FDA Collects Singulair Suicide Stories

Labels protect the pharmaceuticals, not really the patient---most doctorswill not lame the adverse side effects from any medications. In every shooting incident in the schools, the individual was on anti-depressants---but of course, doctors blamed the shooting because they stopped the medication.

Labels protect the Blame the adverse side effects from any medications. In every shooting incident in the schools, the individual was on anti-depressants---but of course, doctors blamed the shooting because they stopped the medication.--Thats what they want us to believe-- THE TIME HAS ARRIVED FOR THE PUBLIC TO DEMAND ACTION FOR THE TURHT AND ETHICAL VALUES IN PATIENT CARE! STOP LOBBYISTS FROM INFLUENCING CONGRESS

The FDA will collect a bunch of evidence and side with Big Pharma because that's who pay them on the side...

Watching all the TV ads, it is nearly impossible to not become desensitized to possible side effects. They state them as if they are saying you're getting two scoups of raisins.

"The info is also on a Singulair web site, but some pharmacists still dispense from older shipments delivered before the label changes, the Times-Union writes."

Does anyone know at what point a dispensed drug _must_ contain an updated label according to FDA regulations?

How sarcastic everyone is.

Every product has side effects, nothing is 100% safe. If you want the benefits, you take the risks. If you want perfectly studied products, wait 10 years longer than now for data that may be better but never perfect. If you don't like what you read, don't take the product.

Good grief - Hard to believe we're back to "all drugs have dangers"......

Issue always is, and always has been, whether docs and pts are accurately informed about risks/benefits in something approach "real time" - when company knew.

That's pretty much all there is to it. Truly.

The problem with not liking what we read, and not using the product is that the box warnings are rarely seen - the print is tiny (almost microscopic).....The larger point is that patients depend on their doctors to relay this information, and this is rarely done.

The free lunches, and gifts need to come to a quick-end....sure, it's just a few tickets to the baseball game....right?

The major pharmaceutical companies spend over $8,000 dollars per year, per doctor marketing their goods....and doctors are seeing patients every fifteen or twenty minutes...the doctors are getting their information from guys who are selling it...no exactly ideal, wouldn't you agree?....

It really comes down to some pretty weak links in the chain....from the FDA officials not having to hold to the same standards as medical students (that's right - not even the standards of 'students' in medical school), to doctor who are so inundated with patients, they have little time to read and study the many drugs they prescribe....to big pharma - who has as its main goal - profits....(understandably, we live in a capatalist system)....

Frankly, I think much of it has to do with morals - as my dad used to say 'Do the right thing'. The right thing is to err on the side of caution - to stop doing everything possible to prevent black box warnings, stop paying every congressman and his brother to get dangerous drugs through the process, to demand higher standards of the FDA, or disban it altogether....

Read the labels? Point well taken....at least to some extent....but, not when kids start dying - it ain't enough.....Pharma has not earned the trust of the American people - who cares what their warnings say?

It's much like listening to a bank robber tell you to watch your head while you climb underneath the teller window for protection....

Duane

"Good grief - Hard to believe we’re back to “all drugs have dangers”……"

Next it will be "Well you know that allergies cause suicide" :eyeroll: This is about a drug that NO ONE would ever think that suicide would be a risk.

JIM and Laurie, What are you guys griping about? Paul's statement was perfectly true. This was completely unexpected from what I understand. There has been no accusations of foul play. All drugs do have dangers. This may be a real danger of this drug. It's good that it is coming to light.

On a more scientific note, generally we don't take brain penetration of drugs into account unless we are TRYING to get brain penetration. (ie for a psychoactive drug) I wonder if all these suicidality reports will cause drugmakers to purposefully go after drugs that do not cross the blood-brain barrier for treatment of most diseases.

This could easily be twisted into a market ploy too. What would you say if a "new" version of Singular came out that was proven NOT to cross into the brain? Presumably, there would not be any suicidality problems. Could that be used to justify the high price of a new brand-name medication over a generic Singular? Maybe all these psychiatric side effects of current medications will work in FAVOR of big-pharma over the next 5-15 years as we slowly develop drugs that avoid these types of CNS side effects. Suddenly big-pharma will be showing new data that all theolder generic drugs result in increase suicidal thoughts while the current branded drugs do not. Mmmm... Maybe people will be singing a different tune about "cost vrs. benifit" when this occurs...

(and I assure you, it will occur! I'm a project leader of an early stage inflammation project -- you can be confident that I will be testing my compounds for brain penetration and will view it as a "plus" when compounds do not enter the brain. I’m sure I’m not the only researcher thinking about it…)

Hi Nathan - Speaking for self, I thought I was getting the old "you take your chances" stuff, and the business about people expecting risk-free drugs, etc.. Very, very tired rhetoric.

So, again speaking for myself, I was pointing out the irrelevance of the above (and its overall silliness).

There may be a few second-graders who want risk-free drugs, but most of us just want our docs, and ourselves, to be informed of _known_ risks/benefits in a timely and appropriately accurate way. That's all.

When problems arise, it is usually because that does not happen. And most of the serious delinquencies - certainly those deserving of blame - concern information that is, in one way or another, delayed, denied, spun, suppressed, camoflaged, etc.

Not complicated.

Laurie "Next it will be “Well you know that allergies cause suicide” :eyeroll: This is about a drug that NO ONE would ever think that suicide would be a risk."

Not true. I remember having a conversation about just this topic with an expert in inflammation at the time these drugs were being launched.

It is also in the top three of complained about medications at medications.com.

People don't like it when their kids take a medication for asthma and it makes them depressed or they kill themselves.

Reminds me of the quote about Serevent and people "dying while clutching their inhalers."

http://www.beforeyoutakethatpill.com/2008/3/if-they-dont-kill-us-they-will-drive-us-crazy.html

Doug Says: "Not true. I remember having a conversation about just this topic with an expert in inflammation at the time these drugs were being launched."

Three things: 1) I went to your site and found no evidence that these risks would have been anticipated. As far as I can see based on the evidence you supply, these risks popped up "out of the blue". Prior to these reports of psychiatric problems, did anyone have evidence that Singular even crosses the blood-brain barrier? 2) What is this conversation you are talking about? Are you saying that an "expert in inflammation" told you that he/she expected psychiatric problems with Singular? If so, why wasn't the FDA or Roche anticipating similar problems? Are you implying that some funny business was going on? 3) In incorrectly thought based on some of your previous posts that you were "balanced" in your thinking about pharmaceuticals. It's clear based on your website that is just not the case. I'll quote the first couple lines of your website in case anyone is interested. I've just completely lost any interest in this book you published... "Now it looks like Merck is going to join the rosters of pharmaceutical companies like Hoffmann La Roche that make drugs that, if they don't kill you, at least will drive you crazy. Roche has specialized for years in making drugs with psychiatric side effects like depression and suicidality,"

I hope you were trying to be funny with the above statement -- but humor really doesn't suit the subject you are trying to broach.

Dr. Doug,

Purchased your book at my local Borders,.. Its larger than I thought. My review will be forthcoming.

Doug - I also look forward to reading your book.

This takes us a bit off-topic - but not _too_ far. I was reading on your blog about WOSCOPS and the interpretation of prostate cancers rates as "chance."

I have not kept up with very latest data on relative and absolute risk of cancers associated with statins in the context of primary prevention. I know that there are sites obsessed with it. But can you refer me to what you consider a good study and/or source on this?

Thank you!

Nathan First of all I don't think it is ever a good idea to give up a sense of humor. And yes I do try and write in a light hearted way, especially when it is a blog-- that is what blogs are all about. Maybe if pharma execs had a lighter approach we wouldn't have so many train wrecks right now. Second, the conversation was about the known role of systems involved in inflammation in the brain and the possibility of psychiatric side effects with a drug (like Singulair) that affects inflammatory processes. The other example would be Accutane (acne drug) which is a retinoid. Yes someone dropped the ball in not considering that it could affect the brain and cause depression given the known fact that retinoid systems are in the brain.

Alsheikh-Ali et al 2007. This study found a correlation between magnitude of lipid lowering and cancer risk. It was a meta analysis. I think the take home point that the 'super' lipid lowering (e.g. LDL<100) that has been advocated by some more recently is potentially a risk.

Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer: Insights From Large Randomized Statin Trials. Journal of the American College of Cardiology 2007; 50:409-18.

Also the PROSPER study showed a 25% increase in cancer risk in men over age 70.

Doug says: "Yes someone dropped the ball in not considering that it could affect the brain and cause depression given the known fact that retinoid systems are in the brain."

Consider this: A study in 2001 showed that Singulair does not cross into rat brain. Plasma concentration of metabolites are undetectable in adult and child plasma. (in other words, metabolites couldn't really anticipate any CNS problems) It was well tolerated for 1 week at 20 times the clinical dose.(Clinical & Experimental Allergy Reviews 1 (3) , 254–260)

Based on this, I assume that it is highly unlikely that Singulair or one of its metabolites (which are more polar that Singulair) would get into the brain. That leaves us with the possibility that Singulair or its metabolites blocks a process important for some sort of hormone that transmits signals to the brain. Possible? Yes, certainly. Is it something easy to look for or easy to anticipate? Absolutely not.

So are you suggesting that all anti-inflammatory agents have the possibility of causing depression? What is it about Singulair that makes you more concerned than other anti-inflammatory agents? Singulair is not a retinoid and really isn't all that structurally related to accutane (although there are similarities)

Nathan,

You sure have peaked my curiosity,..Hormones. As you know women can be quite hormonal!!

no, retinoids are a different category than factors involved in inflammation. And the FDA is investigating all drugs in the Singulair class.

Doug, you didn't answer the question. Above, you essentially stated that Merck SHOULD HAVE known to look for long term psychiatric effects. (Merck "dropped the ball") Yet you cannot provide any tangible evidence to back that assertion up. I've provided evidence that I believe shows that this type of effect is completely unanticipated from what was previously known about the drug. Maybe I'm missing some key piece of information here...

Singulair is a leukotriene receptor antagonist and leukotriene receptors occur in the brain. There is a well established research relationship between inflammatory processes and depression.

"Singulair is a leukotriene receptor antagonist and leukotriene receptors occur in the brain. " Yes, but I just showed that it likely never reaches the brain!

Nathan do you have any ideas why montelukast might cause CNS side effects? I'm just curious. You seem like the true expert here.

JIM: For the updated labels the company needs to send out the updated label practically immediately (a matter of days), but the pharmacy won't get it until they need to reorder from the wholesaler, and the wholesaler will first need to deplete their stock with the existing old label. I also doubt the pharmacist will actually read the new label or notice the change.

Ironically, or at least in contrast to what people here might think, a label change that does not necessitate a dear doctor label, will probably get out fastest through a sales rep compared to any other channel.

"Paul How sarcastic everyone is. Every product has side effects, nothing is 100% safe. If you want the benefits, you take the risks. If you want perfectly studied products, wait 10 years longer than now for data that may be better but never perfect. If you don’t like what you read, don’t take the product."

I guess that means that the antidepressants have been so perfectly studied that it is time to pull them from the market. After 20 years of no benefits and all risks. I also remember reading that the antihistamines are related to antipsychotics and antidepressants.

I guess it is too much to ask for some PhRMA sympathizer (apparently) like Paul to care if people die from a drug.

When I took Zoloft and complained of becoming homicidal and suicidal on the drug, I was told to take more of it, and then again more. Then Zyprexa. Luckily I kicked that killer drug and my shrink and OBGYN to the curb.

You can't trust anything from PhRMA and nothing ever fails to surprise me. I don't think up to this point that the drug label for Singulair said anything about causing suicide, so how were people supposed to read the label and know not to take it?

It's all about running through a field of flowers without allergies, not about overcoming depression, so nobody would ever think "Gee, maybe my suicide attempt was because of the Singulair" up until the time at which people begin to realize that PhRMA is full of it and will not raise an eyebrow if a clinical trial results in a few deaths, or if they notice them in the MedWatch system either.

"It was well tolerated for 1 week at 20 times the clinical dose."

My original comment was also directed at Pauls "all drugs have side effects" comment.

Now, on the above quoted statement...how does that time period of testing in anyway convert to real life use? Singulair is prescribed for allergy seasons...much longer than 1 week, albeit at lower doses. Could it be that at the "recommended dose" over a normal use period allowed the brain barrier to be crossed, something that would not have shown in such a short term trial.

Well as an allergy sufferer for 30yr's, which started as seasonal and is now pretty much all year long, I can say for myself I'd much rather blow my nose 20 time's a day than risk ending up with any of the side effect's I see along with the advertisement's on tv I have one problem I'm used to dealing with and don't need posibly five more on top of it...........and my symptom's are quite severe at time's

My question on all of this is why do we use so much montelukast anyway?

For allergic rhinitis it is - at best - a third line drug. Intranasal steroids are recommended in most every set of guidelines as having the greatest efficacy for allergic rhinitis symptoms. If used properly - and there is a correct way to spray these into the nose - they are extremely well tolerated and highly effective. There are only a few patients/conditions in whom they you should not be used. After that, there are less-sedating antihistamines. Yes, there are histamine receptors in the brain too, but some products have minimal/negligble brain penetration (fexofenadine is probably the cleanest from the CNS perspective - it is also true that the original antipsychotics led to the first antihistamines).

You can "treat" allergies by avoidance, and minimize the symptoms with nasal saline sprays/irrigation - if you want to go all "whole-grain" on the issue. There is always immunontherapy - though there is not evidence for the "allergy drops" which some advocate.

For asthma, monetlukast's role (accoring to the NIH-NHLBI National Asthma Education and Prevention Program's Expert Panel) is pretty constrained as well. In this situation it may be an alternate treatment (categorized along with cromolyn, theophylline, etc.), but it is specifically not a preferred controller treatment for children or adults. It may be a useful adjunt treatment along with regular (daily) use of an inhaled steroid in children or adults. However, in adults the first adjunct treatment should be a long-acting beta agonist. (This makes Advair and Symbicort second-line agents. This is still true even if Advair has been very successfully marketed - it still is an asthma controller with a "black box" warning relating to the disease it is supposed to treat.) The data aren't there to make recommendations in children on whether or not montelukast or an LABA should be used as the best adjunct.

Montelukast use alone as an asthma controller is associated with higher rates of asthma exacerbations as measured by rescue inhaler use, steroid use, etc. The studies I've seen show a higher financial and patient outcome cost with the use of montelukast compared to inhaled steroids.

Don't missunderstand, there are still problems with getting paitents to use any asthma controller with regularity. Some argue that montelukast offers an advantage due to once daily oral dosing. In a study of adherence, there were in fact more missed doses of the twice daily steroid. However, when the data were examined for missed days of therapy, montelukast. So even with imperfect adherence, paitents with inhaled steroids still had more days receiving some controller treatment than did the montelukast patients.

I'm not really sure what to say about the exercise-induced asthma indication, except that generally if a patient with asthma needs a controller for exercise-induced symptoms, it is a good bet that there is some unappreciated persistent symptoms. If so, this would be better treated with an inhaled steroid.

So that just leaves a little niche for montelukast - It is good for the odd syndrome of nasal polyposis, aspirin/NSAID induced bronchospasm/sensitivity, and urticarial conditions (which also require the use of other agents). Oddly, the product does not have any indication of which I'm aware for any of these conditions.

You will note that montelukast is one of those products which proves my rule of DTC advertising. This is a rule I share with patients - If it is advertised on TV, it must not be that good. If it were that good, the company would not need to advertise it.

I'm not saying that montelukast doesn't help some people. I'm also not saying that it is a bad drug. But I am saying that this drug is successful more for it's marketing than it's clinical benefit. Of course this is true of many drugs.

I will remain (as always) skeptical about this possible link, until there are more data available. But in truth, I don't think even a definite link will have much effect on sales of montelukast. The marketing (or Kool-Aid) has been very good. As we used to say: "strong work" for Merck.

Several conversations going on at once here...

Jack2 - Thanks for your response, which was interesting and informative.

It's a somewhat arcane point, but it raises a question related to our Michigan preemption law. One clause notes that preemption does not apply if the labeling of a drug in question is not in compliance with FDA regulations at the time of sale. Even if a Dear HCP had gone out, the backlog stock might well be misbranded in that sense.

More generally, I am assuming there is often a considerable amount of stock limited only by expiration dates. And thus, despite whatever is learned via detailers or other communications from the company, it sounds possible that months could go by in which misbranded drugs are dispensed.

The proof is in the pudding as they say. The fact that a drug company files a patent on a similar chemical structure to montelukast for neuro-psychiatric disorders shows that there is indeed a direct connection between inflammation processes and depression. The problem is that there are genetic variants in these particular receptors. AND, the variants can be very different to the extreme of almost being opposite. Think about the fact that stimulants are very helpful in treating ADHD. The same drugs that help those with ADHD calm down and focus would make others climb the wall.

We have a lot of learn and should never be closed minded. We should always listen, observe, and think. We don't know everything and never will.

This is the description of the patent for a chemical structure very close to montelukast.

" The compounds of formula I have a good activity on the 5-HT.sub.5A receptor. Therefore, the invention further provides methods for the treatment of depression (which term includes bipolar depression, unipolar depression, single or recurrent major depressive episodes with or without psychotic features, catatonic features, melancholic features, atypical features or postpartum onset, seasonal affective disorders and dysthymia, depressive disorders resulting from a general medical condition including, but not limited to, myocardial infarction, diabetes, miscarriage or abortion), anxiety disorders, (which includes generalized anxiety and social anxiety disorder, panic disorders, agoraphobia, social phobia, obsessive compulsive disorders, post-traumatic stress disorders, psychotic disorders (which includes schizophrenia, schizoaffective disorders, bipolar disease, mania, psychotic depression, and other psychoses involving paranoia and delusions), pain (particularly neuropathic pain), memory disorders (including dementia, amnesic disorders and age-associated memory impairment), disorders of eating behaviors (including nervosa and bulimia nervosa), sexual dysfunction, sleep disorders (including disturbances of circadian rhythm, dyssomnia, insomnia, sleep apnea and narcolepsy), withdrawal from abuse of drugs (such as of cocaine, ethanol, nicotine, benzodiazepines, alcohol, caffeine, phencyclidine and phencyclidine-like compounds, opiates such as cannabis, heroin, morphine, sedative hypnotic, amphetamine or amphetamine-related drugs), motor disorders such as Parkinson's disease, dementia in Parkinson's disease, neuroleptic-induced Parkinsonism and tardive dyskinesias, as well as other psychiatric disorders and gastrointestinal disorders such as irritable bowel syndrome (WO 2004/096771). "

******

http://www.freshpatents.com/2-aminoquinoline-derivatives-dt20080403ptan20080081907.php

My 12 year daughter,has been on Singulair since last year. Over the course of the year, she has grown more anxious and starting talking of suicide at the end of May. That very day she stopped taking it. We have her seeing a counselor and she is getting better. I feel I need to share this because I do believe there could be a link. We are sticking very close to her right now but you just never know.