FDA regulation, and off label use of atypical antipsychotic drugs

Abilify, Seroquel, Zyprexa, Risperal – these are among the atypical antipsychotics for which Americans paid $10 billion in 2008. $6 billion of that was for off-label use.

The FDA only approves drugs when their safety and efficacy have been tested for specific conditions. For example, an antipsychotic might be approved for the treatment of schizophrenia. When it’s prescribed for anxiety or depression, that’s an off-label use.

After heavily marketing off-label use, the makers of Zyprexa, Seroquel, and Abilify were fined a total of $2.3 billion for their defiance of FDA regulations. For the pharmaceutical industry these days, that’s just part of the cost of doing business.

This new generation of atypical antipsychotics is much more expensive than earlier drugs, which are now available as generics. According to a new study, they are not only more expensive. They are neither safer nor more effective than their predecessors, as initially assumed. Here’s what WebMD had to say:

“Atypical agents were once thought to be safer and possibly more effective,” says study researcher G. Caleb Alexander, MD, an assistant professor in the department of medicine at the University of Chicago Hospitals. “And what we’ve learned over time is that they are not safer, and in the settings where there’s the best scientific evidence, they are no more effective.” …

“Since there were all these new drugs, and it costs 700 to 800 million to bring a drug to market, drug companies needed to make that money back,” says Jeffrey Lieberman, MD, chairman of the department of psychiatry at Columbia University, who was not involved in the study. “These drugs were marketed aggressively.”

The study found that prescriptions for atypical antipsychotics have more than doubled since the mid-1990s, from 6.2 million in 1995 to 14.3 million by 2008. Atypicals are the top-selling category of pharmaceutical drugs. The growth is attributed to off-label use.

Over time, the way doctors prescribed those drugs changed, … with doctors becoming more likely to prescribe these powerful medications for conditions in which they had not been rigorously studied or FDA approved, such as anxiety, depression, attention deficit disorder, and for aggression and agitation in dementia patients. …

In children, the use of the drugs skyrocketed, increasing 800% from 1995 to 2005.

“Time and time again what we see is medications that are prematurely adopted in populations that have little or nothing to gain, and this study is yet another example of how both doctors and patients may overenthusiastically or prematurely adopt medicines beyond the evidence base,” Alexander says.

Can we change the future of medicine?

What does this study tell us about the practice of medicine, the pharmaceutical industry, and the eagerness with which patients medicate themselves, their children, and their elderly parents? That this is the future of medicine.

Could it be any different? What would it take?

Part of the problem comes from off-label use, but it’s difficult to stop pharmaceutical companies from promoting off-label use when the costs of the FDA’s fines are simply included in the pricing of the drugs. Doctors are very busy and rely on drug reps to keep them informed. It’s only natural for doctors to assume initially that a newer class of drugs will be safer and more effective than an older class. If that turns out not to be true, doctors aren’t going to hear about it from their drug reps.

The government could reconsider the appropriateness of direct-to-consumer advertising of prescription drugs. Should pharmaceuticals really be promoted in the same way as any other consumer product? The drug industry would argue that any restrictions on advertising violate free speech rights, just as the tobacco industry argues. The majority of the current Supreme Court would undoubtedly oppose any restrictions on the rights of corporations.

What needs to happen is for “consumers” of health care to take back their health and their lives. We are up against myriad financial interests that benefit from convincing us we’re not healthy enough. Our children may not have schizophrenia, but they might be at risk for it. Therefore we need more medical care and more pharmaceutical drugs.

Resistance to further medicalization will be an uphill struggle, but in the long run worth the effort.

Jan Henderson is a historian of medicine who blogs at The Health Culture.

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  • http://www.TheHealthCulture.com Jan Henderson

    Just read an interesting post today from someone inside the pharma industry: “What Is Really Killing Pharma” (http://bit.ly/eqmtF1) by Anthony Nicholls. He blames the importation of fancy marketing ideas by upper management, who interfered with the work of pharma scientists. “[A]s more and more of pharma’s budget was funneled into advertising and direct marketing to both the general public and to doctors themselves, the path to the top in pharma ceased to be via the lab bench and instead was by way of Madison Avenue.” A thought for today’s World Health Day, which highlights the lack of new antibiotics.

  • horseshrink

    Several years ago, a friend whose adolescent daughter spent much of her time on the horse show circuit was having problems with motivation and moodiness. She was home-schooled, but not diligent in her studies. Intense mom’s guiding discipline was erratic and loudly dramatic.

    Daughter spent much time on the couch, watching TV and IMing her friends, rather than poring over homework. She was moody in response to her mother.

    Off she goes to a psychiatrist. Can anybody guess the resulting diagnosis?

    You got it! Bipolar Disorder! (How’d you guess?)

    Meds prescribed, and an instant folie a quatre resulted.

    1. Doc believes in the diagnosis. He just got paid for it.
    2. Daughter believes in the diagnosis. It lets her off the hook.
    3. Mom is relieved. She can be angry at the diagnosis instead of her daughter.
    4. Drug company is happy. Their product is being purchased.

    Sad. Eventual actual diagnosis (besides normal adolescence and Type A mom) … muscular dystrophy.

    Psychiatrists have, in my opinion, become one-stringed guitars during their 15 minute superficial, widget processing appointments. One song … code a diagnosis/prescribe … code a diagnosis/prescribe … code a diagnosis/prescribe.

    When a new medication hits the market … O the joy! Something different to write on the Rx pad, and with cute drug reps to break the monotony!

    • http://www.TheHealthCulture.com Jan Henderson

      Horseshrink – Good analysis of who benefits. Sorry to hear about the MS.

      Just read a humorous/tongue-in-cheek post by a retired psychiatrist who asks if the pharma industry is promoting that mental illness be treated by PCPs rather than psychiatrists because PCPs will prescribe more. (The post is about paranoia.) http://bit.ly/f875kM

      • gzuckier

        Well, if the ED experience is any guide, yeah; first line treatment will be moved from extensive/expensive workups by a specialist to pharmacotherapy by a PCP.

  • http://www.zyprexa-victims.com Daniel Haszard

    Zyprexa,Risperdal and Seroquel same saga

    The use of powerful antipsychotic drugs has increased in children as young as three years old. Weight gain, increases in triglyceride levels and associated risks for diabetes and cardiovascular disease.
    The average weight gain (adults) over the 12 week study period was the highest for Zyprexa—17 pounds. You’d be hard pressed to gain that kind of weight sport-eating your way through the holidays.
    One in 145 adults died in clinical trials of those taking the antipsychotic drugs Zyprexa. This is Lilly’s # 1 product over $ 4 billion year sales,moreover Lilly also make billions on drugs that treat the diabetes often that has been caused by the zyprexa!

    Daniel Haszard Zyprexa victim activist and patient who got diabetes from it.

    • http://www.TheHealthCulture.com Jan Henderson

      Daniel – Very true about children. Sorry to hear about your experience. You might mind some encouragement for being an activist in this recent article by Ray Moynihan, called Power to the People. (http://bit.ly/fOvFEp) “The emergence of new citizens’ lobbies within healthcare, well versed in the way scientific evidence can be used and misused, may produce a more informed debate about spending priorities. Such citizens’ groups could routinely expose misleading marketing in the media and offer the public and policy makers realistic and sophisticated assessments of the risks, benefits, and costs of a much broader range of health strategies.”

  • Marc Gorayeb, MD

    Cynical post; cynical responses. In many cases, individual patients respond better to newly marketed drugs than to existing generics. In many cases. physicians prescribe or use medications for off-label purposes because they work.

    Furthermore, there is no reason to believe that our government cannot regulate direct-to-consumer advertising. Using the author’s own example, TV ads for cigarettes – by far the most potent way to market a product – are nonexistent, and I don’t see anyone rushing to the “current Supreme Court” to strike down those regulations. Direct-to-consumer TV ads for pharmaceuticals can most certainly be regulated. Look to your politicians for the reasons why they are not.

    • http://www.TheHealthCulture.com Jan Henderson

      From biophysicist Anthony Nicholls: What Is Really Killing Pharma (http://bit.ly/eqmtF1) “I have come to believe (and I admit that this is only a theory) that as more and more of pharma’s budget was funneled into advertising and direct marketing to both the general public and to doctors themselves, the path to the top in pharma ceased to be via the lab bench and instead was by way of Madison Avenue. … One consequence of this shift from science to business in the pharma industry has been less and less appreciation for the realities—as opposed to the hype and hope—of drug discovery. This is reflected both in the quixotic choices made by pharma as to what to pursue and in the stunningly bad management of the core talent in drug discovery.”

  • http://www.drjoe.net.au Dr Joe

    Medicalizng human behavior is big and profitable business. Why is it always assumed that a new drug must be better? Marketing may have something to do with it. That may be why the marketing budget of big pharma can exceed the R and D budget.

    • http://www.TheHealthCulture.com Jan Henderson

      Dr. Joe – At least there are more voices speaking out about medicalization these days, and not only with regard to behavior. It used to be just journalists like Lynn Payer (who is no longer alive) and Ray Moynihan. Now it’s MDs like H. Gilbert Welch and Carl Elliott.

  • Mickey

    My son has been on the lowest dose of Zyprexa & Zoloft for 10 years now because he has Psychotic breakdowns. This began at age 19 & even under a Pshyciatrists care doesn’t seem to be getting any better. He doesn’t want to increase the dosage because of the side effects. He also does not want to take other medications. What is the alternative?

    • http://www.TheHealthCulture.com Jan Henderson

      I’m sorry to hear about your son, Mickey. It must be a very difficult time for both of you. I believe it’s the policy at KevinMD not to offer any medical advice. You might try the resources of the National Alliance on Mental Illness (http://www.nami.org/). Their website lists local chapters where you might find both support and suggestions for alternatives.

  • gzuckier

    “Doctors are very busy and rely on drug reps to keep them informed. It’s only natural for doctors to assume initially that a newer class of drugs will be safer and more effective than an older class.”
    yeah, for graduates of the Turnip Truck School of Medicine.

    • http://www.TheHealthCulture.com Jan Henderson

      That’s a good point. Doctors are smart enough to know better, especially with all the publicity about the nefarious behavior of Pharma. But how much prescribing of the most recent drugs is driven by patients asking for what they’ve seen advertised in a visually enticing and manipulative format? Being smart is a poor defense against a patient who has become a consumer, over-educated by the media.

  • http://www.trialx.com/curetalk Kimberly Blozie

    GREAT blog!

    My two points in response (which I’ve summarized in a blog of my own – http://trialx.com/curetalk/2011/04/drug-patents-lawsuits-future-of-medicine/) are:

    1) Don’t get me wrong, big pharma does a lot of good, but when drug patents expire, lawsuits typically follow. This is a very sneaky way for pharmaceutical companies to maintain revenue streams.

    2) I agree, the people ultimately create the demand. The onus is on us. We need to realize that because we are born we are not entitled to feeling high all the time. What about living for something deeper than how we feel?

    • http://www.TheHealthCulture.com Jan Henderson

      Kimberly – Thanks for your post with the link back to here. Nice blog.

      The role of patients is complex and interesting. The public doesn’t create that demand out of thin air. We’re taught to seek more medical care and to expect pharmaceutical treatment.

      People used to see a doctor when they were sick. Now the medical industry knows how to create patients. It looks for abnormalities with an ever finer grain and can usually find something for the patient to worry about. It’s not easy for individuals to resist a logic that tells them more medical care is what they need to be healthy. But the overtreatment of those who are not sick but merely at risk can do more harm than good.

      A few individuals speak out on this issue: H Gilbert Welch (http://amzn.to/gkHtfk), Shannon Brownlee (http://amzn.to/fjpokk), John Abramson (http://amzn.to/e58VBw), Nortin Hadler (http://amzn.to/h23jXp). To your point about what we should be living for, Welch says: “there is more to being healthy than striving to avoid death and disease. Health is more than a physical state of being; it’s also a state of mind.”

    • http://www.TheHealthCulture.com Jan Henderson

      I forgot one other excellent book on this theme: The Treatment Trap: How the overuse of medical care is wrecking your health and what you can do to prevent it, by Rosemary Gibson of the Robert Wood Johnson Foundation and Janardan Prasad Singh, economist at the world bank (http://amzn.to/fIj9b3). It’s not just journalists who are presenting this argument.

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