Tuesday, February 21, 2012

Assuming Facts Not in Evidence II - Sleeping Medications

As I described in my post of January 31:

One marketing technique used by big Pharma to mislead physicians is the engineering of a journey of ideas that have never been proven into the clinical lore as if they were established facts.  So-called experts who are paid off by drug companies make presentations at continuing medical education conferences or write "review" articles for medical newspapers or throwaway journals in which they mention these so-called "facts."

In these situations, conditional phrases are said or written as a quick aside in order to leave the speakers and writers a loophole just in case a member of the audience challenges them about overstating their case. Should this happen, the speakers are then able to point to the conditional language they used and “remind” the audience that their use of this language indicates that they are not making spurious claims.  

Most of the time, however, no one in the audience will make such a challenge. The audience is left with a dangling implication that the statement is an established fact. The non-discerning physician comes away with the “take home lesson” that the assertion is true.  Research has shown that most people only remember one or two salient points from a paper or an oral presentation anyway.

I have also written about how I suspect (but cannot prove), that drug companies begin to actively spread negative information and even disinformation about drugs as soon as most brand-named drugs in a certain class become available generically.  As I wrote in my post of October 19, 2011:

Pharma-inspired or paid-off writers denigrate highly-effective drugs (antidepressants and benzodiazepines) that just happen to have gone generic, in hopes that doctors will prescribe more expensive, potentially more toxic, and less effective brand-named drugs (particularly atypical antipsychotics). 

It amazes me how drug companies have only now been releasing negative information (that had apparently been held back from the public previously) about SSRI anti-depressants -since they have been available since the mid-1980’s.

I had seen this sort of thing done before to a class of drugs called benzodiazepines, which are demonized as being far more addictive than they actually are.  Interestingly, this demonization of the drugs started anew with the introduction of three new sleeping medications (Ambien, Lunesta, and Sonata) that, although slightly different in chemical structure than benzodiazepines, do exactly the same thing in the brain.  (Ambien has gone generic, but Pharma sells a delayed-release version that is still brand named.  As we shall see shortly, this type of formulation directly undermines one of their claims - that the new drugs are safer than the old ones).

Benzodiazepines include such popular drugs as Valium, Librium, Klonopin, Ativan, Xanax, Dalmane, and Restoril.  Ambien, Lunesta, and Sonata  are technically not benzodiazepines, but they might as well be.  They are called non-benzodiazepine benzodiazepine receptor agonists.  Loosely translated, this means that they affect the same nerve cells in exactly the same way as benzodiazepine benzodiazepine receptor agonists.   

They offer no advantage in terms of addictive potential, side effects, or efficacy.  In fact, they offer some real disadvantages.  They are far more likely than the old benzo’s to cause people to do things in their sleep that they do not remember the next day, including cooking large meals and even driving significant distances!  Also, if you take Ambien and force yourself to stay awake, you get really high.

As an aside, most of the public, and many physicians who should know better, believe that some benzodiazepines are tranquilizers, while others are sleeping pills.  An old joke asks, “What is the difference between a tranquilizer and a sleeping pill?”  The answer: marketing. 

Most outrageously, the drug companies successfully lobbied the government to have benzodiazepines excluded from the Medicare drug benefit program – the only major class of drug so excluded – while not excluding the new, more expensive brand named sleepers!  This law has finally been changed to allow for the old drugs, but that change will not take place for some time.

Pharma shills have fanned out to convince everyone that the new drugs are both safer and more effective than the old ones.  With success. I frequently see physicians who seem to think that benzodiazepines are the scourge of the earth due to their addictive potential prescribing the new drugs with abandon (not to mention prescribing much more serious drugs of abuse such as stimulants).

Now, that the new drugs are better and safer is one of the widely-disseminated “established facts” that are not really facts at all.  Again, I am going to pick on an article in the psychiatrist newspaper, the Psychiatric Times.  I do so reluctantly because this publication often prints more balanced articles, but lately it has been just feeding me blatant examples of points I’m trying to make in this blog.

The article in question appeared in the January 2012 edition of the paper and was entitled, “Treatment of Insomnia in Anxiety Disorders.”  It was written by Gregory Asnis, Elishka Caneva, and Margaret Henderson.

In discussing pharmacological treatment of insomnia, they say, and I quote, “Not only are the non-benzodiazepines effective [that part is true], but there is a notion that they are safer than benzodiazepines.”  They give two reference here I will discuss shortly.

A notion?  Notice they are not actually saying here that the drugs are safer.  As I mentioned above, they do try to leave themselves an out.  However, the authors go on to make a stronger statement: “Although head to head studies comparing these classes of hypnotics have been minimal [If that’s true, than how can they draw conclusions], a recent metanalysis supports the findings of reduced adverse effects for the non-benzodiazepines.”  They give a third reference.

They explain that the new drugs have a shorter half-life, and therefore cause less residual daytime sedation, and “other  [unnamed] adverse effects."

Without even looking at the reference, they are already spouting complete bullsh*t here that strongly suggests that the new drugs are better.  So what about half-lives of the drug?  Half life is the number of hours it takes for the body to excrete 50% of an ingested drug from the body.  In truth, the different old benzodiazepines on the market have a wide variety of different half lives. 

Some of them such as Xanax have a very short or even shorter half life than the new drugs.   Some have a mid-range half life such as Tranxene. Some have a very long half life like Klonopin and Valium.  If daytime sedation is a problem, the doctor can either reduce the dose, or prescribe a shorter acting drug!  There is no need for the more expensive alternative.  If you take a delayed release preparation so you sleep through the night, then you would face just as much daytime sedation as if you took a benzo with a longer half life!

Not only that, but the shorter the half life of a sedative, the more addictive it is.  Furthermore, the shorter the half-life, the more the drugs are likely to cause “rebound” insomnia if suddenly discontinued. So, if the authors of this article are touting the importance of short half lives, perhaps they should also mention these facts, which are well known among addictionologists.  Funny that they did not, isn’t it?

So what about the meta-analysis?   I’m glad you asked, since I found it and read it.  It says quite clearly that, in the studies they are pooling, the drugs were analyzed irrespective of their differences in half life, potency (how the drugs compare in strength milligram to milligram) or dosages.  

There were no indications in direct comparisons indicating that the new drugs were safer.  There were some “indirect comparisons” (whatever those are) that were made that seemed to indicate that the new drugs were slightly safer, but again, since half life, potency and dosage were not considered, what the hell does that even mean?

Also noteworthy is that the studies meta-analyzed were in people who did not also have an anxiety disorder.

As for the other two “references,” one of them clearly attributes the results of studies that showed fewer side effects in the new drugs to their shorter half-lives.  The other never really clearly states that the new drugs are preferable to the old benzodiazepines at all, although it also discussed issues concerning drug half lives.

Let the buyer beware, baby.


  1. Amen, Dr. Allen. One day I will share with you how I had to trump my own doctor with a surprise from out in left field, that enabled me to cut through a Catch-22. The Catch-22 I encountered is that typical, responsible psychiatrists don't want to prescribe anti-anxiety medications because they are addictive.

    My perception, and it could be wrong, is that this is especially true for those patients who have issues with psychosis. Ambien is often not prescribed to us, either. (Fine by me, Ambien is a weird drug, much weirder than any anti anxiety medication)...

    But back to the anti-anxiety bit. I knew, the first time I had a psychosis, and got over the initial trauma of the experience, what the triggers had been. Hormonal lack of sleep, compounded by unchecked anxiety.

    The first, old-schoold psychiatrists "got" that connection and gave me a script for anti-anxiety medications, PRN. Well, I didn't need them that much and needed them less and I stabilized. I am not an addictive sort of person.

    Some thirteen years later, I had a relapse, in prescription happy Georgia (influenced by a climate in which some Atlanta doctors made huge amounts of money on the edge of legality).. suddenly all we were given for psychosis was Depakote and Rerperdal.

    In the months following my recovery, I came to recognize my issue was anxiety, and again, lack of sleep around my period.

    My good doc nixed the Ambien script I got from a primary care doctor. He said it could precipitate psychosis. He also refused to give me an anti anxiety medication. Well, the sedatives I was on, I can assure you, were something one habituates to. The anxiety can still flare up. I needed something to use when I could not manage it myself.

    I replaced that psychiatrist, with the help of human angels who encouraged me to do so, when I was really not a good advocate for myself.

    To be continued.

  2. My new doc took me down off my heavy meds, but also gave me no tools to deal with what was now a PTSD response, from the fear of not getting good sleep. And fear of psychosis. It took me a second hospitalization for me to get my needs met. I was in a hospital where the psychiatrist consulted with me and listened to me. In that hospital setting, I got a whole arsenal of medications to take home, and my regular psychiatrist smiled at the collection. Interestingly I had managed to keep my antipsychotic medication from being increased in the hospital. I had the topmost dose of nasty Trazadone for sleep instead. It did not work well for me.

    I forgot to bring the anti anxiety medication with me, when I "showed off" my new medication regimen.

    I set off to wean myself almost as soon as I felt able. I started on the medication that my doctor would be least likely to object to: The Trazadone. And within six weeks I was completely off of it. Such a success I felt in being able to move in a positive direction.

    I would use that anti anxiety medication, clonopin, that was given me in hospital. I had actually been given it back in 1991, by the old-school docs, so I knew how it worked and I knew just having it in the medicine chest would help me to know I had a "friend" when I could not be a friend to myself, and ward off anxiety.

    After a year of using the 30 tablets, one-half at a time, i went into my psychiatrist, and brought my bottle to show him what I had been using in order to prevent hospitalizations. Clonopin. I showed him how I still had some tablets left.

    Ii had the proof I needed in order for him to prescribe me the medication I had needed. I could not be an addict and have the lowest dosage of clonopin last me nearly a year.

    That was how I got my script. I feel lucky. But many folks on public assistance, who could use an anti-anxiety medication PRN are still being told these drugs are dangerous, addictive, etc.

    How funny that my 30 tablets cost me a tiny tiny fraction of my current atypical antipsychotic. I am on the lowest dosage of that as well.... and take it at night....

    So, do you think there is any chance it really is an antipsychotic for me? Or do you think maybe I am just preventing a psychosis by getting good sleep?

    Just like our men in active duty in Afghanistan?

  3. I said, "One day I would share with you," and changed my mind. Obviously I got motivated last night and did it.

    I am a lot less scared of my story, my (mis) diagnosis and my prognosis these days.

    In large part because I believe those old tried and true drugs have their place in our current medication regimen. This clap trap about how much more effective the new meds are needs to be spoken. Thank you for doing so. I appreciate that the very drugs you were discussing are the ones that were withheld from me outside the "controlled" hospital setting.

    But I NEEDED them in my home so I could actually manage my own crises. You can tell me until I am blue in the face that Seroquel is an anti-psychotic. I am medication sensitive, so I know that even the mildest dose is more about sedation, and removing my ability to care, and my will. There is the slightest bit of anxiety quelling, but on a bad night when I need add a punch, I add the Clonopin. I can't believe that without proof that I was not addictive (I told the first doc I was not an addictive personality, but it got me nowhere)... I was not able to get a script for anti anxiety medications!

  4. I kind of like the conspiracy thinking. I've written somewhere before that big pharmas have to act like the corporations that they are, lest we forget that it's commerce, after all, that gave us dirt-cheap aspirin.

    1. RCHI,

      The post is actually more a criticism of the doctors who fall for this nonsense and should know better than it is of the drug companies. If the marketing tricks did not work, the companies wouldn't be using them.

  5. I do wish more doctors in private practice were independent thinkers.

    I tend not to want to be too into conspiracy thinking. I have noticed it feeds my "vulnerability." I've learned that paranoia is the result of using misperception of my self. In effect, conspiracy thinking is use a lens that should be retooled, because it's created a "lack of self trust" and allowing that lens to be used in looking away from myself, outwards, skewing my vision of the world.

    And thereby using my lack of self trust as a way of judging everyone else's motives.

    I learned this when I had a bad response to low blood sugar. I wondered, "why am I feeling paranoia, out of the blue. When I have had plenty of sleep? And once I fed myself, I could recognize the trigger in my thinking that had spiraled out of control. I could question how I was thinking about my SELF and the paranoia disappeared!

  6. I've been selling pharmaceuticals for the last decade and agree with Dr. Allen's assesment of Big Pharma's sleazy marketing techniques. Over the years I've witnessed reps promoting drugs off label, encouraging doctors to give medication coupons to their Medicare patients (who are not allowed to use coupons) and tell the patients to pay cash for the drug (Medicare fraud), significantly increase the prices of old brand-name drugs (Advair is now $350!), produce suspicious marketing literature that gets yanked by the FDA in six months, pay doctors $2,500 to give a one-hour presentation at a speaker program and put pressure on them to prescribe more of the company's drugs, etc.

    Doctors can also be guilty of participating in the sleaze--many physicians prescribe my drug off label, which they have the right to do. But I cannot discuss any off-label uses, and some customers push me to see if they can get off-label information (including clinical research in progress) out of me. I never give in, but it really bothers me that they don't respect the fact that I can only discuss approved indications.

    I sell a great drug now (reduces pain and has minimal adverse events) but it is a very old one that cannot be made into a bioequivalent generic, so the price just keeps going up and up. This is incredibly sleazy, too.