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.