Psychiatry’s Over Reliance On Pharma

I recently read The NIMH-CATIE Schizophrenia Study: What Did We Learn? by Jeffrey Lieberman, MD, and T. Scott Stroup, MD, MPH.  The article was published in the American Journal of Psychiatry 168:8, August 2011.  

Here are two quotes:

“When the CATIE study was designed in 1999-2000, the prevailing opinion of researchers and clinicians alike was that the newer (second-generation) antipsychotic drugs were vastly superior to the older (first-generation) antipsychotic drugs in efficacy and safety. This largely reflected the results of studies sponsored by the manufacturers of the new drugs…, marketing messages of pharmaceutical companies and the hopes of many who wanted better treatments.”

“CATIE helped to demonstrate that, although the introduction of second-generation antipsychotic drugs brought new options for treatment of psychosis, the major advance many had hoped for remains elusive.”

Let’s take a look at the first passage.  Essentially what’s being said is that by about the year 2000, psychiatric researchers and practitioners believed that the second-generation neuroleptics were vastly superior to the older drugs in effectiveness and safety.

The CATIE study debunked these beliefs, as is acknowledged clearly in the second quote.

EFFECTIVENESS AND SAFETY

Here is a list of the second-generation neuroleptics introduced prior to the year 2000 with the main adverse effects associated with the use of each drug as listed in the 2001 PDR.

  • Clozapine, Clozaril (1989).  Adverse effects:  agranulocytosis (black box); seizures (black box); orthostatic hypotension (black box); neuroleptic malignant syndrome; tardive dyskinesia; akathisia, etc… 
  • Risperidone, Risperdol (1994).  Adverse effects:  extrapyramidal disorders; akathisia; aggressive reaction; joint pain; weight gain, etc… 
  • Olanzapine, Zyprexa (1996).  Adverse effects:  neuroleptic malignant syndrome; tardive dyskinesia; akathisia; weight gain; postural hypotension; joint pain; extremity pain, etc… 
  • Quetiapine, Seroquel (1997).  Adverse effects:  neuroleptic malignant syndrome; tardive dyskinesia; orthostatic hypotension; seizures; hypothyroidism; cholesterol and triglyceride elevations; etc… 

Each entry in the PDR is a verbatim copy of the manufacturer’s FDA-approved labeling information and is updated annually.  It is clear, from the adverse effects listed with each of these products, that the respective manufacturer acknowledged clearly that there was a real danger of serious and potentially irreversible adverse effects.

With the exception of clozapine, the manufacturers also acknowledged that their efficacy data was based on very short-term trials.

  • risperidone                  3 weeks
  • olanzapine                   6 weeks
  • quetiapine                    6 weeks 

The entry for olanzapine (Zyprexa) stated explicitly:

“The efficacy of ZYPREXA was established in short-term (6-week) controlled trials of schizophrenic inpatients…

The effectiveness of ZYPREXA in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials.  Therefore, the physician who elects to use ZYPREZA for extended periods should periodically re-evaluate the long-term usefulness of the drug for this individual patient… [emphasis added]

ZYPREXA is indicated for the short-term treatment of acute manic episodes associated with Bipolar I Disorder.

The efficacy of ZYPREXA was established in two placebo –controlled trials (one 3-week and one 4-week), with patients meeting DSM-IV criteria for Bipolar I Disorder who currently displayed an acute manic or mixed episode with or, without psychotic features…

The effectiveness of ZYPREXA for longer-term use, that is, for more than 4 weeks treatment of an acute episode, and for prophylactic use in mania, has not been systematically evaluated in controlled clinical trials. Therefore, physicians who elect to use ZYPREXA for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient…” [emphasis added]

Against this background, it’s difficult to afford much credence to the assertion of Drs. Lieberman and Stroup that the responsibility for psychiatrists’ false beliefs that these products were vastly superior to the old drugs in efficacy and safety can be laid at the feet of pharma.

It is noteworthy that Drs. Lieberman and Stroup mention not only industry sponsored studies, but also pharma’s “marketing messages.” [emphasis added]

This strikes me as an extraordinary admission.  America is the birthplace of aggressive marketing, and we all know how successful it can be in the selling of cars, vacuum cleaners, etc…  But for a group of people, who routinely claim that they are a bona fide medical profession, to admit that they were duped by tawdry marketing ploys raises serious concerns about their credibility and competence.

Drs. Lieberman and Stroup are defending psychiatry’s overly zealous adoption of the newer drugs by blaming the pharmaceutical companies’ misleading research and commercials.  But the much more fundamental issue is:  why did psychiatrists believe these messages despite the fact that the PDR entries for the drugs in question provided abundant justification for caution and restraint?

It’s difficult to avoid the suspicion that the various largesse showered on psychiatry by the pharma industry might have played some part.

It’s also clear that psychiatrists’ love affair with these drugs and their vulnerability to pharma marketing continue to this day.

In the third quarter of 2013, the second-generation neuroleptic Abilify (aripiprazole), with over $1.5 billion in sales, was not only the best selling neuroleptic drug in the US, it was the highest grossing of all prescription drugs.  It was also the most heavily promoted neuroleptic in 2011 (the last year for which I can find data), and accounted for 38% of neuroleptic promotional spending.

However, there is nothing in the current PDR entry, which is available online, to suggest that it is any safer than the other products.  All the usual second-generation neuroleptic adverse effects are listed, including tardive dyskinesia, akathisia, weight gain, metabolic problems, neuroleptic malignant syndrome, etc…  There are also two black box warnings:  increased mortality in dementia-related psychosis; and increased suicide risk in children and young adults.

In addition, efficacy studies were limited to 6 weeks.

SUMMARY

So in 2011, we had Drs. Lieberman and Stroup blaming pharma advertizing for psychiatry’s misplaced enthusiasm for the newer neuroleptics, while side-stepping the obvious corollary:  that psychiatrists were taken in by these promotions.  Now, two years later, the problem is still with us.  Psychiatrists apparently are still responding positively to the marketing messages; and neuroleptic drugs, which in former times were barely a blip on the sales charts, are now acquiring blockbuster status.

  • Bernard Carroll

    Driving the increasing sales numbers is use of these neuroleptic drugs by primary care providers over and above their use by psychiatrists. PhRMA has aggressively
    promoted symptom-driven off label use and new indications for anxiety, insomnia, depression, agitation, hostility. The stealth message is that these drugs are broad spectrum psychotropic agents – good for most of what ails you.

    I have tried to push back especially against their oversold use in depression –
    see http://www.ncbi.nlm.nih.gov/pubmed/20123926
    and http://www.ncbi.nlm.nih.gov/pubmed/19142117
    and http://www.ncbi.nlm.nih.gov/pubmed/18033236

  • Francesca Allan

    Lieberman’s contortions no longer surprise me. Generally, psychiatrists (especially researchers) seem unable to take responsibility — everything must be somebody else’s fault because psychiatrists are blameless and do brave and holy work. If a patient doesn’t respond, then that’s because they’re treatment-resistant or not trying hard enough. But if a patient does respond, then they’ll take the credit for that.

    Looking at the list of atypicals was like a trip down memory lane. At one point I was on at least 2 of them in addition to mood stabilizers and benzodiazepines. I was drugged into oblivion. I ate a bar of soap thinking it was an apple. I couldn’t remember my phone number.

    I am currently being prescribed Risperdal which I dumped due to intolerable hormonal side effects. My psychiatrist mentioned a new, improved atypical antipsychotic. I can’t remember the name but I do recall saying “And, no doubt, it’s more expensive” which he couldn’t deny. We don’t pay for our drugs in Canada but that’s not the point.

  • mjhoward

    Let the buyer beware should be printed on the package insert of
    every psychotic drug when it’s dispensed.
    Lieberman has acquired the necessary skills to achieve stardom in the
    pharma world when it comes to disseminating the corrupt data of most of the
    clinical trials for the atypical drugs.
    He’s become the master of publishing an article that is carefully
    crafted to draw attention away from any of the drugs known liabilities, and
    deft at the use of deception when it comes to exposing any real efficacy. He gives credence to the term “Quack.” I remember the first publication that came out regarding the CAFE’ study ” Landmark Study” was how it was titled, and of course AstraZenca touted it as the next coming of the Holy Bible. Well, we all know how that turned out, and of interest the rate of Akathisia was about 20% across the board in the study, with a dropout rate of 70%. My idea of what a “Landmark” study would be and Lieberman’s are polar opposites. Actually, I think the term prostitute fits him quite well.

  • emma friedmann

    So how does the world improve medicine regulation? Check out the #AllTrials campaign

  • Phil_Hickey

    mjhoward,

    Yes; his credibility sinks by the day!

  • Phil_Hickey

    Emma,

    Thanks for coming in. At the present time, in my view, psychiatric research is little more than marketing, with all the hyperbole and deception that the term implies. All trials registered – all trials reported – would certainly be a step forward, but my guess is that pharma is already working out ways to get around it.

  • Bernard Carroll

    It is best not to conflate psychiatric research with clinical trials. Those are just a part of psychiatric research. A broad look across the many journals will confirm that. Beginning in around 1990 I began to observe the clinical trials tail wagging the clinical research dog, to the detriment of both. Interesting and important clinical research questions became
    neglected while we saw the rise of boring and trivial marketing exercises that I labeled experimercials. See http://tinyurl.com/mwghood

  • Phil_Hickey

    Dr. Carroll,

    That’s a good point. Not all research studies focus on simplistic measures of outcome.

    Nice article! Thanks for the link.

  • cannotsay

    As Thomas Szasz said, things like “the chemical imbalance” are stories, fables that psychiatrists tell their patients to fool them into drugs. I have known my share of people who hold different kinds of beliefs, many very strange. I am not talking about beliefs that are accepted as mainstream (such as religion, even though atheists have a problem with that) but things like the 2012 doomsday prediction or people who genuinely and positively “believe” that astrology and homeopathy are scientifically valid fields. Emphasis on “believe”.

    So I do not underestimate the fact that there certainly is a sizable part of the public who is vulnerable to any kind of marketing agenda uttered by a guy who wears a white coat and who says “I have an MD degree, trust me”. The average person is scientifically illiterate and can be fooled to believe anything to be scientific even if it is not.

    You can picture the situation in my own case. The two psychiatrists who held the keys to my freedom during my ordeal in Europe had good “medical training” by that country’s standards, but certainly not the type of Ivy League scientific education that I had had in the United States. Yet, I had to “make it look like” that I believed their fairy tales of “chemical imbalances” that they were telling me if I had any hope of escaping :D.

    It was a pure Rosenhan experience: I had to agree to the view that two dumb people (their IQs were objectively lower than mine) had of me, if I held any hope of getting out of there!

  • Aria

    Ah, Mistress Seroquel and Sir Zyprexa… thank you for the Tardive Dyskinesia, blurred vision, incontinence, cholesterol and triglyceride elevations; etc…

    I ended up with Seroquel Induced Acute Pancreatitis and spend some time in the ICU. Later I asked my prescribing psychiatrist why he hadn’t had my blood levels done and he blanched. He’d been too busy prescribing without doing the necessary workups. If he’s using MD after his name then he needs to act like one.

    I’m thoroughly enjoying your blog””