NIMH Delivers a Kill shot to DSM-5

Science.Com
By Hank Campbell
May 3rd 2013

( NIMH is replacing the DSM http://www.nimh.nih.gov/research-funding/rdoc/index.shtml )

The National Institute of Mental Health (NIMH) is distancing itself from the the American Psychiatric Association and its upcoming Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

While they acknowledge that the goal of DSM "is to provide a common language for describing psychopathology" they are no longer convinced that approach has value if we are going to solve 21st century neuroscience problems.  It is, paraphrasing the statement  of Thomas R. Insel, M.D., Director of the National Institute of Mental Health, more of a dictionary than a manual.  He uses the term "Bible" instead of 'manual' but I would have used 'glossary' rather than 'dictionary'.

Insel pulls no punches in his statement on why they are not going to fund things based on DSM criteria any more.

"The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure."

This is a charge leveled at psychology as well, and the field in general, but psychiatry takes the biggest hits, because they are supposed to be the most evidence-based. Unlike psychology, psychiatrists have to be M.D.s first. Writing in The New Yorker, Gary Greenberg tries to tackle why neuroscience hasn't kept pace with medicine, much less science, writing rather nicely that "it’s not entirely clear that psychiatrists want a solution to the problem."

Insel is more blunt. "DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever."

Basically, he says DSM is stuck in the past.

Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.

Patients with mental disorders deserve better.

NIMH is leaving the past behind. In the past, Insel notes, they would reject a biomarker that did not match a DSM category. Now they instead want to collect how all data - genetic, imaging, physiologic and cognitive - cluster, and not just how symptoms do.  They call it the Research Domain Criteria (RDoC) project.

"That is why NIMH will be re-orienting its research away from DSM categories.," he wrote, and that means funding applicants are going to have to adjust to the 21st century.

The APA may be outraged, and certainly some DSM defenders, but I predict people in neuroscience who want to really do science and get NIMH funding are relieved that they are not going to have to cater to a document everyone seems to know was always flawed.

Psychiatric Profession Has Lost Its Mind

Psychiatric Profession Has Lost Its Mind
April 17, 2013  
American Free Press

Nearly every expression of normal emotion can now be classified as a syndrome in need of medication

By Pete Papaherakles

In May 2013, the American Psychiatric Association (APA) is scheduled to release its fifth Diagnostic Manual of Mental Disorders (DSM-5) superseding the DSM-IV published in 1994 and revised in 2000. The new “psychiatry bible” has been criticized by many as a testament to the insanity of the industry itself. Virtually every emotion experienced by a human being—sadness, grief, anxiety, frustration, impatience, excitement—is now being classified as a “mental disorder” demanding chemical treatment with—you guessed it—pharmaceutical drugs.

Ironically, one of its harshest critics is Allen Frances M.D., professor emeritus from the Department of Psychiatry at Duke University who was chair of the DSM-IV Task Force.

“DSM-5 opens up the possibility that millions and millions of people currently considered normal will be diagnosed as having a mental disorder and will receive medication and stigma that they don’t need,” said Frances. “This is the saddest moment in my 45-year career of studying, practicing, and teaching psychiatry. [The] approval makes it likely that DSM-5 will start a . . . dozen or more new fads which will be detrimental to the misdiagnosed individuals and costly to our society.”

The DSM is now larger than ever, and it includes Orwellian disorders such as “obedience defiance disorder” (ODD), defined as refusing to follow authority. Rapists who feel sexual arousal during their raping activities are given the excuse that they have “paraphilic coercive disorder” (PCD) and therefore are not responsible for their actions. You can also get diagnosed with “hoarding disorder” if you happen to stockpile food, water and ammunition, among other things. Being prepared for possible natural disasters now makes you a mental patient in the eyes of modern psychiatry.

The entire industry of psychiatry has become such a laughing stock that even many supporters of the industry are turning their backs in disgust. To many scientists today, psychiatry is no more “scientific” than astrology or palm reading, yet its practitioners call themselves “doctors” of psychiatry in order to sound credible.

The authenticity of already established “disorders” such as attention deficit hyper-active disorder (ADHD) and social anxiety disorder (SAD) have been called into question.

Frances admits that even the 1994 DSM-IV was a huge mistake that has resulted in the mass over-diagnosis of people who are actually normal.

The major victor in this is the pharmaceutical industry, which is having a field day with sales of billions of dollars of psychotropic drugs such as Prozac, Ritalin, Zoloft, Paxil and others.

Since the introduction of Prozac in 1987 there has been an explosion in the number of people using psychiatric drugs. One in five Americans, or 65M people, is now taking at least one psychiatric drug such as anti-depressants, anti-psychotics and anti-anxiety medications, according to an analysis of pharmacy claims data released on November 2011. In 2010, Americans spent $16.1B on anti-psychotics to treat depression, bipolar disorder and schizophrenia, $11.6B on anti-depressants and $7.2B on treatment for ADHD, according to IMS Health, which tracks prescription drug sales. The report showed that, between 2010 and 2011, the use of psychiatric drugs had increased a staggering 21%.

The adverse effects from these drugs are devastating. Over 200K people a year in the United States enter a hospital with anti-depressant-associated mania or psychosis. There have been 66 school shootings and over 1,300 murders and suicides by psych-drug users since 2000. The Columbine, Virginia Tech, Red Lake Reservation and Northern Illinois University shootings were all committed by individuals on psych drugs, as were many other mass shootings. At least 5K other news stories, including school shootings, link psychiatric drugs to violent crime, according to the website “SSRI Stories,” which tracks these cases.

Peter Papaherakles, a U.S. citizen since 1986, was born in Greece. He is AFP’s outreach director. If you would like to see AFP speakers at your rally, contact Pete at 202-544-5977.

Amazing Dr. Allen Frances Interview Exposing DSM5

Transcript: Problems With Psychiatry's DSM-5; A Conversation with Allen Frances, M.D.,

Allen Frances interview recorded Nov 10, 2012

By Rob Kall

Rob: "Radio ID" My guest tonight is Allen Frances, M.D.  He was the chair of the DSM 4 Task Force and the chair of the department of psychiatry at Duke University School of Medicine, Durham, North Carolina.  He's currently Professor Emeritus at Duke.  Welcome to the Show!

Allen: It's good to be here.

Rob: Now, the reason I contacted you is you wrote an article titled "DSM 5 Field Trials Discredit the American Psychiatric Association."  Why don't you start off by explaining what DSM 4 and DSM 5 are and what they mean and why they are important?

Allen: This is the diagnostic manual in psychiatry.  Until 1980, no one much cared about it, but DSM 3, published in 1980, became a huge best seller.  There are hundreds of thousands of copies sold every year, and the reason it is so important is because lots of decisions depend on it-- who gets treated and who doesn't, who pays for the treatment, who gets disability, who gets to pilot a plane, who gets to adopt a kid, workman's compensation.  All sorts of things are triggered -- and school services in particular -- on having a psychiatric diagnosis.  It essentially sets the boundary between who's normal and who's not.  So this has become an enormously important document.  The last version of it, which I was sort of the head person on, was published in 1994, and there is a revision that is about to appear next year; it's called DSM 5, and that revision has been very controversial- I guess for reasons that we will discuss.  But the changes made there could determine how tens of millions of people regard themselves: whether they have a mental disorder or not, and it could determine who gets medication and lots of people in our society are getting medication they probably don't need; so the stakes are pretty high. 

Rob:   As the Director of Development of DSM 4- I may not have that title exactly right; correct me if need be- you had to be pretty high in terms of being a trusted member of this psychiatric hierarchy.  How did that happen?  How did you get that position?

Allen:   I worked on DSM 3, and I was part of the group that prepared DSM 3R- that was a revision in 1987- and so I had some experience in the kinds of questions involved.  It's a pretty tedious job; I'm not sure that many people in the world would have wanted to do it.  So, yes, I was involved very much in how psychiatric diagnosis would evolve, and I guess what has happened in the last three years is I have become a critic of that process.  So, I went from being the director of a program that was involved in preparing DSM 4 to being a very sort-of staunch critic of how DSM 5 is being prepared.  I don't think that the process has been careful enough or open enough to produce a document that will be trustworthy. 

Rob:  You describe how it affects people's lives, but it also affects business too- the pharmaceutical business.  How many billions of dollars will be relying on DSM 5?

Allen: It's really weird- the degree to which Americans are taking psychotropic medications.  In any given year, 20 % of Americans will take a drug that is a psychiatric drug.  About 11 % of the population is on anti-depressants, and 20 % of women are on anti-depressants, 4% of kids are on a stimulant, 4% of teenagers are on an anti-depressant.  Perhaps most remarkably, anti-psychotic drugs are amongst the best selling drugs in America: 18 billion dollars a year in anti-psychotic drugs, anti-depressants about 12 billion dollars a year, stimulant drugs about 7 billion dollars a year.  So we've really become a pill popping culture and the drug companies have a huge stake in this.  We are the only country in the world now that allows drug companies to advertise directly to consumers.  So, you are constantly seeing ads on TV, trying to disease-monger; trying to suggest that you have one or another psychiatric disorder, that this is a chemical imbalance in your brain, that if you take a pill that will be the solution to all of life's ills.  And the drug companies have essentially gone into the business of selling psychiatric diagnosis as a way of selling pills.  If they can convince enough people that they are sick, then if people ask their doctor for a pill, they are very likely to get it.  If you ask your doctor for a psychotropic medication, you're 17 times more likely to walk out of the office with a pill.  The real problem here is that most of these pills are not being prescribed with psychiatrists and aren't being done after careful diagnostic interviews with someone who knows something about psychiatric diagnosis.  About 80 % of psychotropic drugs in America are prescribed by primary care doctors who have -- in most instances- very little time- the average visit is about 7 minutes- in many instances little or no training in psychiatry, some instances no interest in psychiatry.  And primary care doctors tend to be inordinately influenced by drug sales people.  They get their education in psychiatry from people who are selling drugs who have the story line that psychiatric diagnosis is often missed, is very easy to make, and that there is a simple pill that will solve all the problems.  So the current situation is weird; we have 90% of anti-anxiety drugs like Xanex being prescribed by primary care doctors, and 80% of anti-depressants are prescribed by primary care doctors.  60% of stimulants and half of the anti-psychotics are being prescribed by primary care doctors, very often after these brief seven minute interviews, very often because the doctor has samples that he has been given by the drug salesman that he gives out.  This is a convenient way to get the patient out of the office quickly.  And, the result is a tremendous overdose, I think -- societal overdose- of medication.  7% of the population is addicted to a prescription drug- 7%.

Rob:   How many?

Allen:   7% of the population

Rob: 7%

Allen: 7, yes.  And it turns out that there are now more visits to the emergency room for overdoses with prescription drugs than visits with street drugs.  In some ways, we have turned a very bad corner where the drugs you get from the doctor can cause you more harm than the drugs you would get from a street corner pusher.  So, I think that there has been a kind of overdose of diagnosis and overdose of medication.  And part of my reaction to DSM 5 is that it will make this worse by introducing new diagnoses that will have many millions of people qualifying for a mental disorder who --the night before it is published- would not have been considered to have a psychiatric illness.  And it's reducing some of the thresholds for existing disorders, which again will increase diagnostic inflation and make it more likely that people will get psychotropic medication that they don't really need plus the stigma of having a diagnosis that you don't really have.

Rob:   This is huge for big Pharma, right?

Allen:   Oh yeah.  And let me be clear; big Pharma has absolutely no influence on what's happening.  So the people preparing DSM 5 are not doing this with the intention of helping the pharmaceutical industry.  They are not doing this because of financial conflict of interest.  They are doing this- I think they are making a lot of very bad decisions, but the decisions are being made for the purest of motives.  However, Pharma will be on the sidelines licking their chops and figuring out how to exploit it. 

Rob: Why do you think this is happening then, because obviously you believe that this is a terrible error or not maybe error because it is intentional?  They are making judgment calls that are really bad you are pretty much saying.

Allen:  Yeah, I think that they are making very bad decisions for the purest of reasons.  The conflict of interest is not financial; it's more intellectual, and there are two parts to it.  One is, if you are an expert working in a field, you tend to develop a huge attachment to your field.  You always worry about the fact that you may miss a patient that has a diagnosis in the area of interest that you have.  So you worry very much about expanding the domain of your area of research and clinical interest.  Experts never think about the impact of people who are mislabeled; they always worry about the people who are missed.  And, they tend to overvalue their own research and their own area of interest.  I think that is a big part of it. 

Rob:  You've written about your concerns about the research and then the quality standards.  This is not about concerns is it?  Is that the same issue?

Allen:  I think that very often the experts are suggesting diagnoses that are based on their own research or research of colleagues that is very far inadequate of proving that the suggestion is safe and scientifically sound.  Normally, there will be a study that shows there are some people who have a problem that can't be diagnosed using the current system, and this will be argued in support of evidence for adding a new diagnosis or reducing the threshold of the existing one.  But the thing that is always missing in these calculations is a thorough risk benefit analysis: thinking through all the things that can go wrong for the people who are mislabeled.  Every time you make it easier to get a diagnosis, you will pick up people who previously were missed, but you will also pick up a bunch of people who don't really need the label.  And experts have a vested interest in worrying about the missed patients; they have much less concern about the mislabeled patient.  The other thing here is really interesting, and it goes to a much larger question in American medicine, not just psychiatry: there has been- in the past thirty years- a tendency to think that we can do a kind of preventive medicine with very early screening tests for a number of diseases.  And if we could get there early enough, if we could  make the diagnosis early enough and begin the treatment before the disease could develop and do its worst harm- that this would be in the long run what benefits the patient.  What's happening now, just in the last couple of years, is the realization that we are doing way too much screening in medicine and way to much preventative medicine.  Very often, you will see that the effect of early diagnosis is to provide treatment and to do tests that are more dangerous than the disease itself would have been.  So this is really a kind of sudden shift away from the notion that we can screen for every illness and get there early to a realization that this early screening may not have improved outcomes and may have caused harm because the treatments and the tests can be so harmful.  So, recently, there is an initiative called Choosing Wisely, developed by eight of the different medical specialties saying, if effect, let's pull back.  Prostate screening was all the rage; now the recommendation is don't screen for prostate- that by and large it doesn't save lives and it causes a tremendous amount of damage and unnecessary surgery- that the prostate cancers that were picked up very often wouldn't kill the person, but the treatments can be very harmful to them.  Breast cancer screening has turned out to be way overdone, and it is important to begin targeting it to particular age groups and to do it less frequently.  And, actually, they have identified about 46 different areas in medicine where there has been too much testing and treatment.  Well, psychiatry is getting into this act late in the day at just the wrong time and with the best of intentions but probably the worst of unintended consequences.  The idea in DSM 5 was, if the rest of medicine is screening early; why shouldn't we?  And so a number of the different suggestions are for disorders that are much milder than the traditional psychiatric disorders-intending to pick up earlier in the course the sorts of problems that might develop into schizophrenia or dementia, and hoping that you could intervene early before the disease has fully announced itself and caused its damage.  But, in order to have a screening test-or a screening diagnosis that is useful- you have to prove three things.  One, that it is going to be accurate- if you are going to introduce a new diagnosis, you want it to be accurate.  The second is intervention that will be really effective for it.  It doesn't make sense to be identifying something if you can't do something about it.  And, the third is intervention will be healthful and not harmful- that it won't cause more side effects and more complications than whatever benefit it will provide.  It turns out, for all of the suggestions being made in DSM 5, there is no way of making the diagnosis accurately for just the people who need it-that there will be what we call a huge false positive rate- that in order to pick out the person who might go on to have the problem, you'll often be picking up maybe eight or nine people who wouldn't.  And, the intervention for them and the stigma for them is unwarranted.  There is really no excuse for mislabeling someone and possibly giving him a treatment that is going to be harmful, or to a label itself that may be stigmatizing.  The second issue is that for none of the things being suggested in DSM 5 is there a proven effective intervention.  And, the third thing is-as we were discussing before- very often the reflex, especially in the United States, when there is a diagnosis of a mental disorder, is to go right ahead and provide a medication- particularly since so much of the diagnosis and treatment is being done by primary care doctors in the seven minute appointments influenced so much as they are by the drug company sales people.  So, for the new diagnoses being suggested in DSM 5, very often there is a risk --a high risk- that it is inappropriate.  There is no proof at all that the diagnosis will be helpful, because none of the diagnoses have an intervention that has been proven affective.  And, in many instances, a person may get medication that will be harmful as well as a harmful stigma.  So, my contention is that we shouldn't be venturing into the area of preventive psychiatry just at a time when preventive medicine is coming under such criticism and scrutiny because it is premature.  In psychiatry, we certainly don't have the tools for an accurate diagnosis before the illness has declared itself.  We don't have interventions that have been proven to be helpful.  And, the interventions that are likely to occur might actually be quite harmful. 

Rob:   "Station ID" My guest tonight is Dr. Allen Francis.  He was the chair of the DSM 4 task force and the department of psychiatry at Duke University, and he has become a very strong critic DSM 5, which is soon to be released upon the public.  Just to sum up a bit: you said that the new DSM 5, which is the official diagnostic standard for all kinds of psychiatric problems, is going to create problems, because there are going to be a lot of people who are false positives-  Many, many times more who are false positives than are really diagnosable.  And, then you said that there is a medication response- specifically in the United States- where the tendency is if somebody meets the criteria that somebody reads in this, they are going to be put on psychiatric medications.  So, a couple of questions: What is the percentage of people who are currently diagnosed and medicated with psychiatric medications in the United States? How does that compare with other countries?  How do you think that will change with DSM 5? There you go- that is a couple for starters.

Allen: Good summary and good questions.  Currently, 20% of the population in any given year will have a psychiatric diagnosis-20%.  Of that 20%, only a quarter- so 5% of the whole population- have a severe psychiatric disorder.  15% would have a mild to moderate one.  Lifetime- the rate would be 50%.  And, the scary thing is that these may actually be underestimates, that if you carefully do prospective interviewing, it turns out that by age 32, half the population would qualify for an anxiety disorder, 40% for a mood disorder, 30% for a substance disorder.  So, we have a situation in which a very large proportion of the population would qualify for a psychiatric disorder.  Europe is catching up; there is a lifetime rate of about 43%.  And, a really scary study recently showed that if you evaluate kids carefully, by age twenty one 83% of kids would qualify for a mental disorder. 

Rob: 83% of kids would qualify for medication?

Allen: No, for a mental disorder.

Rob: Oh, for a mental disorder.

Allen: And, so in other words, if you do careful follow-ups -- you start taking a population of kids, a general population of kids and you follow them- randomly selected- for eight years- age 12 until 21- and you do careful interviews, you get a tremendously high rate of disorder.  Now, I think these are exaggerated numbers.  I think that the way that the disorders are defined are too loose and the way the studies are done tends to have a biased toward reporting high numbers.  But, I think that the problem- by the way, Rob?

Rob: Yes?

Allen: I think the battery in my phone might go out.  If it does, I'll recall on another phone. 

Rob: I'll hang in there and you call right back to the same number.

Allen:  Yes, that would be good.  I think that the issue here that we have a diagnostic system that encourages very high rates of diagnosis.  And, we have a capitalist system of medical care that encourages drug companies to take full advantage of these high rates of diagnosis: to encourage very loose and inappropriate diagnosis and the resulting excessive treatment with potentially very harmful medications.

Rob: Now, from what you've described at the beginning of the interview, where most of the psychiatric medications are prescribed by general practitioners and not psychiatrists, this can't be very good for the field of psychiatry in terms of their making a living and the job being done properly.  What do you have to say about that?

Allen:   I don't think the living issue is really pertinent, because psychiatrists are busy enough.  I think that it's not like they need more business.  I think it is a terrible problem in terms of shoddy diagnostic and loose prescription habits reigning so supreme over good diagnostic practice.  It takes a long time really knowing someone to make an accurate psychiatric diagnosis.  It requires someone who has substantial training; especially when the diagnosis is of a mild condition that is on the fuzzy boundary with normality.  If someone has a clear cut psychiatric problem, almost anyone can make the diagnosis, but the people being diagnosed in primary care often present at the boundary with normality.  Here diagnosis is extremely difficult.  It often requires great expertise on the part of the person doing it and often takes lots of time- both in the individual interview and following people over time- not jumping to a diagnosis.  We have another problem in America that [?unclear 21:26] you don't necessarily have to have a diagnosis to get treatment.  But, our insurance systems were such that unless you get diagnosed early, the doctor won't be paid for the treatment.  There is tremendous pressure, therefore, for people to be fit into categories well before anyone can be sure that they really need the diagnosis.  Most of life's problems are not mental disorders and we have tremendous resilience as human beings.  Most people with a psychiatric symptom don't have a psychiatric disorder: it is not severe enough, it is not prolonged enough.  But very often, there is a quick jump to making a diagnosis before one is needed.  And watchful waiting, for most people with mild problems, watchful waiting is certainly the best first step, because about half of them will get better just on their own spontaneously within a few weeks.  In our system, once a person gets to the doctor's office, there is a quick trigger response to make the diagnosis and put them on medication that will [?unclear 22:26] it.  And then when the person gets better, we have what we call placebo response, and about half the people with mild problems have a placebo response.  They don't know what caused them to get better, so they'll often misattribute the gains to the medication taken not realizing the fact that they would have gotten better on their own.  So, I think, as a country, we would be a lot better off trusting to natural resiliency- not jumping to the diagnosis when the problem is mild.  And there is another flip side to this that is particularly tragic; while we are over-diagnosing and over-treating people with mild problems that probably very often don't need it we're ignoring people who have severe problems.  Only 1/3 of people with severe depression see a mental health clinician.  The budgets for treating severe psychiatric disorders have been slashed drastically in the last few years because of the economic difficulties in the states.  So, we're terrifically undertreating people that have clear-cut severe psychiatric disorders who could benefit for sure from our efforts.  And, as a country, we are over-treating people who are probably- in many instances- might be much better off without psychiatric diagnosis and without psychiatric treatment. 

Rob:   So, what strikes me about what you just told me is this requirement for a diagnosis-for treatment.  That means that psychiatry is being driven by insurance company policies. 

Allen:  And even worse, primary care, because at least when the psychiatrist has made the diagnosis, he's probably spent some time with the patient and he has some expertise in making the diagnosis.  The primary care doctor is basing the toughest diagnostic quandaries-because the people they see are on the boundary between normality and psychiatric disorder- and they are jumping to a diagnosis in a few minutes without the benefit of the time required, the watchful waiting period that is often useful, and the training.  So, many people get labeled with a diagnosis they don't need, and some of the diagnoses stick on you in a haunting kind of way.  It's a lot easier to make a diagnosis than to get rid of one if it's wrong.  So, sometimes once it gets on the record, it takes on a life of its own; and, I've talked to any number of people who have been stigmatized terribly by getting a diagnosis-usually bipolar disorder- that didn't apply to them, was made casually.  The doctor would say something like, "You have a little bipolar disorder."  But, once it gets in the record, it lives on, and you may have trouble adopting a child, you may have trouble getting life insurance, because the diagnosis will haunt you even if it is incorrect. 

Rob:  So, the worst diagnoses in terms of stigmatizing people are bipolar disorders?  Any other ones?

Allen:  Well, I think Schizophrenia would carry the stigma, but it's not mislabeled nearly as often as bipolar disorder.  It has been a kind of fad in diagnosing adults-actually kids- incorrectly with bipolar disorder during these last 15 or so years.  It is part of the success of anti-psychotics that they have gotten an indication for bipolar, and the advertising was able to convince many patients and also many doctors that bipolar disorder was being terribly underdiagnosed and that lots of people had it.  And so, there is a tendency to take the slightest degree of mood liability and misdiagnose it as bipolar disorder.  And lots of people have the diagnosis of bipolar disorder that probably have been mislabeled.  Let me make a point here though, that I don't want people to listen to this and just stop their medication.  The two bad things that can happen when you have a psychiatric disorder-one is being mislabeled and getting medication you don't need, but equally bad would be assuming you have been mislabeled when you really need the medicine-when the diagnosis is accurate- and stopping it on your own.  And the worst result of this phone call would be someone who really needs the medicine with a diagnosis that really does make sense stopping the medicine thinking that I am being so critical of psychiatry and psychiatric medicine that their best bet would be to stop it.  For people who need psychiatric medicine, for people who have a true psychiatric diagnosis, the medicine is enormously helpful.  So, there are some anti-psychiatry folks who try to criticize the field at large --they're dead wrong.  Psychiatry does a tremendous amount of good, and these medicines are sometimes essential- indeed lifesaving- for people.  So, no one should say it is a trivial decision to go off medication, because if you need it, you really do need it.  On the other hand, it is not a trivial decision to go on medication.  If you don't need it, it's not necessary to take it; it may be bad for you.  So, the trick is figuring out which category you are in, to sort of take a hard look at your symptoms, to discuss them in detail with your family and with physicians, to become a very informed and smart consumer, so that you are not going to fall into either trap of over diagnosis and over medication or under diagnosis and under medication.  Our country has both of these problems.  You have way too many people getting medicines they don't need, and way too many people not getting medicines they desperately need.  And so I think the only way to try to work in this labyrinth if you are a consumer is to get lots of knowledge yourself, to share with your family so you get a second opinion from them, to ask questions of the doctor and get reasonable answers- if their answers don't seem reasonable, to get second and sometimes even third opinions.  I think that the decision to be on or not be on a psychiatric medication is a major one in a person's life.  It requires all the thought that you would put into a decision on who you are going to marry, what car you are going to buy, what house you are going to buy.  It should be done very carefully; it shouldn't be done casually in a primary care doctor's office after seven minutes.  And, it shouldn't be done casually by the person themselves listening to this phone call deciding that they are going to go off their medicine.  It is a very serious decision one way or the other. 

Rob: Wow! So, that's pretty intense advice- going on a psychiatric medication should be considered as seriously as you consider the person you are going to marry.  So, what you've basically said here is there are a lot of people who are inappropriately prescribed medications, but there are a lot of people who need the medications and it will help them and maybe change their lives and maybe even save their lives.  And, I've seen that.  I totally agree with you.  How do people decide?  I mean, here you've got somebody obviously going through something in their life that is bringing them to their GP, and the GP says, "Well, it looks to me like you're bipolar.  I've got some samples from the pharmaceutical company.  Why don't you try these and see how you do; and then, here is a prescription that you can get filled."  Now your response is that people need to be good consumers.  They are under all kinds of stress or something is going on in their lives that brought them to the doctor.  They are feeling really like they want help.  It's not an easy time to just very calmly say, "Ok.  Let me be a good consumer."  What would you suggest that they do when they are encountering this situation?  It sounds like the one where they are at the greatest risk for being inappropriately put on medication.

Allen:  You're right on the money, and I think that bad decisions are made in situations where people are under stress and feel need for urgent relief.  And, those bad decisions sometimes hurt for a lifetime, because many times people will stay on medication for years, and maybe for life, that they wouldn't have needed in the first place if they had just waited a couple of weeks and they would have gotten better on their own.  I really can't emphasize enough that it is not a trivial decision; it has been made a trivial decision with the sort of propaganda that psychiatric disorder is everywhere and that the medications are the only way to correct chemical imbalance- that's kind of a myth, because all problems in life are a chemical imbalance- and that the medicines are completely innocuous and you just pop a pill and you'll feel better.  I think that's dead wrong.  I think that this is a very, very serious decision that often has consequences that will go on for years, and that unless- I think if you have a clear-cut psychiatric disorder and it pops off the page that you are a classic case, and if it is urgent, then by all means treatment should be started right away: diagnosis should be made, effectively, quickly, immediately, and everything should be done to solve the problem as soon as it's been clearly identified.  But for those mild problems that are in between normal and mental disorder- and this is the majority of people who are taking medicine who would be in that category; there are only 5% of the population who has a severe mental disorder.  Three times as many people are being diagnosed with mild problems.  For those problems, people should be aware of the fact that they often go away on their own, that in studies, 50% of people in that category will have a placebo response.  It gets better without the active medication.  And that unless there is something urgent, unless the problem is really clear cut, the best bet is watchful waiting at the beginning to see how time and natural healing affect things.  The second intervention after watchful waiting should be counseling and education, not pills.  And, I would say that for this group, pills should be a third that is reserved when time and counseling haven't worked.  Counseling works as well as pills for mild to moderate problems in psychiatry.  So, I think that the tendency because there is a huge drug industry and the drug industry in total spends something like 30 billion dollars a year on advertising- and just in the anti-psychotic drugs alone they are spending I think something like three billion dollars a year on advertising- there is no constituency, there is no propaganda campaign for watchful waiting.  There is no advertising for psychotherapy.  And, so this is an imbalance in the way consumers have come to understand psychiatric problems with a very strong commercial interest trumpeting the benefits of medication even in certain situations where it doesn't make sense.  And that has led to the imbalance.  I think that if you are a consumer, you shouldn't trust the commercials.  I mean, one thing for sure- don't ask your doctor after seeing a commercial, because once you ask your doctor it is likely to trigger the reaction.  You have the diagnosis, you get the pill.  I would always be doing research first on my own.  I understand that people with psychiatric problems are under stress.  I understand that many of them may not have great insight as part of the problem or part of the stress.  But, what I am trying to emphasize is the importance of individuals and of families taking part in the decision making.  You can only do this if you learn as much as possible.  And, you have to be cautious of what you learn, because lots of the stuff on the internet itself has been influenced by drug companies, so that there is no one safe place to go where you'll be absolutely sure that the information you get is reasonable.  But, I would always trust sights that are non-profit more than I would trust sights that have anything to do with profit.  If you are seeing advertisements on the side of the page, it is likely that the content may have been influenced by the companies involved.

Rob:   >From what I understand, the treatment of these acute problems, bipolar disorder and schizophrenia, can be very different in other countries so that drug intervention as the primary treatment is not always the case.  Often it is creating a therapeutic milieu or community and that, from what I understand, in those situations the recovery rate is much, much higher.    

Allen:  Well, I would put it a different way.  If someone has clear-cut bipolar disorder, if someone has severe depression, if someone has schizophrenia, severe OCD, very severe panic disorder- in these situations medication is almost always necessary along with psychotherapy, along with social retraining and other skill training.  I think that the more severe the problem and the more clear-cut the problem, the more medication will be part of the treatment plan.  The problem we have here is pills being used for problems that are very mild that would get better. 

Rob:   I think I lost him.  Yes, we've lost him.  So, he'll be back in a minute with a different phone.  What I got that information from is, I guess, two years ago, I attended a conference for psychologists for social responsibility, and there was a panel reporting that in countries where there is a better social safety net- now I'm not talking about Medicare or Social Security or anything like that; I'm talking about families and communities that are there to help people who are having problems- in that kind of milieu, from what I understand, people get better at a much higher rate: double the rate.  And, actually, the numbers for people who are only put on medication are not nearly as good.  So, that's one piece of it.  Another piece is- and I'm going to be asking Dr. Frances about this- is this idea of people prescribing medications for bipolar disorder to children, and prescribing ---- oh, you're back!      

Allen:   I'm back. 

Rob:  Alright, so what I was saying while you were gone is that one of the problems that I understand exists, in terms of this over-diagnosing and over-prescribing, is with the kids with bipolar disorder.  Is there even a diagnosis for childhood bipolar disorder in DSM 4?

Allen:  No.  The criteria in DSM 4 is the same for adults.  It is that the kids would have to have cyclical episodes of clear-cut mania and depression.  The suggestion was made for DSM 4, going back twenty years, that there be a separate criteria for kids that would recognize that they are developmentally different and that children are in different cycles and that instead there are children who are irritable, who have temper tantrums, who are conduct problems, and that these may be precursors to bipolar disorder.  We shot down this idea, because we didn't think that there was enough evidence for it and we realized that it might lead to wild over-diagnosis.  This didn't discourage the drug companies, and in collaboration with a few thought leaders in the field of child psychology who promoted this idea very strongly, they were able to convince the field.  They were able to convince not just child psychiatrists, but pediatricians and family care doctors.  The rates of childhood bipolar disorder have jumped forty times in the last fifteen years, and the direct consumer advertising was a wonderful way of promoting this, because you could get the parents on board, teachers on board, with the idea that any kid who had a conduct problem was really bipolar, and that giving medication for that problem would be helpful.  The result has been an enormous overuse of drugs in kids, and the drugs are particularly harmful in kids, because they cause tremendous weight gain.  The average 11-12 year old who weighs 110 pounds will gain 12 pounds in 12 weeks on an anti-psychotic drug.  They'll jump up from 110 pounds to 122 pounds in just three months.  We already have an epidemic of childhood obesity.  Obesity is a risk factor for diabetes and cardiovascular disease and for shortened life expectancy.  And so, does it make sense for us to be using what is essentially a fake diagnosis, because childhood bipolar disorder has not been something that is well studied or concerned- to give kids medication that may cause them so much lifetime harm?  It just doesn't, in my view, it is one of the worst fads- I think that there are a number of different fads in psychiatric diagnosis- this is, I think, probably the least justified and the most dangerous of the current fads in psychiatric diagnosis. 

Rob: Fads in psychiatric diagnosis; ok, I want to cover that, but first I want to pick up on one thing you said.  Being put on a psychiatric medication, like what would be used for bipolar disorder, reduces your life expectancy doesn't it? 

Allen:   Ok, I don't want you to exaggerate this too much.  I think that if you need the medicine, the medical risks of obesity, diabetes and cardiovascular disease are definitely worth it, because the risks of not being treated are greater.  These medicines are enormously useful, essential, for people who need them, and someone taking an anti-psychotic for a good reason should certainly stay on them.  But, taking these medicines casually, because there were samples on the shelf of your primary care doctor and he said after seven minutes you might benefit from them; I think that is what I am trying to fight against.  I'm almost as worried about the people who- I'm in some ways equally worried- about the people who aren't getting medication they need as I am about the ones who are getting too much medicine.  So, we have a misallocation where lots of people absolutely definitely have a diagnosis or require medication that are not getting it, because we have insufficient funding, because sometimes they are hard to get into treatment, and at the same time people who don't need it are being given it casually and taking on the risks without there being much benefit.  

Rob:   Ok, so there were two pieces: one, I know that if you need the medication and you go off it, it may not work if you go back on it.  Isn't that true?

Allen:  Everyone is different; there is a variable, but it certainly is not a good idea if you've had a good response to medicine to go off it without great care and thought about the risks and benefits. 

Rob: If it is provisioned by a psychiatrist.

Allen:  I would say yeah, definitely.  I should state that the longer a persons' brain has a psychiatric symptom, the more embedded it tends to be, so that if a person has mania and has lots of manic episodes, it may make it more likely to have manic episodes in the future and it may make it, as you suggest, more likely that they will have difficulty being treated for the next manic episode.  So it is a very good idea to get there early and to treat thoroughly real psychiatric symptoms.  But on the other hand, it is equally important that we not get there so early that we are treating fake psychiatric symptoms and giving medication that is not indicated.  And, what we've done is provide way too little money in treating the serious and obvious psychiatric symptoms and way too much money being wasted on treating situations that would do better on their own. 

Rob:   So, again it goes back to what you said- going on psychiatric medications like you would, selecting the person you are going to marry-take it very seriously, don't just jump on it.  And so, I have a question.  What percentage of people who are put on these anti-psychotic medications don't really need them?  Is there any research on that? 

Allen:   It is hard to say.  I think we know a little bit more about depression.  11% of the population is taking an anti-depressant.  In the surveys, only 3% of the 11%- a little less than one fourth- have actual depression symptoms at the moment they are taking the medication.  So, 3% have depression symptoms, 8% don't but they are still taking the medications.  Now, some of those 8% should be on medicine, because it serves a preventive purpose.  If someone has had loss or depression symptoms in the past and they responded to medication, you don't want to stop the medication.  If someone has chronic depression and they respond to medication, even though they don't have symptoms at that moment, the medication is serving a useful purpose.  But, lots of people go on the medication during a time when they were going to get better anyway, that have a 50% placebo response rate.  And, of the 8%, no one knows for sure, but it is a safe bet that at least half would be people who don't really need to be on the medication.  So, my guess is- and it is a very rough guess, there is no right answer to this- if we have 11% of the population taking anti-depressants, maybe two thirds of those people really need them and maybe one third don't.  I think that with anti-psychotics, the ratio is probably even worse, because they have been so heavily publicized for off-label use.  Twenty percent of people with anxiety disorders now are getting an anti-psychotic on top.  They are being given out like sugar water, and they are really not sugar water.  So, again, if someone has a clear-cut bipolar disorder or schizophrenia, they should stay on their medicine.  I don't want anyone to be discouraged from hearing this.  On the other hand, if you are getting an anti-psychotic for another indication, maybe you need it, but I would do a lot of research on it and I would discuss it with a doctor; and it has to be a good reason.  If a doctor can't explain something in ways you understand, it is a good time to get a second opinion. 

Rob: If somebody is put on a medication and they don't really need it; what are the adverse side-effects, the iatrogenic effects of it?

Allen:  It varies medication by mediation, it varies by dose, it varies with time, and some of these are just unknown.  We don't know what the effect would be of putting people at the age of six on medication; what affect that will have fifty or sixty years later, because there just hasn't been time to study it.  So I think it's very specific to the individual medicine.  Amongst the drugs available on the market now, by far the most problematic are the long term effects of anti-psychotics.  This weight gain issue is enormous even though the medicines themselves are initially well tolerated in the short run.  For people who gain weight on them, that is a huge issue that has to factored in.  I think that there is way too much anti-anxiety medicine being spread out.  Xanax is a very popular drug in primary care for anxiety.  The dose that is effective is very close to an addictive dose, so that once on a heavy dose of Xanax it is very hard to get off of it.  The withdrawal symptoms mimic anxiety or are worse than the anxiety you had when you started, so that if you try to stop the pill you think you are having a relapse and you have to stay on it.  So there are real addictive problems with the anti-anxiety agents, particularly Xanax, and they are way over-used in primary care.  And then there is the real elephant in the room, and those are narcotic prescription medications that have taken off and in many instances are replacing street narcotics.  They are often responsible- in conjunction with many anti-anxiety elements or alcohol- with drug overdoses and with prescription addiction.  It is a huge problem in the military: 110,000 of our soldiers are on psychotropic drugs, 110,000- I think about 8% of the active duty.  And many of them are receiving more than one drug.  There are instances where soldiers actually die because of the prescription medicines that they have received; they have overdoses of prescription medication, and they are often also used in suicide attempts.  So, I think that if I had to pick the most dangerous drugs that are being prescribed, I'd probably put the narcotic pain medicines up there first, the anti-anxiety agents for their addiction problems, and the anti-psychotic medications because of the weight gain. 

Rob:  And what about these kids being put on stimulant medications: Adderall and Ritalin and what have you under the diagnosis of Attention Deficit Hyperactivity Disorder?

Allen:  Thank you; I think that there are some kids for whom these medicines are absolutely helpful and even essential in their getting a decent education and being able to function in school and with family.  The problem is that the rates of ADHD have tripled and the rates of medication use have sky-rocketed, so that they are currently being used for kids who are probably essentially showing individual difference or developmental lags but don't really have a mental disorder.  A really chilling study comes from Canada: they found- this is a large sample, about ten thousand kids- that one of the best predictors of getting a diagnosis of ADHD and getting medication was when you were born.  If you were born in December, you had a tremendously lower rate- about 70% in boys- of ADHD than if you were born in January.  And, the reasons are simple; that that was the cut-off for school.  The youngest kid in school is most likely to be developmentally immature and most likely to get the diagnosis of ADHD, most likely to be put on medication.  We have this strange, weird situation where we are medicalizing immaturity; we're medicalizing the youngest kid in the class.  Each of the diagnoses and each of the treatments make a lot of sense if it is done appropriately where the symptoms are severe and enduring.  The trouble is, when you have fads, and it's like any kind of fashion- there is a huge overshoot.  And so kids that don't really need the diagnosis, who would be better left alone or better monitoring, or watchful waiting, or parent training, or maybe school systems could pay more attention to individual kids; a lot of this- of what gets diagnosed as ADHD- may have to do with a school system that is under trained and the easiest way of dealing with it is to medicate each kid. 

Rob:   Now, when you medicate a kid with ADHD that has its own risks as well.  What are the risks when you put a child on stimulant medication?  Isn't it true that sometimes that can actually precipitate other more severe problems as well?

Allen:   Well, as far as a tendency toward bipolar disorder, there is a risk that it is going to stimulate that.  There is sleeplessness, there is lack of/difficult with appetite, not gaining weight, not growing as you might expect, there are very rare instances where you get behavioral problems exacerbated, but they are real, and very, very occasional cardiovascular problems.  And also, there is a huge secondary market; 30% of college kids and 10% of high school kids will have used someone else's stimulant medication.  There is a secondary market with kids either selling or giving away their medicines to their friends, and the medicine is being used more and more for performance enhancement or recreation by people who have either faked a diagnosis or have gotten the diagnosis too casually and are in some instances handing it around to the market or to their buddies.  I think that if someone has a substance abuse risk, one of the great ways of getting supplies is to go to your doctor and say that you have these symptoms.  They are very easy to describe, and if your doctor is a very loose prescriber-and they are- there is a very quick prescription of a stimulant medication that may actually be addicting for that person or exacerbate psychiatric problems.  I don't think we should have the assumption that every person who has distractibility or hyperactivity needs medication.  And one of the problems in DSM 5 is that it will make it much easier for adults to get a diagnosis of ADHD and adult distractibility can be caused by any number of psychiatric problems as well as just a part of life.  If we make it easy for adults to get ADHD, I think that will be the next fad.  The next diagnosis d'jour would be that lots of people are going to think they have ADD and they'll be getting medication they don't need often for recreational purposes or for performance enhancement.  I don't think that we should be handling medical diagnosis this way; I think it should be carefully done and the medication step should be equally thoughtful.  There should be a clear reason every time someone takes a medication.

Rob: "Station ID" I'm speaking with Dr. Allen Frances.

Allen:   I think I'm going to have to go soon. 

Rob:   Ok.  Just wrapping it up; Dr. Frances was the chair of DSM 4 task force and the department of psychiatry at Duke University.  I wanted to take a kind of bigger picture look at this.  With DSM 5, it is going to change America; it is going to change the percentage of people who are diagnosed, the percentage of children who are diagnosed and labeled.  It is going to change the numbers by the millions of people who are put on psychiatric medications.  Isn't that so?

Allen: Well, it's hard to know what the impact will be.  Not everyone who will qualify for a diagnosis will get one, so that these [? 53: 42] studies, which show that tens of millions of people might be diagnosed who would have been diagnosed before if they went to the doctor and asked for the diagnosis- but not all of them will do that.  I think it could have a substantial negative effect, and that's why I'm so concerned about it. 

Rob:   What I'm concerned about is this is no small change.  Because of how influential the DSM has become, it could change our American culture, and I'm curious if you have had any thoughts on that really big picture?  DSM 4 really took off, and DSM 5 is going to drastically expand the percentage of people who are diagnosed or medicated.  How do you see that changing the American culture as compared to other places where they don't do it this way?

Allen:  I think that a lot of the damage has already been done.  I think we have a situation where we are using way too many medications for way too many fake diagnoses.  I think that DSM 5 will make that worse; DSM 5 will turn the temper tantrums of children into something called a Disruptive Mood Disregulation Disorder.  It'll turn the normal forgetting of old age into something called Minor Neurocognitive Disorder.  It'll turn gluttony into Binge Eating Disorder.  It'll make grief into major depression.  So these are some serious problems, but I wouldn't underestimate the problems we already have before DSM 5.  It may help to turn what is already a severe diagnostic inflation into something of a diagnostic hyper-inflation, but we already have the problem.  It's not just DSM 5's fault; it's something that we are living with now, and I think the major hope that this can be reversed is the tobacco industry.  Thirty years ago the tobacco industry was all-powerful, and who would have thought that at this point smoking would have been reduced from 60% to 20% or less in the population.  It went from a sexy habit to a dirty secret in the lives of the people who continue doing it.  The odds were against this ever happening because of the huge financial power of the tobacco industry, but it did happen.  And, I think the pharmaceutical industry has tremendously overstepped, and that even though it has enormous resources and tremendous political pull, that people may come to their senses and realize that we have to pull back and try to use the medications more thoughtfully where they belong.  The companies are constantly being fined.  There have been- over the last ten years- more than a dozen very large fines: the biggest is three billion dollars, another 1.5 billion dollars for off-label illegal marketing, in some cases criminally illegal, of their products- anti-psychotics and anti-depressants particularly.  So, there has been a government push-back against illegal drug company practice, but the fines- even the three billion dollar fine- is just the cost of doing business when the profits are so large.  I think that if some of the company directors wound up being hit more with personal fines or going to jail, if patents were shortened or illuminated for drugs where there had been illegal marketing, if the penalties were greater I think the companies would be under better control.  I think the idea that companies are allowed to market to consumers is outrageous, not done anywhere else in the world; that should be stopped.  It's better now than it was years ago, so there have been efforts to monitor the pharmaceutical industry, and think that they are successful to some degree but a lot more needs to be done.  I have to go.

Rob:  Ok. Thank you so much!  You have been a great interview, and keep up writing about this.  We need people warning us what is going on here.

Allen:  Thank you; and you ask good questions.  You're a smart guy.  Thanks very much.

Let's Call the Whole Thing Off

Psychiatric Times
By Irwin Feinberg, MD
May27, 2010
Dr Feinberg is Professor of Psychiatry at the University of California at Davis

A vital consideration we learn in medicine is that continuing life support for a moribund patient past a certain point is harmful to the lives of all concerned. We have reached that point with DSM5. Dr Allen Frances has outlined compelling clinical arguments against many of the new disorders DSM5 proposes and he has shown how their adoption could have far-reaching, unintended, and damaging consequences for the patients we have pledged not to harm, and for society generally.

I write from the vantage point of 50 years of psychobiological research. Most of it is in the field of sleep neuroscience. However, as often happens in science, one thing leads to another and my observations enabled me to propose that the human brain undergoes a profound reorganization during adolescence driven by synaptic pruning and that some cases of schizophrenia might be caused by errors in this process.1 My association at NIMH with Edward V. Evarts, one of the great neurophysiologists of the last half century, stimulated me to propose that the hallucinations of schizophrenia result from a failure of feed-forward mechanisms that distinguish self-initiated neural activity from that produced by external stimulation, resulting in auditory hallucinations and other first-rank symptoms.

It is difficult and time-consuming to produce reliable new knowledge; it cannot be accomplished by committee fiat, as Drs Kupfer, Schatzberg and Regier seem to be believe. Dr Frances has mentioned the damage to psychiatric research that several new, ill-conceived categories in DSM5 could inflict. He also pointed out that changing nomenclature and diagnostic standards in the absence of compelling scientific justification will severely damage psychiatric research as well as clinical practice. Many of these changes would make it impossible to compare decades of epidemiological results with new findings. Moreover, the sloppy thinking and language in the proposed revision will be apparent to any educated layman. The “field trials” and timetables proposed for new categories are laughable to any statistically trained psychologist. The inevitable public exposure of the gross defects in DSM5 will bring our entire field into disrepute and diminish public support for the research we need.

There have been no research advances that demand new diagnoses and syndromes. Despite many intriguing findings, no psychiatric disease can be diagnosed by a biological or psychological test. If the DSM5 committee believes that new genetic or imaging findings justify a revised nomenclature, they should indicate which ones. Instead of creating dangerous new categories, let us discontinue DSM5 development and use its funding to make strong bridges between DSM-IV and ICD 11. We should also work to diminish or eliminate the huge differences between the US and the UK in the incidence of diagnoses like ADHD and pediatric bipolar disorders. These differences make it impossible to compare cross-national biological research on the same diagnostic categories, even in countries with similar cultures and medical traditions.

The proposed DSM5 would be a giant step backwards for psychiatry. American psychiatrists should petition the APA to drop this ill-conceived and badly executed project.

When mental disorders aren't

Boston Herald
Psychiatrist Allen Francis
Monday, March 22, 2010

As chairman of the task force that created the current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), which came out in 1994, I learned from painful experience how small changes in the definition of mental disorders can create huge, unintended consequences.

Our panel tried hard to be careful, but inadvertently contributed to three false “epidemics” - attention deficit disorder, autism and childhood bipolar disorder. Our net was cast too wide and captured many “patients” who might have been far better off never entering the mental health system.

The first draft of the next edition of the DSM, posted for comment last month, is filled with suggestions that would multiply our mistakes and extend the reach of psychiatry dramatically deeper into the ever-shrinking domain of the normal. This could create tens of millions of innocent bystanders who would be mislabeled as having a mental disorder. The pharmaceutical industry would have a field day.

The manual, prepared by the American Psychiatric Association, is psychiatry’s only official way of deciding who has a “mental disorder” and who is “normal.” The quotes are necessary because this distinction is very hard to make at the fuzzy boundary between the two.

Where the DSM-vs.-normality boundary is drawn also influences insurance coverage, eligibility for disability and services, and legal status - to say nothing of stigma.

What are some of the most egregious invasions of normality suggested for DSM-V? “Binge eating disorder” is defined as one eating binge per week for three months. (I, along with more than 6 percent of the population, would qualify.) “Minor neurocognitive disorder” would capture many people with no more than the expected memory problems of aging. Grieving after the loss of a loved one could be misread as “major depression.” “Mixed anxiety depression” is defined by commonplace symptoms difficult to distinguish from the emotional pains of everyday life.

The recklessly expansive suggestions go on. “Attention deficit disorder” would become much more prevalent in adults, encouraging the already rampant use of stimulants. A category for temper could capture kids with normal tantrums.

The sexual disorders section is particularly adventurous. “Hypersexuality disorder” would bring great comfort to philanderers. “Paraphilic coercive disorder” introduces the dangerous idea that rapists merit a diagnosis of mental disorder if they get sexual excitement from raping.

Experts have an almost universal tendency to expand their own favorite disorders. This therapeutic zeal creates a huge blind spot to the great risks that come with unnecessary treatment.
Allen Frances is former chairman of psychiatry at Duke University.

Pfizer Broke the Law by Promoting Drugs for Unapproved Uses

Bloomberg News
November 9, 2009
By David Evans

Nov. 9 (Bloomberg) -- Prosecutor Michael Loucks remembers clearly when lawyers for Pfizer Inc., the world’s largest drug company, looked across the table and promised it wouldn’t break the law again.

It was January 2004, and the attorneys were negotiating in a conference room on the ninth floor of the federal courthouse in Boston, where Loucks was head of the health-care fraud unit of the U.S. Attorney’s Office. One of Pfizer’s units had been pushing doctors to prescribe an epilepsy drug called Neurontin for uses the Food and Drug Administration had never approved.

In the agreement the lawyers eventually hammered out, the Pfizer unit, Warner-Lambert, pleaded guilty to two felony counts of marketing a drug for unapproved uses.

New York-based Pfizer agreed to pay $430 million in criminal fines and civil penalties, and the company’s lawyers assured Loucks and three other prosecutors that Pfizer and its units would stop promoting drugs for unauthorized purposes.

What Loucks, who’s now acting U.S. attorney in Boston, didn’t know until years later was that Pfizer managers were breaking that pledge not to practice so-called off-label marketing even before the ink was dry on their plea.

On the morning of Sept. 2, 2009, another Pfizer unit, Pharmacia & Upjohn, agreed to plead guilty to the same crime. This time, Pfizer executives had been instructing more than 100 salespeople to promote Bextra, a drug approved only for the relief of arthritis and menstrual discomfort, for treatment of acute pains of all kinds.

Record High Fine

For this new felony, Pfizer paid the largest criminal fine in U.S. history: $1.19 billion. On the same day, it paid $1 billion to settle civil cases involving the off-label promotion of Bextra and three other drugs with the U.S. and 49 states.

“At the very same time Pfizer was in our office negotiating and resolving the allegations of criminal conduct in 2004, Pfizer was itself in its other operations violating those very same laws,” Loucks, 54, says. “They’ve repeatedly marketed drugs for things they knew they couldn’t demonstrate efficacy for. That’s clearly criminal.”

The penalties Pfizer paid this year for promoting Bextra off-label were the latest chapter in the drug’s benighted history. The FDA found Bextra to be so dangerous that Pfizer took it off the market for all uses in 2005.

Across the U.S., pharmaceutical companies have been pleading guilty to criminal charges or paying penalties in civil cases when the U.S. Department of Justice finds that they deceptively marketed drugs for unapproved uses, putting millions of people at risk of chest infections, heart attacks, suicidal impulses or death.

$7 Billion in Penalties

Since May 2004, Pfizer, Eli Lilly & Co., Bristol-Myers Squibb Co. and four other drug companies have paid a total of $7 billion in fines and penalties. Six of the companies admitted in court that they marketed medicines for unapproved uses.

In September 2007, New York-based Bristol-Myers paid $515 million -- without admitting or denying wrongdoing -- to federal and state governments in a civil lawsuit brought by the Justice Department. The six other companies pleaded guilty in criminal cases.

In January 2009, Indianapolis-based Lilly, the largest U.S. psychiatric drug maker, pleaded guilty and paid $1.42 billion in fines and penalties to settle charges that it had for at least four years illegally marketed Zyprexa, a drug approved for the treatment of schizophrenia, as a remedy for dementia in elderly patients.

In five company-sponsored clinical trials, 31 people out of 1,184 participants died after taking the drug for dementia -- twice the death rate for those taking a placebo. Those findings were reported in an October 2005 article in the Journal of the American Medical Association.

‘Don’t Respect the Law’

“Marketing departments of many drug companies don’t respect any boundaries of professionalism or the law,” says Jerry Avorn, a professor at Harvard Medical School in Boston and author of “Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs” (Random House, 2004). “The Pfizer and Lilly cases involved the illegal promotion of drugs that have been shown to cause substantial harm and death to patients.”

The widespread off-label promotion of drugs is yet another manifestation of a health-care system that has become dysfunctional.

“It’s an unbearable cost to a system that’s going broke,” says Avorn, who heads the pharmacology economics unit of Brigham and Women’s Hospital in Boston. “We can’t even afford to pay for effective, safe therapies.”

10 Million Prescriptions

About 15 percent of all drug sales in the U.S. are for unapproved uses without adequate evidence the medicines work, according to a study by Randall Stafford, a medical professor at Stanford University in Palo Alto, California.

He estimates that doctors write more than 10 million such prescriptions each year.

As large as the penalties are for drug companies caught breaking the off-label law, the fines are tiny compared with the firms’ annual revenues.

The $2.3 billion in fines and penalties Pfizer paid for marketing Bextra and three other drugs cited in the Sept. 2 plea agreement for off-label uses amount to just 14 percent of its $16.8 billion in revenue from selling those medicines from 2001 to 2008.

The total of $2.75 billion Pfizer has paid in off-label penalties since 2004 is a little more than 1 percent of the company’s revenue of $245 billion from 2004 to 2008.

$36 Billion in Revenue

Lilly already had a criminal conviction for misbranding a drug when it broke the law again in promoting schizophrenia drug Zyprexa for off-label uses starting in 1999. The medication provided Lilly with $36 billion in revenue from 2000 to 2008.

That’s more than 25 times as much as the total penalties Lilly paid in January.

Companies regard the risk of multimillion-dollar penalties as just another cost of doing business, says Lon Schneider, a professor at the University of Southern California’s Keck School of Medicine in Los Angeles.

In 2006, he led a study for the National Institute of Mental Health of off-label use of drugs, including Zyprexa, for the treatment of Alzheimer’s disease.

“There’s an unwritten business plan,” he says. “They’re drivers that knowingly speed. If stopped, they pay the fine, and then they do it again.”

Shareholders Unmoved

Schneider has been paid both by Lilly as a consultant and by plaintiffs suing the company.

Big Pharma’s off-label transgressions didn’t trigger a rush for the doors by shareholders. From Jan. 26, when Pfizer announced that it would pay billions in penalties, to Oct. 12, Pfizer’s share price increased 9.3 percent, just shy of the 11.2 percent rise in the Standard & Poor’s 500 Health Care Index.

From Oct. 21, 2008, when Lilly said it would pay its penalties, to Oct. 12, the company’s stock value went up 0.6 percent; the S&P index gained 6.9 percent in that time.

In pushing off-label use of drugs, companies find ready and willing partners in physicians. Under the fragmented system of medical regulation in the U.S., it’s legal for doctors to prescribe FDA-approved drugs for any use.

The FDA has no authority over doctors, only over drug companies, regarding off-label practices. It’s up to the 50 states to oversee physicians.

“I think the physician community has to take some ownership responsibility and do their own due diligence beyond the sales and marketing person,” says Boston’s former U.S. Attorney Michael Sullivan.

Off-Label Benefits

Loucks says prosecutors realize that patients can benefit when doctors use drugs for off-label purposes based on science and not on false marketing claims.

Doctors generally don’t tell people that they’re prescribing drugs pitched to them by pharmaceutical salespeople for unapproved treatments, says Peter Lurie, deputy medical director of Public Citizen, a Washington-based public interest group.

Most physicians don’t keep track of FDA-approved uses of drugs, says Lurie, a physician who has published articles in “The Lancet” and the “Journal of the American Medical Association.”

“The great majority of doctors have no idea; they don’t even understand the distinction between on- and off-labeling,” Lurie says.

Pharmaceutical companies have showered doctors with cash to persuade them to use drugs off-label, according to their guilty pleas.

‘Buying Access’

Pfizer’s marketing program offered doctors up to $1,000 a day to allow a Pfizer salesperson to spend time with the physician and his patients, according to a whistle-blower lawsuit filed by John Kopchinski, who worked as a salesman at Pfizer from 1992 to 2003.

“By ‘pairing up’ with a physician, the sales representative was able to promote over a period of many hours, without the usual problems of gaining access to prescribing physicians,” Kopchinski says. “In essence, this amounted to Pfizer buying access to physicians.”

Pfizer spokesman Chris Loder says the company stopped what it calls “mentorships” in 2005. He says Pfizer paid doctors $250 per visit.

It used to be legal for companies to promote drugs for any use in the U.S. Congress banned the practice in 1962. The catalyst was Thalidomide, a morning sickness drug taken by pregnant women outside the U.S. that caused severe birth defects.

Recouping Investments

The 1962 law required pharmaceutical companies to prove their drugs were safe and effective for specific uses. Before that, a drug company could market an approved medicine for any illness.

If the law is clear, why do drug companies keep breaking it? The answer lies in economics. Pharmaceutical companies spend about $1 billion to develop and test a new drug. To recoup their investment, the companies want doctors to prescribe their drugs as widely as possible.

Pfizer’s Neurontin is a case in point. The FDA approved the drug as a supplemental medication in treating epilepsy in 1993. Pfizer took in $2.27 billion from sales of Neurontin in 2002. A full 94 percent -- $2.12 billion -- of that revenue came from off-label use, according to the prosecutors’ 2004 Pfizer sentencing memo.

Pfizer, which bought Wyeth on Oct. 15 for $68 billion, put itself at the center of illegal off-label drug marketing with an acquisition frenzy a decade earlier. From 1995 to 2005, Pfizer purchased more than 20 companies.

Guilty Pleas

Since 2004, companies that are now Pfizer divisions have pleaded guilty to off-label marketing of two drugs. Pfizer continued off-label promotions for these medications after buying the firms, according to Pfizer’s Sept. 2 guilty plea and FDA correspondence with Pfizer.

Pfizer first stepped into an off-label scheme in 1999, when it offered to buy Morris Plains, New Jersey-based Warner-Lambert Co. Prosecutors charged that Warner-Lambert marketed Neurontin off-label between 1995 and 1999.

Warner-Lambert admitted doing so for one year in a May 2004 guilty plea for which Pfizer paid $430 million in fines and penalties.

Neurontin, which was invented by Warner-Lambert, was first tested in humans in 1987. When the FDA approved it in 1993 to be used only along with other epilepsy drugs, the agency wrote that a side effect of the drug can be that it induces depression and suicidal thoughts in patients.

Whistle-Blower

Much of what prosecutors learned about Warner-Lambert’s marketing of Neurontin comes from a former employee.

David Franklin, who holds a Ph.D. in microbiology from the University of Rhode Island, left his job as a pediatric researcher at Harvard University’s Dana-Farber Cancer Institute in 1996 to work for the Parke-Davis unit of Warner-Lambert in Boston.

He says he hoped the salary boost -- to $55,000 annually from $18,000 -- would help him pay off student loans and better support his family.

Franklin’s title at Warner-Lambert was medical liaison. He says he soon realized his new employer viewed his doctorate as a badge that would allow him to strike up conversations with physicians.

Franklin, 48, says his job involved more salesmanship than science. He told doctors that Neurontin was the best drug for a dozen off-label uses, including pain relief, bipolar disease and depression.

‘What I Did Was Wrong’

“Technically, I had responsibility for answering physician questions about all of Parke-Davis’s drugs,” Franklin says. “In practice, my real job was to promote Neurontin for off- label indications heavily -- to the exclusion of just about everything else.”

Franklin, whose wife is a lawyer, says he knew such uses of the drug had no scientific support for effectiveness and safety.

“I was actually undermining their ability to fulfill the Hippocratic oath,” Franklin says, referring to a physician’s pledge to “first, do no harm.”

Franklin says he was horrified when he learned from a doctor that a child had a behavioral outburst at school for the first time after taking Neurontin.

“Don’t we have an obligation to tell physicians about this?” Franklin says he asked his manager, Phil Magistro. His boss tried to reassure him, Franklin says.

‘Total Disregard’

“‘Don’t worry about this stuff,’” he says Magistro told him. “‘It can never get back to us.’”

Franklin was stunned.

“I realized at that moment, looking into his eyes, that there was an absolute total disregard for the patient,” he says.

Magistro, who now works at drug marketing adviser Atom Strategic Consulting LLC in Randolph, New Jersey, didn’t return calls seeking comment.

Franklin saved phone messages from Magistro to his sales team urging them to market Neurontin for off-label uses, including pain relief. During one such call, on May 23, 1996, at 5:48 p.m. in Boston, Magistro told his staff, “You’re supposed to be pushing on Neurontin,” according to a transcript of the tape filed in federal court.

“When we get out there, we want to kick some ass. We want to sell Neurontin on pain,” Magistro said. “All right?”

Quit the Job

After working for Warner-Lambert for three months, Franklin grew concerned about his own liability. He quit the job and talked with Boston attorney Thomas Greene, who helped him file a lawsuit against the company.

Franklin acted as a whistle-blower, suing on behalf of taxpayers to recover money the government paid for illegally promoted drugs. Under federal and state whistle-blower statutes, he stood to collect as much as 30 percent of any settlement the company made with the government.

Franklin had to wait four years -- until 2000 -- before the Justice Department began a criminal investigation. In November 1999, Pfizer made its public offer to buy Warner-Lambert. In January 2000, a federal grand jury in Boston issued subpoenas to Warner-Lambert employees to testify about the marketing of Neurontin.

That March, Warner-Lambert’s annual report disclosed that prosecutors were building a criminal case. Undeterred, Pfizer bought Warner-Lambert in June for $87 billion. It was the third- largest merger in U.S. history.

‘Misleading and in Violation’

A year after the acquisition, the FDA discovered that Neurontin was still being marketed off-label. In a letter to the company on June 29, 2001, the agency wrote that Pfizer’s promotion of the drug “is misleading and in violation of the Federal Food, Drug and Cosmetics Act.”

The agency asked Pfizer to stop such promotions of Neurontin. The FDA said Pfizer had distributed brochures -- known as “slim jims” because they’re small enough to put in a jacket pocket -- improperly claiming that the drug could improve energy levels and memory.

“Immediately discontinue the use of this slim jim and any other promotional material or practices with the same or similar messages,” the FDA wrote.

Pfizer marketed Neurontin off-label after receiving that letter, agency records show. For 2001, Pfizer reported revenue of $1.75 billion from Neurontin sales, making it the company’s fourth-largest-selling drug that year, ahead of impotence pill Viagra, which Neurontin topped for four years.

Marketing Violated Rules

As Neurontin sales soared to $2.27 billion in 2002, the FDA found that Pfizer was improperly claiming that the drug was useful for a broader range of brain disorders than scientific evidence had established.

The agency sent a letter dated July 1, 2002, that said the company’s marketing practices were in violation of FDA rules. It asked Pfizer to stop using misleading promotions. Pfizer reported $2.7 billion in revenue from Neurontin in 2003. Overall, the drug has provided Pfizer with $12 billion in revenue.

In a response to Bloomberg News, Pfizer spokesman Chris Loder said, “Regarding the 2001 and 2002 FDA letters, we do not believe that they were suggestive of any continuing off-label promotion.”

For blowing the whistle on his employer, Franklin collected $24.6 million under the False Claims Act.

Prosecutors Loucks and Sullivan got involved in the case after Franklin filed his suit, relying on information from Franklin and their own investigation. Before 2004, prosecutions for off-label marketing were rare.

‘Everybody Does It’

“Until a couple of these cases became public, companies were probably saying, ‘Everybody does it this way,’” Sullivan says.

Loucks had a track record in off-label prosecutions. He gave up private practice at Choate Hall & Stewart LLP in Boston in 1985 to join the U.S. Attorney’s Office.

In 1994, he negotiated a $61 million settlement with Murray Hill, New Jersey-based C.R. Bard Inc., which pleaded guilty to promoting off-label use of a heart catheter that led to patient deaths.

In 2002, he co-authored, with Carol Lam, “Prosecuting and Defending Health Care Fraud Cases” (BNA Books).

In the January 2004 settlement negotiations with Loucks, Sullivan and two other prosecutors, Pfizer’s lawyers assured the U.S. Attorney’s Office that the company wouldn’t market drugs off-label.

‘Those Promises’

“They asserted that the company understood the rules and had taken steps to assure corporate compliance with the law,” Loucks says. “We remember those promises.”

What Pfizer’s lawyers didn’t tell the prosecutors was that Pfizer was at that moment running an off-label marketing promotion using more than 100 of its salespeople. They were pitching Bextra, a Pfizer sales manager admitted when she pleaded guilty to misbranding a drug on March 30, 2009.

Jeff Kindler, who became Pfizer’s general counsel in 2002, supervised the lawyers who made the promises to prosecutors. By 2004, Kindler increased the compliance budget 12-fold. He became chief executive officer in 2006. In Pfizer’s ethics guide, he says stories about misbehaving companies and executives abound.

“Pfizer truly stands apart,” he says. “I am proud of our record.” On Oct. 1, Kindler was elected to the board of the Federal Reserve Bank of New York. Kindler declined to comment.

Peapack, New Jersey-based Pharmacia & Upjohn Inc. developed Bextra, which was approved by the FDA only for the treatment of arthritis and menstrual discomfort in 2001.

Sales Manager Pleads Guilty

P&U and Pfizer had by then already crafted a joint marketing agreement to sell the drug. In November 2001, Mary Holloway, a Pfizer regional manager for the Northeastern U.S., began illegally training and directing her sales team to market Bextra for the relief of acute pain, Holloway admitted in a March 2009 guilty plea.

On Dec. 4, 2001, Pfizer executives sent Holloway a copy of a nonpublic letter from the FDA to the company. The agency had denied Pfizer’s application to market Bextra for acute pain. Clinical trials had shown Bextra could cause heart damage and death.

Pfizer bought Pharmacia & Upjohn in April 2003. From 2001 to the end of 2003, P&U, first as an independent company and then as a unit of Pfizer, paid physicians more than $5 million in cash to lure them to resorts, where salespeople illegally pitched off-label uses for Bextra, P&U admitted in its Sept. 2 guilty plea.

‘Golf, Massages’

“Pharmacia paid targeted physicians both airfare and two to three days’ accommodations at lavish resorts in the Bahamas, Virgin Islands and across the United States and further entertained these physicians with golf, massages and other recreation activities,” according to prosecutors’ findings.

In her guilty plea, Holloway said her team had solicited hospitals to create protocols to buy Bextra for the unapproved purpose of acute pain relief. Her representatives didn’t mention the increased risk of heart attacks in their marketing.

They told doctors that side effects were no worse than those of a sugar pill, Holloway admitted in her guilty plea.

In 2003, Holloway reported her unit’s off-label promotions of Bextra up the corporate ladder at Pfizer, according to a pre- sentencing memo to the judge written by Robert Ullmann, Holloway’s attorney. Top managers didn’t attempt to halt the illegal conduct, the memo said.

“Corporate tracked this information, and at no time did it inform Ms. Holloway that any of the reported protocols were inappropriate,” he wrote. “Instead, the instruction was to get more protocols.”

Blockbuster Status

By the end of 2004, Bextra reached blockbuster status, with annual sales of $1.29 billion. Holloway promoted Bextra until the FDA asked Pfizer in April 2005 to pull it from the market for all uses, evidence in her case shows.

The agency concluded that the drug increased the risk of heart attacks, chest infections and strokes in cardiac surgery patients. In June 2009, Holloway, 47, was sentenced to two years on probation and fined $75,000. She didn’t return phone calls seeking comment.

Ronald Rainero, a Pfizer district sales manager and employee for more than 20 years, says he was responsible for promoting Bextra in New York from 2001 to 2005. In September 2007, Rainero, 47, began cooperating with federal prosecutors on the Bextra case.

Hotel Meetings

He says he met monthly with his fellow managers at a Hilton hotel in Staten Island, New York, to discuss sales methods of promoting Bextra off-label. As a whistle-blower, Rainero was awarded $9.3 million as part of the September settlement.

In the same time period that Pfizer was marketing Bextra off-label, the company’s sales force was promoting another drug, Zyvox, improperly, Pfizer admitted at the time of its September plea agreement.

Zyvox was approved in 2000 by the FDA for treating MRSA- caused pneumonia and skin infections. Raniero told federal prosecutors that Pfizer began the Zyvox campaign in 2001. The company admitted to falsely claiming that the drug was better than other medications for treating MRSA pneumonia.

Pfizer told doctors to use Zyvox rather than vancomycin, a generic antibiotic that cost $18 a day. Pfizer sold Zyvox for about $150 a day. A table on page 30 of a 35-page fact book produced by Pfizer for Zyvox says the drug is less effective than vancomycin for MRSA pneumonia.

‘Misleading Promotion’

On July 20, 2005, the FDA sent a letter to Hank McKinnell, then Pfizer’s CEO, saying, “Your misleading promotion of Zyvox, and in particular your unsubstantiated implied claims regarding its superiority to vancomycin, poses serious health and safety concerns.”

The agency ordered the company to stop the promotion. In response, Pfizer told the FDA it would stop saying Zyvox was more effective against MRSA pneumonia than vancomycin.

Despite its 2005 pledge to the FDA, Pfizer continued to tell hospitals and doctors that Zyvox would save more lives than vancomycin, the company admitted in the September settlement.

By 2007, the criminal and civil cases against Pfizer, its employees and its subsidiaries had started to mount. The tally of drugs cited by federal prosecutors for off-label promotion reached six by 2009. In April 2007, P&U pleaded guilty to a felony charge of offering a $12 million kickback to a pharmacy benefit manager.

$2.2 Billion in Penalties

Pfizer paid a criminal fine of $19.7 million. Thomas Farina, a Pfizer district sales manager, was convicted in federal court in March 2009 for destroying records during the Bextra investigation. Farina, 42, was sentenced to three years on probation, including six months of home confinement. He didn’t return calls seeking comment.

Pfizer itself was called to account on Sept. 2, when it agreed to pay the $2.2 billion in fines and penalties. P&U pleaded guilty to a felony charge of misbranding Bextra with the intent to defraud. After the settlement, Pfizer general counsel Amy Schulman said the company had learned its lesson.

“We regret certain actions we’ve taken in the past,” she said. “Corporate integrity is an absolute priority for Pfizer.”

One reason drug companies keep breaking the law may be because prosecutors and judges have been unwilling to use the ultimate sanction -- a felony conviction that would render a company’s drugs ineligible for reimbursement by state health programs and federal Medicare.

“It’s potentially a death sentence for a drug company,” prosecutor Sullivan says.

Fig Leaf

A legal fig leaf allows a parent company to continue to participate in government programs even after its subsidiary has pleaded guilty.

Pfizer maintains its good standing with such agencies because its subsidiaries, Warner-Lambert and P&U, and not the corporation itself, entered the guilty pleas to felony charges.

A felony conviction of a pharmaceutical giant could lead to disaster for shareholders, Loucks says, adding that’s a step that may have to be taken for repeat offenders.

“I think it’s something the trigger will get pulled on,” he says from his ninth-floor office in the federal courthouse, with a sweeping view of Boston Harbor. “It’s just a question of when.”

At Pfizer’s Pharmacia sentencing on Oct. 16., U.S. District Court Judge Douglas Woodlock said companies don’t appear to take the law seriously.

“It has become something of a cost of doing business for some of these corporations, to shed their skin like certain animals and leave the skin and move on,” he said.

Eli Lilly

Lilly’s rap sheet goes back to 1985. That’s when the company pleaded guilty to 25 federal misdemeanor charges related to its misbranding of Oraflex, an arthritis drug.

Lilly stopped selling the drug four months after U.S. sales began in 1982, following the company’s failure to tell the FDA about illnesses and deaths tied to the medication. Lilly paid a $25,000 fine.

Twenty years later, in 2005, Lilly paid $36 million in a guilty plea to one federal misdemeanor for off-label marketing of Evista, a drug the FDA had approved for bone strengthening.

In 1997, the agency had rejected Lilly’s application to market the drug to reduce the risk of breast cancer. Yet beginning the next year, Lilly adopted an Evista marketing plan that included a seminar with doctors designed to appeal to women’s breast cancer concerns, Lilly admitted in its 2005 guilty plea.

In 2007, the FDA approved Evista for preventing breast cancer in two limited groups.

Back in Court

In January 2009, Lilly was back in federal court. Prosecutors in Philadelphia accused the company of earning hundreds of millions of dollars by illegally promoting its schizophrenia drug Zyprexa for the unapproved treatment of dementia from 1999 to at least 2003.

In 2001, Lilly’s senior management decided not to seek FDA approval for Zyprexa to treat dementia because of what they viewed as mixed results in clinical trials and safety risks, according to admissions by Lilly in its 2009 guilty plea. In its marketing, Lilly promoted the drug as effective.

Zyprexa has been Lilly’s best-selling drug for the past decade.

“Eli Lilly undertook this illegal off-label promotion for its own financial gain despite the potential risk to patients’ health and lives,” prosecutors wrote in their sentencing memo.

Lilly Chairman and CEO John Lechleiter said after the settlement that the company was devoted to acting responsibly.

‘Deeply Regret’

“We deeply regret the past actions covered by the misdemeanor plea,” he said. “Doing the right thing is nonnegotiable at Lilly.”

In a written response to questions from Bloomberg News, Lilly said, “Lilly entered into a very narrow guilty plea. Even though the company disagrees with and does not admit to the allegations, Lilly agreed to settle the dispute.”

Lilly paid $1.42 billion for a fine and penalties in the January settlement with federal and state governments. That included the largest criminal fine in U.S. history -- until Pfizer pleaded guilty in September.

The Justice Department could have charged Lilly with a felony. Prosecutors decided that it wouldn’t be fair to innocent Lilly employees, shareholders and pensioners to potentially shut down the company, according to the sentencing memo.

‘All the Factors’

“The government considered all the factors in its decision,” prosecutors wrote. “Those factors included other persons not proven personally culpable.”

Federal regulators have detected a similar pattern of dishonesty by other pharmaceutical firms. Schering-Plough Corp. drug salesmen pitched off-label uses of a cancer drug called Temodar at the American Society of Clinical Oncology’s annual conference in San Francisco in May 2001.

Schering-Plough representatives said Temodar compared favorably to a placebo in clinical trials for the off-label uses and was approved by the FDA for first-line use in treating brain tumors.

An FDA employee attending the conference took note. The next month, the FDA accused Schering of lying.

There had been no such clinical trials and the agency had not approved Temodar as the salespeople had claimed, the FDA said in a June 28, 2001, letter to Mary Jane Nehring, Schering’s senior director of marketed products. The agency ordered the company to immediately cease illegal promotion of Temodar.

Kenilworth, New Jersey-based Schering-Plough was quick to respond. On July 12, 2001, it wrote back to the FDA, assuring regulators that the San Francisco activity was an isolated incident.

‘Certainly Inconsistent’

“It was certainly inconsistent with the direction provided by the home office,” the drug company wrote, according to prosecutor’s records.

The FDA told Schering-Plough three weeks later that it had closed its investigation.

Schering-Plough didn’t stop pitching the drug for unapproved uses. At the direction of top management, Schering ordered widespread off-label marketing of Temodar and Intron A, another cancer drug, until December 2003, the company admitted in an August 2006 guilty plea.

Schering, which agreed in March to be acquired by Merck & Co., earned a pre-tax profit of $124.2 million from the illegal sales after promising the FDA in 2001 it would stop marketing for off-label uses, the company admitted.

Schering-Plough pleaded guilty in August 2006 to conspiring to make false statements to the FDA. The company agreed to pay $435 million to settle the case.

‘Upsetting to Me’

U.S. District Court Judge Patti Saris, who had presided over the Neurontin whistle-blower case before the Pfizer probe, accepted Schering’s plea in her Boston courtroom in January 2007. She expressed dismay with the drug industry.

“It’s been upsetting to me how many of the big pharmaceutical companies have engaged in what I view as clearly illegal behavior in terms of off-label marketing,” she said. “It almost seems as if the pharmaceutical companies said ‘Yeah, yeah, yeah’ to the FDA and then went and did it anyway.”

Brent Saunders, a Schering-Plough senior vice president, said after the settlement that his company had made great progress in putting integrity at the center of its work.

“With this agreement, we are putting issues from the past behind us,” he said. Schering declined to comment further.

As prosecutors continue to uncover patterns of deceit in off-label marketing by pharmaceutical companies, millions of patients across the nation remain in the dark. Doctors often choose the medications based on dishonest marketing by drug company salesmen.

‘A Morass’

“It’s a morass of undifferentiated information out there,” Public Citizen’s Lurie says. “And the doctors, let alone patients, aren’t able to distinguish the good from the bad.”

One thing all people should do, Lurie says, is ask whether their prescriptions are for FDA-approved uses, and if not, whether strong evidence supports using the drug, particularly if it can be dangerous.

Loucks says that putting an end to the criminal off-label schemes by the pharmaceutical industry is more difficult. As drugmakers repeatedly plead guilty, they’ve shown they’re willing to pay hundreds of millions of dollars in fines as a cost of generating billions in revenue.

The best hope, Loucks says, is that drug companies actually honor the promises they keep making -- and keep breaking -- to obey the law of the land.

To contact the reporter on this story: David Evans in Los Angeles at davidevans@bloomberg.net