodologically more rigorous Cochrane Review which was written by authors without important conflicts of interest. As you're interested in a detailed analysis, my suggestion is to get copy of the full text in your local library or to buy it online. Should you have further questions after reading it, please feel free to ask.
By the way, I would very much appreciate a more polite, less inflammatory tone. Thank you!
Feb 9, 2012 10:48 PM
8Cool! You're either skilled at critical inquiry, or you already knew. Either way, you seem to care deeply about the subject--deeply enough to read widely and incorporate both sides of the picture into a single summary. Don't forget that part about "incorporate both sides."
See, I really don't care that deeply, so when I check the first layer of what you're offering, note that it's one-sided and therefore highly suspect, I dismiss it and move on. You're not going to convince me or anyone else with any degree of insight by posting one-sided screeds; nor should you expect to. If you want to change minds, offer up something which demonstrates respect for your audience.
Or not: it's entirely up to you, of course. A certain percentage will believe you no matter what evidence you offer, so if that's your target audience you need not exert yourself any further.
Feb 10, 2012 4:28 AM
9Mark, your persisting aggressiveness and your personal digs certainly tell a lot more about yourself than they tell about me.
Anyway, as you said, you're interested in a well balanced scientific review on mefloquine. Therefore my advice for you is to get yourself a copy of the Cochrane Review. In medicine, Cochrane Reviews are usually considered the gold standard among systematic reviews. I'll happily discuss any further questions afterwards.
Feb 10, 2012 8:36 PM
Feb 11, 2012 12:14 AM
Feb 11, 2012 12:27 AM
Feb 18, 2012 3:00 PM
13So whats the alternative for those of us like me (white anglo-celtic australian) who is sun sensative at the best of times. Doxycycline made me so sun sensative I was sunburnt through my shirt. I am not a budget traveller but Malorin is out side of my price range - especially on extended trips. I have used Lariam on my last 3 african adventures with virtually no side effects - one night a poor sleep.
May 9, 2012 8:13 PM
14So guys...no need to get your panties in bunch. Mark, I applaud your skepticism, albeit rather blind to the real facts presented over the years, most notably a Lariam website called to "Lariam or not to Lariam". Grusdas, hurray for you, you have obviously met someone who has had the symptoms, or you have personally experienced them. Both sides are of the argument are needed. I'd put Mark on platoon patrol though first, and save Grusdas, because he might save my ass some day.
Lariam for whatever reason, and I'm not sure how or why has effected people. Thousands. Dr. Nevin, heroically, and academically, seeks to explain the nature of the actual development of Lariam, which is the start to something that can provide real results, not this he said she said baby bickering.
Fortunately, Mark, you are not an army doc. Thankfully, the US Army, has finally shed some light on subject that has been been mysterious and affected people. And fortunately, like the other armies around the world, the US Army has pulled this pill from the troops except for special situations, (I imagine acute malaria). Mark, I'd listen to the doc. After all it's pulled. I'm just saying. It takes one lapse in mental fortitude to have this drug take hold. And the testimony by the doc, is a very interesting testimony indeed. I hear you, Mark. And it's great that you haven't had any symptoms. However, that does not qualify you to disregard the incredible testimony of others, eye witnesses, docs, and loved ones who in some cases have lost loved ones. It's just a little to boy scouty for me and I'm a boy scout. So thanks doc, my grandpa WW2 doc would applaud you for exploring the many claims. And what I found most compelling, was that 20 years, $$ in the mils and different compounds were experimented with to find the one "least toxic". Wonderful. Mark. Smart people are smart for a reason. You are blow hard. Til you get hurt and cry for mommy. And have Nevin sew you up. Get a life, get a reason.
If anything Mark, the age old "Heart of Darkness" syndrome, could account for these lariam deals. However the abundance of the testimony, and the increasing diagnostic testing, may point to something more than just a mental breakdown. Think timid weed smoking college kids, not army like guys like you and I. Nevin is dead on balls. Guy should be the US General Surgeon.
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