Tag Archives: conflict of interest

Mental Health First Aid: Another Psychiatric Expansionist Tool

On December 25, 2016, the Baltimore Sun published an excellent article titled Drug companies prey on children, by Patrick D. Hahn, PhD.  Dr. Hahn is an affiliate professor of biology at Loyola University, Maryland.  Here are some quotes:

“I recently attended Youth Mental Health First Aid Training at a local public school. It was an eye-opening experience.”

“Youth Mental Health First Aid Training, sponsored by the National Council for Behavioral Health, is intended to enable teachers, parents and others in contact with young people to identify potential ‘mental illnesses’ in order to facilitate early detection and treatment by our mental health care system. My fellow attendees were surprisingly open about their own experiences with that system. One mentioned that her son became manic after being diagnosed for ADHD. Another said that both she and her roommate became bipolar after being diagnosed for depression. Neither our facilitators nor anyone else present pointed out that mania and bipolar disorder are toxic effects of medications commonly prescribed for ADHD and depression.”

“Our training manual didn’t say anything about this either, although it did claim that depression is caused by a deficiency of serotonin — a fable that by now has become as discredited as the phlogiston theory of chemistry. It also stated that mental health interventions are ‘evidence-based’ and ‘scientifically tested’ — neglecting to mention that much of that evidence is put forth by drug companies who have a fiduciary duty to do everything they can to maximize sales of their products.”

“So is all this a scheme to push more drugs to more kids? The 2013/2014 annual report for the National Council for Behavioral Health, titled ‘A Legacy of Excellence and Impact,’ gives us a hint. It lists the organization’s supporters as including the Pharmaceutical Research and Manufacturers of America (PhRMA) along with no fewer than 12 different drug companies. Would these folks be ponying up the cash if they weren’t confident this program would increase sales? And do the parents and teachers who attend the council’s training program — no doubt with the best intentions in the world — realize that they are essentially sitting through an eight-hour infomercial bought and paid for by the drugmakers?”

“One out of 13 American children between the ages of 6 and 17 has taken a psychotropic medication within the last six months, according to the Centers for Disease Control. Meanwhile, youth suicide rates are at their peak going back at least as far back as 1999, while the number of children receiving disability benefits for mental illness is at an all-time high.”

Please take a look at Dr. Hahn’s article, and pass it on.  Mental Health First Aid is not a good thing.  Rather, it is just another psychiatric expansionist tool.

MENTAL HEALTH FIRST AID

For readers who are not familiar with the term, Mental Health First Aid, according to its own website, is “…an 8-hour course that teaches you how to identify, understand and respond to signs of mental illnesses and substance use disorders.”

From its FAQ page:

“The evidence behind the program demonstrates that it does build mental health literacy, helping the public identify, understand, and respond to signs of mental illness.”

Incidentally, I Googled the term “mental health literacy” and got 28.8 million results!  There’s also a Wikipedia article on mental health literacy.  Here’s a quote from the opening paragraph:

Mental health literacy has been defined as ‘knowledge and beliefs about mental disorders which aid their recognition, management or prevention. Mental health literacy includes the ability to recognize specific disorders; knowing how to seek mental health information; knowledge of risk factors and causes, of self-treatments, and of professional help available; and attitudes that promote recognition and appropriate help-seeking.1‘”

So mental health literacy doesn’t just mean the acquisition of some information and skills; it also means accepting the psychiatric hoax:  “attitudes that promote recognition and appropriate help-seeking”.  The goal is not just the dissemination of psychiatry-friendly information, but also the active conversion of skeptics to the psychiatric cause.

Reference # 1 in the above quote refers to Jorm et al “Mental health literacy”: a survey of the public’s ability to recognise mental disorders and their beliefs about the effectiveness of treatment, Med J Aust. 1997 Feb 17;166(4):182-6.  The survey in question was conducted in Australia in 1995 and sheds particular light on the present discussion.  Here’s the abstract of the article:

“OBJECTIVES:
To assess the public’s recognition of mental disorders and their beliefs about the effectiveness of various treatments (‘mental health literacy’).

DESIGN:
A cross-sectional survey, in 1995, with structured interviews using vignettes of a person with either depression or schizophrenia.

PARTICIPANTS:
A representative national sample of 2031 individuals aged 18-74 years; 1010 participants were questioned about the depression vignette and 1021 about the schizophrenia vignette.

RESULTS:
Most of the participants recognised the presence of some sort of mental disorder: 72% for the depression vignette (correctly labelled as depression by 39%) and 84% for the schizophrenia vignette (correctly labelled by 27%). When various people were rated as likely to be helpful or harmful for the person described in the vignette for depression, general practitioners (83%) and counsellors (74%) were most often rated as helpful, with psychiatrists (51%) and psychologists (49%) less so. Corresponding data for the schizophrenia vignette were: counsellors (81%), GPs (74%), psychiatrists (71%) and psychologists (62%). Many standard psychiatric treatments (antidepressants, antipsychotics, electroconvulsive therapy, admission to a psychiatric ward) were more often rated as harmful than helpful, and some nonstandard treatments were rated highly (increased physical or social activity, relaxation and stress management, reading about people with similar problems). Vitamins and special diets were more often rated as helpful than were antidepressants and antipsychotics.

CONCLUSION:
If mental disorders are to be recognised early in the community and appropriate intervention sought, the level of mental health literacy needs to be raised. Further, public understanding of psychiatric treatments can be considerably improved.”

So, in 1995, the general public in Australia, as represented by the sample of 2031 individuals in this study, had some interesting views concerning psychiatry.

  1. They rated GP’s and counselors as more helpful than psychiatrists and psychologists for problems of “depression” and “schizophrenia”.
  1. They rated many “standard psychiatric treatments” (antidepressants, neuroleptics, electric shocks, and psychiatric wards) harmful, more often than helpful.
  1. They rated some “nonstandard treatments” (increased physical or social activity, relaxation, stress management, reading about people with similar problems) highly.
  1. They rated vitamins and special diets helpful more often than antidepressant and neuroleptic drugs.

At the risk of stating the obvious, those of us on this side of the issue would consider the general public’s beliefs, as reflected in this survey, to be accurate, and grounded in common sense.  But from the aspect of psychiatry – and particularly psychiatry’s expansionist agenda – these findings are cause for particular concern.  And so, as the authors state:  “…the level of mental health literacy needs to be raised…”

Here’s an interesting quote from the study’s Introduction:

“The lifetime risk of developing a mental disorder is so high (nearly 50%)2 that almost the whole population will at some time have direct experience of such a disorder, either in themselves or in someone close. A high public level of mental health literacy would make early recognition of and appropriate intervention in these disorders more likely.”

Incidentally, the survey was conducted by the Australian Bureau of Statistics, presumably at public expense.

Three years later, Dr. Jorm, the lead author, and his wife Betty Kitchener, founded Mental Health First Aid.  According to his biography on the University of Melbourne site, Dr. Jorm is a highly cited mental health researcher whose work “…focuses on building the community’s capacity for prevention and early intervention with mental disorders.”

The MHFA program spread rapidly in Australia, and by 2015, 350,000 people had received the training.

And Dr. Jorm has been busy promoting mental health literacy in other venues.  In 2000, he published a paper in the British Journal of Psychiatry, the stated aims of which were:

“To introduce the concept of mental health literacy to a wider audience, to bring together diverse research relevant to the topic and to identify gaps in the area.”

And in 2012, he and Nicola Reavley published a paper Public recognition of mental disorders and beliefs about treatment: changes in Australia over 16 years, also in the British Journal of Psychiatry.  The conclusions of this paper were:

“Although beliefs about effective medications and interventions have moved closer to those of health professionals since the previous surveys, there is still potential for mental health literacy gains in the areas of recognition and treatment beliefs for mental disorders. This is particularly the case for schizophrenia.”

THE SCOPE OF THE MENTAL HEALTH FIRST AID PROGRAM

Here’s another quote from MHFA’s FAQ page:

“Mental Health First Aid is intended for all people and organizations that make up the fabric of a community. The course is presented to chambers of commerce, professional associations, hospitals, nursing homes, rotary clubs, parent organizations, social clubs, and other groups. Professionals who regularly interact with a lot of people (such as police officers, human resource directors, and primary care workers), school and college leadership, faith communities, friends and family of individuals with mental illness or addiction, or anyone interested in learning more about mental illness and addiction should get trained.”

And so the tentacles of psychiatric destruction, disempowerment, and, ultimately, despair, are spread to all parts and segments of our society, and people of all ages and all walks of life are shoveled indiscriminately into the insatiable maw of psychiatric dependency and premature death.

Mental Health First Aid (USA) lists on its website 109 organizations across the US (including 45 NAMI chapters) that offer MHFA training.

MHFA AND THE APA

Not surprisingly, the APA has enthusiastically endorsed the program.  Here are some quotes from Mental Health First Aid:  Training for Communities and Families, which you can find on the APA website:

“Mental Health Fist Aid (MHFA) is an eight-hour, in-person training that teaches how to help a person struggling with a mental illness or in a crisis. It provides a basic understanding of mental illness and addiction, signs of addiction and mental illness, the impact of mental and substance use disorders, what helps individuals experiencing these challenges get well and local resources for help.”

Note the emphasis on “mental illness” and “mental disorders”, and the notion that individuals “experiencing these challenges” need to “get well” by accessing “local resources for help”.

“Trainees are taught a five-step action plan and how to apply it in a variety of situations such as helping someone experiencing psychosis, engaging with someone who may be suicidal, or assisting an individual who has overdosed. The training uses role play and demonstrations to convey the information.”

“Five-Step Action Plan – ALGEE

  1. Assess for risk of suicide or harm
  2. Listen nonjudgmentally
  3. Give reassurance and Information
  4. Encourage appropriate professional help
  5. Encourage self-help and other support strategies”

Note:  “encourage appropriate professional help”, conveniently ignoring the reality that the most common form of “professional help” (psychiatric drugging) is causally implicated in the creation of the problems.

“More than 250,000 people have been trained in Mental Health First Aid in the U.S. by 5,200 certified instructors. Twenty-one states have legislation to support Mental Health First Aid, and federal grants support training in some communities.”

So American psychiatry has effectively recruited 250,000 volunteer sales reps, and has managed to get state and federal money to support this enterprise.

“A recent national study of the training concluded that MHFA improves confidence about being able to recognize someone who may be dealing with a mental health problem or crisis and to actively and compassionately listen to someone in distress. Researchers surveyed more than 35,000 people who had completed the training for the study published in the APA journal Psychiatric Services.”

The study mentioned is Crisanti AS, Luo L, McFaul M, et al. Impact of Mental Health First Aid on confidence relation to mental health literacy: a national study with a focus on race-ethnicity. Psychiatric Services in Advance. Published online Nov. 2, 2015.

Here’s the abstract:

“OBJECTIVE:
Low mental health literacy (MHL) is widespread in the general population and even more so among racial and ethnic minority groups. Mental Health First Aid (MHFA) aims to improve MHL. The objective of this study was to determine the impact of MHFA on perceptions of confidence about MHL in a large national sample and by racial and ethnic subgroup.

METHODS:
The self-perceived impact of MHFA on 36,263 people who completed the 12-hour training and a feedback form was examined.

RESULTS:
A multiple regression analysis showed that MHFA resulted in high ratings of confidence in being able to apply various skills and knowledge related to MHL. Perceived impact of MHFA training differed among some racial and ethnic groups, but the differences were small to trivial.

CONCLUSIONS:
Future research on MHFA should examine changes in MHL pre-post training and the extent to which perceived increases in MHL confidence among trainees translate into action.”

In other words, people who take the Mental Health First Aid course expressed confidence that they could apply the skills and knowledge acquired to actual situations.  The implication is that this is important because “Low mental health literacy (MHL) is widespread in the general population and even more so among racial and ethnic minority groups.”

Note that the term “mental health literacy” has now been reified into a desirable commodity, the lack of which can be identified, measured, decried, researched, funded, etc., in the interests of bringing more and more people into psychiatry’s insatiable clutches.  Mental health literacy means the extent to which one has bought the psychiatric hoax.  Those of us who are active in the anti-psychiatry movement are, of course, by implication, mental health illiterates.

There are absolutely no limits to psychiatry’s expansionist agenda.  Despite the well-established destructiveness of their “treatments”, they will never voluntarily curtail their relentless drive for more victims.

And they will not commission, or even call for, a formal, comprehensive study to examine the now blatantly obvious link between psychiatric drugs and the murder-suicides that have become commonplace in our communities.  Psychiatry is intellectually and morally bankrupt.  They have no valid response to their critics, but instead resort to spin and tawdry marketing tactics to shore up their crumbling sand castle.  But just as the tide cleans the foreshore, so the light of logic and truth, and the outspoken protests of its survivors, will one day wash the world of the blight known as psychiatry.

The Mental Health Reform Act of 2016 (SB 2680) Would Be a Huge Step Backwards

On July 6, HB 2646 (the Tim Murphy Bill) passed the US House and was sent to the Senate.

At the present time, a related bill is working its way through the Senate.  This is SB 2680, The Mental Health Reform Act 2016.  It is sponsored by Lamar Alexander (R-TN), Patty Murray (D-WA), Bill Cassidy (R-LA), Chris Murphy (D-CT), David Vitter (R-LA), and Al Franken (D-MN).  The wording of the bill was finalized in March of this year, and it passed out of committee on March 16.

There is a good measure of bi-partisan support for this bill in the Senate, and if it makes it to the floor it could pass.  If that were to happen, it would likely be reconciled with the Tim Murphy House resolution, and a reconciled version would be enacted.

SB 2680 purports to provide desperately needed help to suffering Americans but is in reality a thinly-disguised tool to expand the scope of psychiatric “care”, with all the drugging, death, damage, and destruction that this entails.

On March 16, 2016, the Committee on Health, Education, Labor, and Pensions issued a press release titled:  The Mental Health Reform Act of 2016 will help Americans suffering from mental health and substance use disorders.  Here are some quotes, interspersed with my comments and observations.

“The Senate health committee today passed legislation to help address the country’s mental health crisis and help ensure Americans suffering from mental illness and substance use disorders receive the care they need.”

Note the term “mental health crisis”.  There is indeed a crisis in the mental health business.  The crisis derives from psychiatry’s spurious and self-serving premise that all significant problems of thinking, feeling, and/or behaving are brain illnesses that are correctable by psychiatric drugs.  This false premise, avidly promoted by pharma, is the cornerstone of the psychiatric-pharmaceutical industry, and is the primary reason that psychiatric drug use in America has reached epidemic proportions.

The fact that these so-called illnesses are so vaguely defined makes it easy for pharma-psychiatry to rope in new recruits.  But the maw of greed can never be satisfied, and pharma-psychiatry continues to lobby for more.  Every undrugged person is money down the drain!

For decades, psychiatry has been inventing new “illnesses” and liberalizing the criteria for others, and it is clear that their objective in all this is to make their so-called mental illnesses as prevalent as the common cold:  everyone gets one from time to time, and psychiatry has “safe and effective treatments”.  There’s no need to suffer – just take a pill or a high-voltage electric shock to the brain.  And keep coming back!

Back to the press release:

“‘One in five adults in this country suffers from a mental illness, and nearly 60 percent aren’t receiving the treatment they need,’ said Senate health committee Chairman Lamar Alexander (R-Tenn.).”

It is a logical and mathematical axiom that one can’t quantify what one can’t define.  But even if we set aside the inanity of these oft-touted statistics, it is clear that vast numbers of Americans who could get a “diagnosis” and a prescription for pills at their local mental health center, choose, wisely, I suggest, not to avail themselves of this “service”.  To Senators Alexander, Murray, Cassidy, Murphy, Vitter, and Franken, however, all of whom, incidentally, have received campaign money from the pharmaceuticals/health products industry, this is a national tragedy – a crisis, no less, that has to be corrected through legislative action.

“‘This bill will help address this crisis by ensuring our federal programs and policies incorporate proven, scientific approaches to improve care for patients.'”

“Proven, scientific approach” means more pharma-funded psychiatric research, with ever more opportunities for over-stated conclusions and even out-and-out fraud.

Senator Murray points out that the bill, if enacted, “…would help expand access to quality care, and make sure that patients receive coordinated mental and physical health care.”

Note again the emphasis on expanding care.  Also note the promotion of co-ordination with physical (i.e. real) medicine; read:  a mental health liaison worker in every GP’s office.  The APA has been pushing this idea for years.  The idea is that one goes to see one’s GP for a bad cough, is “screened” for mental health issues, and comes away with an antibiotic for the cough and an antidepressant for some vague psychosocial concerns.

The press release continues in the same vein.  All the old chestnuts are there, e.g.:

“This bill is an important step in the road to recovery for the 44 million Americans who suffer from a serious mental illness.”

“…our broken mental health care system…”

“…we allow those with mental illness to fall through the cracks.”

“…families struggling to get a loved one the help they need.”

“…prevent suicide…”

“…provide mental health awareness for teachers and others…”

“…evidence-based approaches…”

etc.

DISCUSSION

SB 2680 is littered with platitudes, and for this reason, there is a danger that many of its provisions might be seen as benign, and even desirable.

For instance, the bill calls for the identification of

“…strategic priorities, goals, and measurable objectives for mental and substance use disorder activities and programs operated and supported by the Administration, including priorities to prevent or eliminate the burden of mental illness and substance use disorders;”

and

“…to improve services for individuals with a mental or substance use disorder…”

and

“…ensure that programs provide, as appropriate, access to effective and evidence-based prevention, diagnosis, intervention, treatment, and recovery services…”

etc.

All of these proposals seem positive and helpful, but the bill is solidly rooted in psychiatry’s spurious medical model.  Psychiatric concepts and language permeate the text.  The term “mental illness” is routinely used as if it had the same ontological significance as real illness.

To convey the general tone and thrust of the bill, here’s the full text of Sec 502, which pertains to child psychiatry:

SEC. 502. TELEHEALTH CHILD PSYCHIATRY ACCESS GRANTS.

(a) In General.—The Secretary of Health and Human Services (referred to in this section as the “Secretary”), acting through the Administrator of the Health Resources and Services Administration and in coordination with other relevant Federal agencies, may award grants through existing health programs that promote mental or child health, including programs under section 330I, 330K, or 330L of the Public Health Service Act (42 U.S.C. 254c-14, 254c-16, 254c-18), to States, political subdivisions of States, and Indian tribes and tribal organizations (for purposes of this section, as defined in section 4 of the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450b)) to promote behavioral health integration in pediatric primary care by—”

Translation:  The Federal Government may award grants to promote the embedding of psychiatric concepts and practices into pediatric primary care by:

“(1) supporting the development of statewide or regional child psychiatry access programs; and

 (2) supporting the improvement of existing statewide or regional child psychiatry access programs

(b) Program Requirements.—

(1) IN GENERAL.—To be eligible for funding under subsection (a), a child psychiatry access program shall—

(A) be a statewide or regional network of pediatric mental health teams that provide support to pediatric primary care sites as an integrated team;

(B) support and further develop organized State or regional networks of child and adolescent psychiatrists to provide consultative support to pediatric primary care sites;”

Note:  “networks” of psychiatrists advising and supporting pediatricians!  What kind of advice do you think these networks of psychiatrists will provide?

“(C) conduct an assessment of critical behavioral consultation needs among pediatric providers and such providers’ preferred mechanisms for receiving consultation and training and technical assistance;

(D) develop an online database and communication mechanisms, including telehealth, to facilitate consultation support to pediatric practices;

(E) provide rapid statewide or regional clinical telephone consultations when requested between the pediatric mental health teams and pediatric primary care providers;

(F) conduct training and provide technical assistance to pediatric primary care providers to support the early identification, diagnosis, treatment, and referral of children with behavioral health conditions and co-occurring intellectual and other developmental disabilities;”

What kind of training do you think these access programs will be providing to pediatricians?  Facile “diagnostic” checklists?  Treatment guidelines that recommend neuroleptic drugs for 3-year-olds who display temper tantrums?  The thinly-hidden agenda here is to erode whatever resistance remains among pediatricians to psychiatric orthodoxy, and bring them on board the great psychiatric drugging bonanza.

“(G) inform and assist pediatric providers in accessing child psychiatry consultations and in scheduling and conducting technical assistance;

(H) assist with referrals to specialty care and community and behavioral health resources; and

(I) establish mechanisms for measuring and monitoring increased access to child and adolescent psychiatric services by pediatric primary care providers and expanded capacity of pediatric primary care providers to identify, treat, and refer children with mental health problems.”

In other words, the Feds will be checking to make sure that they’re getting value for their money in the form of more children drugged.

“(2) PEDIATRIC MENTAL HEALTH TEAMS.—In this subsection, the term “pediatric mental health team” means a team of case coordinators, child and adolescent psychiatrists, and a licensed clinical mental health professional, such as a psychologist, social worker, or mental health counselor. Such a team may be regionally based.

(c) Applications.—A State, political subdivision of a State, Indian tribe, or tribal organization that desires a grant under this section shall submit an application to the Secretary at such time, in such manner, and containing such information as the Secretary may require, including a plan for the comprehensive evaluation and the performance and outcome evaluation described in subsection (d).

(d) Evaluation.—A State, political subdivision of a State, Indian tribe, or tribal organization that receives a grant under this section shall prepare and submit an evaluation to the Secretary at such time, in such manner, and containing such information as the Secretary may reasonably require, including a comprehensive evaluation of activities carried out with funds received through such grant and a performance and outcome evaluation of such activities.

(e) Access To Broadband.—In administering grants under this section, the Secretary may coordinate with other agencies to ensure that funding opportunities are available to support access to reliable, high-speed Internet for providers.

(f) Matching Requirement.—The Secretary may not award a grant under this section unless the State, political subdivision of a State, Indian tribe, or tribal organization involved agrees, with respect to the costs to be incurred by the State, political subdivision of a State, Indian tribe, or tribal organization in carrying out the purpose described in this section, to make available non-Federal contributions (in cash or in kind) toward such costs in an amount that is not less than 20 percent of Federal funds provided in the grant.

The meaning and intent of Sec 502 is absolutely clear:  if this legislation passes, Congress is going to pour money and resources into providing more psychiatric care to children.

And how do psychiatrists provide care for children?  They drug them.

THE EMPIRE IS FIGHTING BACK

In the past ten years or so, opposition to psychiatry’s medicalization of virtually every human problem has been growing.  As the venerable and prestigious psychiatric leader Jeffrey Lieberman, MD, has lamented on more than one occasion, psychiatry is the only medical speciality that has its own anti group.  And of course, as we all know, there are very good reasons for this.

We also know that American psychiatry as a whole has been extraordinarily unreceptive to any kind of criticism.  Indeed, their response has been to double down – to assert with increasing vigor that their concepts are sound, their research valid, and their practices helpful and benign.

They have also hired a renowned PR firm and have been lobbying hard in political circles.  SB 2680 and the Tim Murphy House bill are the result of these endeavors.

This is the hidden face of psychiatry, using the legal machinery to push its pernicious concepts and practices deeper and deeper into the lives and institutions of the American people, with increasingly disastrous results.

Incidentally, the sponsors of SB 2680 received the following sums of money from the pharmaceutical/health products industry during the current election cycle (source: OpenSecrets.org):

            Lamar Alexander        $452,548

            Patty Murray               $542,778

            Bill Cassidy                 $234,502

            Chris Murphy              $121,876

            Al Franken                  $131,088

            David Vitter                   $7,850

If you live in the US, please ask your Senators to oppose SB 2680.  Tell them that we don’t need any more psychiatric drugging, particularly of our children!

My Response To Dr. Pies

In the October 2015 issue of the Behavior Therapist (pages 206-213), Jeffrey Lacasse, PhD, and Jonathan Leo, PhD, published an article titled Antidepressants and the Chemical Imbalance Theory of Depression: A Reflection and Update on the Discourse,

I thought the article had particular merit, and I drew attention to it in a post dated November 2.  The post, More on the Chemical Imbalance Theory, was also published on Mad in America.

In that post, I quoted a number of passages from the Behavior Therapist article, including:

“When our physicians are educating us, we prefer they not tell us any lies, white or otherwise.  Unfortunately, characterizing the chemical imbalance metaphor as a ‘little white lie’ communicates a paternalistic, hierarchical approach that sounds suspiciously like the days of medicine that we thought we had left behind.  It’s a ‘little white lie’ if you’re a psychiatrist; if you’re a confused, vulnerable depressed person who agrees to take an SSRI after hearing it, you might not consider it so little.  After all, if your trusted physician tells you that you have a chemical imbalance in your brain that can be corrected with medication, not doing so sounds foolish, if not scary (Lacasse, 2005).  How many patients with reservations about SSRIs have agreed to take medication after being told this ‘little white lie’?”

and

“Pies blames the drug companies for running misleading advertisements about chemical imbalance, belatedly admits he should have said something sooner, but fails to mention that he was paid to help them promote their products at the time the advertisements were running.”

On November 5, I received the following email, forwarded from Mad In America:

Message sent by: Ronald Pies MD

Message:Dear Mr. Cole:

Philip Hickey\’s blog, \”More on the Chemical Imbalance Theory\”—posted on your website—references a recent paper by Lacasse & Leo (\”Antidepressants and the Chemical Imbalance Theory of Depression\”) which contains incorrect and misleading information re: my views, as well as an unsupported claim re: supposed “conflicts of interest”  Lacasse & Leo impute to me. These misstatements by Lacasse & Leo are, unfortunately, repeated in Hickey\’s blog.  This is unacceptable and must be publicly corrected. In brief, Lacasse and Leo’s misrepresentations are as follows:

1.  They misattribute the phrase “little white lie” to me, with regard to the so-called “chemical imbalance theory.” In reality, this unfortunate phrase was originally used by Mr. Robert Whitaker in an interview with Bruce Levine. The link is: http://brucelevine.net/psychiatry-admits-its-been-wrong-in-big-ways-but-can-it-change-a-chat-with-robert-whi/

In the article I subsequently wrote, cited by Lacasse & Leo (http://www.medscape.com/viewarticle/823368), my use of that phrase was in direct reference to Whitaker’s interview and to his own choice of words. I made this clear as far back as April, 2014, in a comment I posted beneath my Medscape article (available online). Careful scholars would surely have observed this and not falsely attributed Whitaker\’s phrase to me. The Medscape article has since been corrected.

2.  Citing information properly disclosed by me over a decade ago, Lacasse & Leo allege that I was “paid to help [pharmaceutical companies] promote their products…” This is categorically false. The allegation by Lacasse & Leo was not based on any direct knowledge of my professional or contractual arrangements dating back to 2003. Never, at any time, have I accepted any monies from pharmaceutical companies (or anyone else) with the intent or purpose of promoting their products. Nor have I ever had any ongoing financial relationships with any pharmaceutical companies.

A detailed rejoinder to Lacasse & Leo will appear in the winter issue of \”The Behavior Therapist,\” where the Lacasse & Leo article originally appeared. However, I respectfully request that you run a correction on your website as soon as possible; e.g., by posting this communication. I consider this a matter that impinges on my professional reputation, and I reserve all rights in pursuit of a just resolution.

Sincerely,
Ronald Pies MD
Professor of Psychiatry

. . . . . . . . . . . . . . . .

MY RESPONSE

In his email, Dr. Pies raises two objections.  Firstly, he contends that the phrase “little white lie” as applied to the chemical imbalance theory was misattributed to him, on the grounds that the phrase had been used earlier by Robert Whitaker.  Secondly, he states that he has never accepted payment from pharmaceutical companies with the intent or purpose of promoting their products.

THE LITTLE WHITE LIE

On April 15, 2014, Dr. Pies published an article – Nuances, Narratives, and the ‘Chemical Imbalance’ Debate in Psychiatry – on Medscape.

The third paragraph of this article reads:

“Now, if you were to give credence to a recent online polemic posing as investigative journalism1, you would probably choose the first or second statement. In the narrative of the antipsychiatry movement, a monolithic entity called ‘Psychiatry’ has deliberately misled the public as to the causes of mental illness, by failing to debunk the chemical imbalance hypothesis. Indeed, this narrative insists that, by promoting this little white lie, psychiatry betrayed the public trust and made it seem as if psychiatrists had magic bullets for psychiatric disorders. (Lurking in the back-story, of course, is Big Pharma, said to be in cahoots with Psychiatry so as to sell more drugs).”

The “polemic posing as investigative journalism” (Ref #1) is an ungracious, and, in my view, unwarrantedly cynical, reference to Bruce Levine’s March 5 2014, interview with Robert Whitaker.  In that interview, Robert is quoted as saying:

“By doing so [promoting the chemical imbalance theory], psychiatry allowed a ‘little white lie’ to take hold in the public mind, which helped sell drugs and of course made it seem that psychiatry had magic bullets for psychiatric disorders. That is an astonishing betrayal of the trust that the public puts in a medical discipline; we don’t expect to be misled in such a basic way.”

It is obvious in this quote, and from the surrounding text, that Robert is using the term “little white lie” as an understatement.  This is clear from the next sentence:  “…an astonishing betrayal of the trust that the public puts in a medical discipline…”.  It is also noteworthy that the phrase is inside quotation marks, which are often used to negate the substance of the enclosed material.

But in Dr. Pies’ statement in the Medscape article, there is nothing to suggest that understatement was intended, and nothing to suggest that the sentiment entailed was anything other than Dr. Pies’ own position.

Specifically, he did not place the phrase inside quotation marks.  And more generally, characterizing the chemical imbalance theory as a “little white lie” is consistent with the psychiatry-exculpating tone of Dr. Pies’ piece.  It is also consistent with the tone of other articles that Dr. Pies has written.  For instance, in Doctor, Is My Mood Disorder Due to a Chemical Imbalance? (2011), Dr. Pies wrote:

“Many patients who suffer from severe depression or anxiety or psychosis tend to blame themselves for the problem. They have often been told by family members that they are “weak-willed” or “just making excuses” when they get sick, and that they would be fine if they just picked themselves up by those proverbial bootstraps. They are often made to feel guilty for using a medication to help with their mood swings or depressive bouts.…So, some doctors believe that they will help the patient feel less blameworthy by telling them, ‘you have a chemical imbalance causing your problem.'”

A little white lie is an inconsequential falsehood, told to avoid causing embarrassment or hurt.  And this is precisely how Dr. Pies is presenting the chemical imbalance hoax in the passage quoted above:  a benign falsehood that will “help the patient feel less blameworthy”.

So, those of us reading Dr. Pies’ “Nuances…” article had every reason to read his description of the chemical imbalance theory as a little white lie, as his own position, and absolutely no reason to infer anything to the contrary.

In addition to this, Dr. Pies himself seems knowledgeable of these matters, and skilled in navigating these kinds of linguistic intricacies.  For instance, in the “Nuances…” article, Dr. Pies states:

“In the narrative of the anti-psychiatry movement, a monolithic entity called ‘Psychiatry’ has deliberately misled the public as to the causes of mental illness, by failing to debunk the chemical imbalance hypothesis.”

Here, Dr. Pies has made it perfectly clear that the characterization of psychiatry as a “monolithic entity” is not his position, but rather that of the antipsychiatry movement.

But no such construction is attached to his use of the phrase “little white lie”.

For Dr. Pies to contend that Drs. Lacasse and Leo misattributed the phrase to him is inaccurate and unreasonable.  The notion that “careful scholars” would have searched through the comments string and found Dr. Pies’ clarification is not convincing.  If Dr. Pies was aware that there was a misleading phrase in the article, he should have corrected it, not relied on his readers to search through a comments string looking for a correction, of whose existence they had no inkling.  The responsibility for the miscommunication sits squarely on his own shoulders.

And there are indications that Dr. Pies clearly understands this.  The “Nuances…” article which appeared in Medscape on April 15 2014, had been published earlier, on March 11, 2014, in Psychiatric Times.  But a month later, on April 11, it was updated on that siteIn the later version, the phrase “little white lie” has been changed to “simplistic notion”.  My interpretation of this at the time was that Dr. Pies had recognized that his earlier statement had been woefully inaccurate, and frankly insulting to people who had been harmed by the falsehood in question, so he made the change.  For some reason, a similar change was not made in the Medscape article until about two weeks ago, when its wording was amended to “simplistic formulation”.  If Dr. Pies didn’t believe that he had misexpressed himself, why did he feel the need to make these amendments?

So, to summarize the “little white lie” issue:

  1. In the original Psychiatric Times and Medscape articles, Dr. Pies characterized the spurious chemical imbalance theory as “this little while lie”. There was nothing in the wording of this statement to suggest that this was anything other than his own position.
  1. At some point in the next few weeks, Dr. Pies realized that his statement was inaccurate, or that he had misexpressed himself, and made an appropriate correction in the Psychiatric Times article, but not in the Medscape piece.
  1. In October 2015, Drs. Lacasse and Leo, accurately and appropriately, attributed the “little white lie” phrase in the Medscape article to Dr. Pies.
  1. Sometime in the last two weeks, the Medscape article was amended to read “simplistic formulation”.
  1. On November 4, 2015, Dr. Pies unjustly accused Drs. Lacasse and Leo of misattributing the phrase to him.

 . . . . . . . . . . . . . . .

CONFLICTS OF INTEREST

Here’s the entire passage from the Behavior Therapist article:

“Thus, while we don’t know why Ronald Pies himself didn’t speak out on the chemical imbalance issue decades ago, readers should be aware of his past financial relationship with pharmaceutical companies. He sounds vaguely critical of the drug industry in his recent articles and never discloses any history of financial conflicts-of-interest. However, Pies has received funding from GlaxoSmithKline, Abbot Laboratories, and Jannsen Pharmaceuticals—the makers of Paxil, Wellbutrin, Lamictal, Depakote, and Risperdal (Chaudron & Pies, 2003; Pies & Rogers, 2005).  For years, Paxil and Wellbutrin were advertised as correcting a chemical imbalance in the brain. These three companies have recently been fined a combined $6.7 billion for illegal marketing of their products.Pies has also consulted for ApotheCom, a ‘Medical Communications Agency’ that ‘provides services to support the commercialization of new products…[including]….publications planning, [and] promotional communications…’ (Pharma Voice Marketplace, 2015). While useful context, this isn’t uncommon among academic psychiatrists, and some would say it was par for the course in the 2000s.  However, in a public forum, more transparency is preferable.  Pies blames the drug companies for running misleading advertisements about chemical imbalance, belatedly admits he should have said something sooner, but fails to mention that he was paid to help them promote their products at the time the advertisements were running.

It’s important to realize that organized psychiatry doesn’t always remain silent, such as when the interests of psychiatric prescribers and pharmaceutical companies converge. In the mid-2000s, press releases endorsed by some of the most prominent psychiatrists in the United States were issued objecting to the FDA black box warning on SSRIs (e.g., American College of Neuropsychopharmacology, 2006; Healy, 2012). The APA also issued a press release defending antidepressants (APA, 2004; Healy, 2006). This was at a time when the chemical imbalance metaphor was omnipresent in direct-to-consumer advertising.  While that was seen as a pressing issue to present to the public, misleading messages on chemical imbalance were not.”  (p 209)

Footnote 1 reads:

“We want to be clear that we are not accusing Ronald Pies of anything.  Conflicts-of-interest are routine in academic psychiatry and many of the major pharmaceutical companies have been fined in the recent past.  We do believe that readers deserve to know of his past financial relationships with the drug companies that promoted their products as correcting a chemical imbalance.  The details of these financial relationships are not publicly available.”

I think the above text is clear, and speaks for itself.  It is noteworthy that Drs. Lacasse and Leo take specific pains to protect Dr. Pies from any kind of unjust criticism (“…we are not accusing Ronald Pies of anything.”)  It is also noteworthy that in his email Dr. Pies does not deny that he has consulted for ApotheCom.  Nor does he deny that he received payment for such consultations.  Nor does he deny that ApotheCom’s business is providing “services to support the commercialization of new products”.  Nor does he deny that he received payments from the other drug companies named.  Nor does he deny that these other companies promoted the spurious chemical imbalance theory in their ads.

Dr. Pies simply asserts that he has never accepted payments from pharmaceutical companies with the intent or purpose of promoting their products, and that he has never had ongoing financial relationships with any pharmaceutical company.  This is an unusual rebuttal, in that Drs. Lacasse and Leo never accused him of either of these activities.  I’ll discuss this in more detail later.

In the interests of clarity, I should point out at this stage in the discussion that the terms “promote” and “promotion” are value-neutral, and subject to degrees.  A person may promote a good thing (e.g. world peace), or a bad thing (e.g. racial hatred), and may promote something minimally or avidly.  In addition, a person might promote something  for payment, or gratuitously.

So, if a psychiatrist were to mention to a colleague, in the course of a private conversation, that he finds such and such a drug helpful in alleviating such and such a problem, he has, in effect, promoted the drug in question.  And, he, presumably, would consider this promotion to be a good thing.  Similarly, if a pharmaceutical company launches a massive advertizing campaign on a particular drug, this would also be considered a promotion of the product in question, and, if it resulted in an increase in sales, would be considered a good thing by the company in question.

Similarly, if a psychiatrist writes and publishes an opinion piece in which a certain drug is mentioned favorably, this is a promotion.  In fact, even a relatively neutral mention of a drug by an eminent psychiatrist could be construed as a promotion, along the lines of incidental placement of commercial products in movies.

Dr. Pies also asserts that the “allegation by Lacasse and Leo was not based on any direct knowledge” of his professional or contractual arrangements dating back to 2003.  And he indicated no intentions to make any such information public.

Here, however, are some facts that are in the public domain, interspersed with my comments and reflections.

1.  In July 2002, Dr. Pies published The ‘softer’ end of the bipolar spectrum in the Journal of Psychiatric Practice. He acknowledges that the article is “supported by an unrestricted grant from GlaxoSmithKline.”  The article is a literature review/opinion piece.  Here’s the abstract:

“The prevalence and diversity of bipolar disorder may be under-appreciated. Recent data suggest that when clinicians look beyond strict DSM-IV criteria for bipolar disorder, we find that as many as 5%-7% of the general public may suffer from some form of ‘bipolar spectrum disorder.’ At the same time, the comorbidity between bipolar disorder and other psychiatric conditions may create understandable confusion in diagnosis and treatment. Recognition of bipolar depression and the ‘soft end’ of the bipolar spectrum demands not only the identification of the hallmarks of bipolarity, but a heightened awareness of the problems of missed diagnosis and inappropriate treatment. By attending to some key historical and clinical clues, the psychiatrist is more likely to detect bipolar spectrum disorder and provide appropriate treatment for it.” [Emphasis added]

And here’s a quote from the “Treatment Recommendations and Conclusions” section:

“In the mean time, recent evidence suggests that lithium is at least moderately effective in many depressed bipolar patients,41 and that the anticonvulsant lamotrigine may be a feasible alternative to antidepressants in some depressed bipolar patients.42” [Emphasis added]

Lamotrigine (Lamictal) is an anticonvulsant made by GlaxoSmithKline.

Reference 42, on which Dr. Pies’ recommendation is reliant, is Calabrese JR, Bowden, CL, et al. A double-blind, placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression, J Clin Psychiatry 1999.  This study was funded by Glaxo Wellcome, which in January 2000 merged with SmithKline Beecham to become GlaxoSmithKline.  Three of the authors, John Ascher, MD, Eileen Monaghan, and David Rudd, PharmD, were GW employees.  In addition, the authors thank Gary Evoniuk, PhD, and Elizabeth Field, PhD for “editorial assistance with the manuscript.”  Dr. Evoniuk was, and incidentally still is, an employee of GSK.  According to her bio, Dr. Field worked for GSK from 1989 to 2001, and with astonishing candor, describes her work there as follows:

“I managed an international department of 24 medical publication professionals who wrote/edited manuscripts for peer-reviewed journals describing the results of GSK-sponsored clinical trials in conjunction with the author/investigators. This group supported almost all products in development and marketed by GSK” [Emphasis added]

So it is clear that GSK had a very considerable input into the wording and presentation of the Dr. Calabrese et al article.  The conclusion of the study was:  “Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.”

So essentially what we’ve got here is:  Glaxo Wellcome funds, and is heavily involved in the production of, a 1999 study which finds in favor of its drug lamotrigine (Lamictal).  And in 2002, GSK contracts with Dr. Pies to write an article on the “bipolar spectrum”, in which Dr. Pies, largely on the basis of Drs. Calabrese’s and Bowden’s findings, recommends the drug, albeit with a measure of caution, for “some depressed bipolar patients”.

But the plot thickens, for this is the same Dr. Calabrese who was described in United States vs. GSK (2012) as “…GSK’s greatest proponent for the use of Lamictal in the treatment of bipolar disorder…”  Dr. Bowden is also mentioned frequently in the same lawsuit.

To provide context for this discussion, I have attached to this post  – as Appendix A – a copy of the Lamictal section of the GSK lawsuit.  It’s a sordid tale, which describes in close detail how GSK illegally and vigorously promoted Lamictal as a “treatment for bipolar disorder”.  The outcome of this lawsuit was that GSK was fined $3 billion, the largest fine for activity of its sort in American history.

I need to emphasize that my introduction of the GSK lawsuit material is to provide context.  Dr. Pies is not named in the complaint, and there is no suggestion from any source that he was complicit in GSK’s illegal activities.  Nor am I suggesting that Dr. Pies was complicit in the activities of Drs. Calabrese and Bowden.  But Dr. Pies did lend credence to their work, by quoting them, and by relying on their findings, even though the extensive GSK involvement in the creation of their report was, and still is, public information.

There are two paragraphs in the United States vs. GSK complaint that have particular relevance.

“471. Just as troublesome as the Lit Alerts and Faxbacks, were the numerous studies by Calabrese, distributed by GSK, which suggest the efficacy and use of Lamictal in patients with bipolar II.”  [Emphasis added]

In other words, the distribution of the Calabrese studies was an integral part of the illegal promotion of Lamictal for bipolar disorder.  And Dr. Pies, by publicizing, and lending credence to, these studies, became a significant, though unwitting, link in this distribution chain.

Paragraph 474 is also important.

“474. GSK’s extremely aggressive off-label campaign for Lamictal included spending large sums of money in the form of unrestricted grants, membership on advisory boards and speaker’s fees on physicians and researchers who served as ‘national thought leaders.’ As with campaigns for other drugs, the campaign for the use of the drug Lamictal in the treatment of bipolar disorders began with the widespread promotion of ‘disease awareness.'”  [Emphasis added]

In other words, GSK’s awarding of unrestricted grants was also an integral part of their promotional campaign, and as we shall see below, Dr. Pies was the recipient of several unrestricted grants from GSK.  Additionally, Dr. Pies’ opening statement in the “Softer End” article that “… 5%–7% of the general public may suffer from some form of ‘bipolar spectrum disorder.'” sounds very like the “widespread promotion of ‘disease awareness'” mentioned in paragraph 474 above.

Given the extent and vigor of GSK’s illegal promotional campaign, it was perhaps almost inevitable that a person of Dr. Pies’ academic stature and unimpeachable reputation for personal integrity, would become a “target” for GSK’s talent scouts.

In 2008, Nassir Ghaemi, MD, et al published an article Publication Bias and the Pharmaceutical Industry: The Case of Lamotrigine in Bipolar Disorder in Medscape.  The article takes to task the drug industry generally (and GSK in particular) for not publishing, and perhaps even concealing, research studies that show their products in a negative light.  Dr. Ghaemi et al focus specifically on “studies with lamotrigine in bipolar disorder”.  Here’s a quote from their abstract:

“In this paper, we review the case of studies with lamotrigine in bipolar disorder, describing evidence of lack of efficacy in multiple mood states outside of the primary area of efficacy (prophylaxis of mood episodes). In particular, the drug has very limited, if any, efficacy in acute bipolar depression and rapid-cycling bipolar disorder, areas in which practicing clinicians, as well as some academic leaders, have supported its use.” [Emphasis added]

Obviously I don’t know if Dr. Ghaemi et al  had Dr. Pies in mind when they were writing this, but as quoted earlier, Dr. Pies had written in 2002 that “recent evidence suggests that…lamotrigine may be a feasible alternative to antidepressants in some depressed bipolar patients.”

. . . . . . . . . . . . . . . .

In passing, I should probably comment on the term “unrestricted grant”.  Strictly speaking, this means that the money is given with no strings attached.  The grantee is assured the freedom to express and publish his views with no pressure from the grantor.  In practice, there often are pressures, subtle and otherwise.  Here’s what the distinguished Professor Emeritus of Medicine at UCLA, Jerome Hoffman, MD, wrote on this matter on June 12, 2013, in a guest post on the blog site Common Sense Family Doctor:

“Excuse me, but Pharma doesn’t throw away its money. There is no such thing as an unrestricted grant; if it didn’t buy value in return, why would they pay for it? And if the author didn’t write something they like to read, do you think he’d ever get another unrestricted grant?”

And here’s what the highly-respected psychiatrist Daniel Carlat, MD, wrote on June 17, 2007:

“While the term ‘unrestricted’ implies that the company had no strings attached to its money, the reality is that any physician or MECC (medical education communication company) who receives drug company funding knows that their lecture or article will be closely perused by those with the cash, and that future ‘gigs’ will be dependent on whether the company feels their product is shown in a favorable light.”

As we will see later, Dr. Pies has received several unrestricted grants from GSK.

. . . . . . . . . . . . . . . .

2.  In December 2002, Dr. Pies wrote an opinion piece: Combining lithium and anticonvulsants in bipolar disorder: a review, for the Annals of Clinical Psychiatry.  The article was funded  ” by an unrestricted grant from GlaxoSmithKline.”  Here’s a quote from the abstract:

“More recent reports suggest that lithium may be safely and effectively combined with lamotrigine, and perhaps with topiramate, although controlled studies are required.” [Emphasis added]

Here are some quotes from the body of the article:

” Since 1994, there have been at least 21 open-label, uncontrolled case reports or studies examining lamotrigine in bipolar disorder, with a cumulative control group of over 300 patients (26,27). While a review of this literature is beyond the scope of the present paper, a few points are worth noting. In their own review of 14 open clinical reports involving 207 patients with bipolar disorder (66 with rapid cycling), Calabrese et al. (26) concluded that lamotrigine demonstrated moderate-to-marked efficacy in depression, hypomania, and mixed states; however, efficacy in hospitalized manic patients was not clearly shown, and many of these studies used lamotrigine as add-on (adjunctive) therapy. In the Bowden et al. study (27), lamotrigine was evaluated in patients with refractory bipolar disorder, either as monotherapy (n = 15) or as add-on therapy (n = 60). A total of 23 subjects (31 %) were taking lithium at the initiation of the study; three additional patients received lithium later in the study. Overall, both rapid-cycling and nonrapid-cycling patients experienced symptom reduction and functional improvement over the course of 48 weeks.” [Emphasis added]

Reference 27 is a Glaxo Wellcome-funded study by Drs. Bowden, Calabrese, et al.  Four of the authors were GW employees.

Here are some more quotes from Dr. Pies’ article:

“The patient populations in open studies of lamotrigine have been quite heterogeneous, and lamotrigine has been used as both add-on and monotherapy.  These studies have suggested lamotrigine’s efficacy in depressed, hypomanic, and mixed bipolar patients.” [Emphasis added]

Lamotrigine monotherapy is generally well tolerated.” [Emphasis added]

“From the standpoint of pharmacokinetic interactions, the combination of lamotrigine and lithium appears to pose no significant problems. Specifically, administering lamotrigine with lithium does not significantly alter the pharmacokinetics of lithium (35). Preliminary indications indicate that the combination of lamotrigine and lithium is well tolerated in most patients.” [Emphasis added]

“The addition of lamotrigine to lithium seems most useful for patients refractory to lithium alone who show prominent depressive symptoms and/or rapid cycling.”

But a product can also be promoted by criticizing the competition, in this case, divalproex, (Depakote):

“A larger cohort study of lithium-divalproex [Depakote]combination has yielded mixed results. Specifically, in an open study, Calabrese et al(19) examined large cohorts of rapid-cycling bipolar patients ( N = 271), over a 6-month study period. Of the total group, 215 had comorbid alcohol or drug abuse, 56 did not. In the group as a whole, the combination of lithium and divalproex was associated with marked acute and continued antimanic efficacy in 85% of patients and marked antidepressant efficacy in 60%. However, only one half of patients experienced bimodal mood stabilization.  Premature discontinuation of treatment was disproportionately associated with refractory depression compared with refractory hypomania/mania/mixed states ( n = 41 vs 14). Comorbid alcohol/substance abuse did not directly affect response rates in compliant patients, but did worsen prognosis by increasing rates of poor compliance. The majority of patients receiving lithium/divalproex therapy who required additional treatment were depressed. Indeed, at the time of presentation, most patients with rapid-cycling bipolar disorder are in the depressed phase of illness, which appears to be the “hallmark” of rapid cycling (19).  Given this observation, and that antidepressant use has been discouraged in rapid cyclers, the authors note the pressing need for a pharmacotherapy that markedly reduces depressive symptoms without provoking ‘switching’ or cycle acceleration.” [Emphasis added]

Here again, note that reference 19 which Dr. Pies is citing is a study conducted by Dr. Calabrese, Bowden, et al in 2001, and was funded by Glaxo Wellcome and NIMH.

. . . . . . . . . . . . . . . .

3.  In October 2002, Dr. Pies published Have we undersold lithium for bipolar disorder? as an editorial in the Journal of Clinical Psychopharmacology. The editorial was funded by an unrestricted grant from GSK.  Here’s a quote from the conclusion:

Lamotrigine looks very promising for bipolar depression and prophylaxis, but more studies are needed to define and solidify its role. The same goes for topiramate. Olanzapine, while useful in mania and perhaps as an adjunctive agent in bipolar depression, has yet to prove itself as monotherapy in bipolar prophylaxis. Furthermore, concerns about the neuroendocrine effects of valproate and olanzapine—both of which have FDA labeling in bipolar disorder—must also give us pause. As for gabapentin, there are still no randomized, controlled studies of monotherapy showing this agent to be effective in any type or phase of bipolar disorder.”  [Emphasis added]

Here’s another quote from the body of the editorial:

“Recently, Calbrese et al.13 presented data from two large, double-blind, placebo-controlled, studies comparing lamotrigine and lithium in the maintenance treatment of bipolar I disorder. While both active agents delayed time to ‘any’ bipolar event, a separate analysis (manic/hypomanic/mixed vs. depressive events) found that lamotrigine had more robust effects than lithium in delaying onset of depressive episodes.” [Emphasis added]

Reference 13 is to: Calabrese JR, Bowden CL, et al. Lamotrigine or lithium in the maintenance treatment of bipolar I disorder [abstract NR 236]. Presented at the American Psychiatric Association Annual Meeting, Philadelphia, PA, 2002.

. . . . . . . . . . . . . . . .

4.  In February 2006, Dr. Pies and Patricia Marken, PharmD, co-authored an opinion piece Emerging Treatments for Bipolar Disorder: Safety and Adverse Effect Profiles in the Annals of Pharmacotherapy. The article was “supported by an unrestricted grant from GlaxoSmithKline.”  Here are the authors’ conclusions:

“Pending the results of ongoing controlled studies, several emerging agents may be useful additions to the therapeutic arsenal for BPD.” [bipolar disorder]

And here are some quotes from the body of the paper:

Lamotrigine [Lamictal] is the only newer AED [anti-epileptic drug] with randomized, placebo-controlled data supporting its use as maintenance treatment in BPD.” [Emphasis added]

Lamotrigine is the most studied of all emerging treatments for bipolar maintenance.72 It appears to be more useful in bipolar depression than in mania.72” [Emphasis added]

Lamotrigine was well tolerated, with an adverse event profile similar to that of placebo. Lamotrigine did not appear to induce mania and was not associated with sexual adverse effects,79 weight gain,80 or withdrawal symptoms.79” [Emphasis added]

Reference 72 is to a study by Drs. Bowden, Calabrese et al, 2003.  It was funded by GSK.  Four of the authors were GSK employees, and a further five GSK employees are acknowledged for assistance “in the preparation of this article.”

Reference 79 is to Bowden et al, 2004.  Three of the six authors were GSK employees.

And at the end of the Drs. Pies and Marken article (before the references) it states:  “We gratefully acknowledge Drs. Jacqui Brooks MBBCh MRC Psych and Laurie Barclay MD for their contributions during the preparation of this manuscript.”  No information is provided as to Dr. Brooks’ or Dr. Barclay’s affiliations, or who was paying for their contribution.  But Dr. Brooks’ bio is online, and according to this, she is currently Senior Vice President Medical Strategy at RMEI [Robert Michael Educational Institute].

Dr. Brooks’ bio also states:

“Seasoned healthcare executive with strong blend of clinical (trained psychiatrist) and strategic leadership accomplishments. Documented capacity to analyze evolving environments, provide strategic direction, and successfully lead teams in developing innovative, high-quality products and brand strategies. Proven success in business growth and development in the medical communications environment.” [Emphasis added]

There is no indication in Dr. Brooks’ bio that she ever worked as a psychiatrist.  Her employment history shows that from 2002 to 2005, she was working for ApotheCom Associates as VP Scientific Affairs, Senior Medical Director.  ApotheCom describes itself as “…a Global Medical Communications Powerhouse…”  PharmaVoice provides the following description:

“ApotheCom provides services to support the commercialization of new products at a global level as well as promotional programs for the US market. Services include thought-leader optimization, publications planning, promotional communications and education programming.”

Drs. Pies’ and Marken’s “Emerging Treatments…” article was published on January 10, 2006, so was probably developed during 2005, and it seems likely that Dr. Brooks’ contribution to the manuscript was in her capacity as an ApotheCom employee.  I have no way of knowing who was paying for ApotheCom’s services with regards to this paper, but it is in the public domain that in 2002, GSK made an educational grant to ApotheCom Associates for an article by Robert Hirschfield, MD.

Nor have I any information as to what kind of contribution Dr. Brooks might have made to the manuscript in question.  But her career and bio summary suggest that it might have been more in the area of “brand strategies” and “business growth” than psychiatric technicalities.  Why would an experienced and eminent psychiatrist-writer, like Dr. Pies, need help with a manuscript on the treatment of bipolar disorder from a “seasoned healthcare executive”, employed by a company that specializes in thought-leader optimization, publications planning, promotional communications and educational programming?  It is, I think, particularly noteworthy, that in the acknowledgement of Dr. Brooks’ contribution to “the preparation of the manuscript”, no information is provided concerning her affiliations, or who was paying for her services.  This, I suggest, constitutes, at a minimum, incomplete disclosure.

I was unable to find any information on Laurie Barclay, MD.

. . . . . . . . . . . . . . . .

5.  In August 2006, Dr. Pies and D.F. MacKinnon, MD, published: Affective instability as rapid cycling: theoretical and clinical implications for borderline personality and bipolar spectrum disorders in the journal Bipolar Disorders.  The article, which is a literature review/opinion piece, was “Supported by an unrestricted grant from GlaxoSmithKline.”

Here are the article’s conclusions:

“The same mechanism may drive both the rapid mood switching in some forms of bipolar disorder and the affective instability of borderline personality disorder and may even be rooted in the same genetic etiology. While continued clinical investigation of the use of anticonvulsants in borderline personality disorder is needed, anticonvulsants may be useful in the treatment of this condition, combined with appropriate psychotherapy.” [Emphasis added]

Note that lamotrigine (Lamictal) is an anticonvulsant.

And here are some interesting quotes from the article:

“To our knowledge, there are only two randomized,  double-blind, placebo-controlled studies of anticonvulsants in well-defined rapid cycling populations, both by the same group, and only one currently in the literature (59). In the published study, 182 rapid cycling patients were randomized to lamotrigine monotherapy or placebo. The study found that 41% of lamotrigine-treated versus 26% of placebo-treated patients were stable without relapse during 6 months of monotherapy. Patients with rapid cycling bipolar II disorder consistently experienced more improvement than did bipolar I patients. Most patients who were assigned to double-blind treatment were in the midst of a depressive episode, suggesting antidepressant effects of lamotrigine in bipolar disorder, consistent with the results of a separate, open-label trial of lamotrigine versus lithium in rapid cycling patients (60).” [Emphasis added]

Reference 59 is to a 2000 Calabrese, JR, Bowden, CL et al study funded by Glaxo Wellcome.  Four of the authors were GW employees, and the authors acknowledge assistance from Gary Evoniuk, PhD and Tracey Fine, MSc “in the preparation” of the article.  Both Dr. Evoniuk and Ms. Fine were GW employees at the time this study was conducted.  Ms. Fine’s position was Medical Publications Specialist.

Here’s another quote from Drs. Pies’ and MacKinnon’s opinion piece:

“Preliminary data suggest that lamotrigine may also have benefits in borderline personality disorder, with or without comorbid bipolar disorder.  In an open case series of eight medication-refractory borderline personality disorder patients without concurrent major mood disorders, lamotrigine produced sustained remission in half of those who completed the trial, with notable benefit against impulsive sexual, drug-taking, and suicidal behaviors.(69)” [Emphasis added]

Reference 69 is to: Pinto OC and Akiskal HS, 1998 which was funded by Glaxo Wellcome.

Here are more quotes from the Drs. Pies and MacKinnon opinion piece:

“Randomized, double-blind, controlled studies using lamotrigine appear warranted in this population; however, until these are completed, the utility of lamotrigine in borderline patients remains uncertain.  Nevertheless, one can conclude from the juxta-position of these studies of anticonvulsants in rapid cycling bipolar disorder and borderline personality disorder that at least some anticonvulsants are effective in alleviating not only the affective instability common to both conditions, but also specific measures of what have heretofore been considered fixed traits among borderline patients.” [Emphasis added]

Note how the initial note of skepticism pending the completion of randomized controlled trials is effectively neutralized by the material after the words:  “Nevertheless one can conclude…”.  And note the strength of the assertion:  One can conclude that some anticonvulsants (e.g. Lamictal?) can remediate what have previously been considered fixed traits!

“Once the biological roots of mood instability are better understood, there may be much more to contribute to the understanding of the development of our conventional notions of character and personality.”

And, presumably, more perceived justification for the use of psychiatric drugs to “fix” problems of personality and character.

“We conclude that in at least a sub-group of cases, borderline personality disorder may be an atypical presentation of a primary mood disturbance, probably related to the broad spectrum of bipolar-like disorders. It is premature to recommend anticonvulsants in the routine treatment of patients with borderline personality disorder; however, it seems that anticonvulsants may belong in the psychiatrist’s armamentarium for treatment of this condition.”

Here again, note how the appropriate cautionary lead-in is neutralized by the statement after the word “however”.  The suggestion that anticonvulsants belong in a psychiatrist’s “armamentarium” clearly entails the notion that these products should be used in the “treatment” of “borderline personality disorder”.

And as mentioned before, a drug can be promoted by knocking the opposition, in this case divalproex (Depakote).

“The second randomized, double-blind, controlled study (61) involved a 20-month, parallel group comparison of 60 patients with a history of recent rapid cycling bipolar I or II disorder.  Patients were randomized to lithium or divalproex monotherapy in a balanced design after stratification for bipolar type I and II. For subjects on either lithium or divalproex, about half suffered a relapse: a third into depression, and one-fifth into mania or hypomania. Although clearly better than placebo, it appears there was no benefit of divalproex versus lithium.”

Reference 61 is to a study by Dr. Calabrese, et al.  The study was funded by the NIMH and the Stanley Medical Research Institute.

. . . . . . . . . . . . . . . . .

DISCUSSION

I don’t think there can be any doubt, that in the five papers discussed above, Dr. Pies and his various co-authors did make numerous favorable mentions of the drug lamotrigine, and that the articles were funded by grants from GSK.

Dr. Pies could, of course, respond to all this by stating that he helped promote Lamictal on its merits alone, and that this promotion had nothing to do with the funding and/or manuscript assistance that he coincidentally received from the manufacturer of this product (GlaxoSmithKline).  And he could contend that he cited the studies by Drs. Calabrese and Bowden purely on their merits.  And all of this could well be true.

But as Dr. Pies himself wrote in a Psychiatric Times article – The Age of Conflicts—of Interest – on August 1, 2008:

“…the physician or researcher may not even be aware of his real motivation. We are all quite capable of rationalizing our own self-interest in the name of the patient’s well-being,’  ‘the need for the latest technology,’ and so on.”

Dr. Pies could also argue that in the above examples, I have cherry-picked the quotes, and that his treatment of these topics is more balanced than I have portrayed.  And indeed, there would be an inevitable measure of truth to this contention.  Obviously I can’t quote the articles in their entirety, and  Dr. Pies does sometimes mention drawbacks in the sponsor’s drug, and positive aspects of a competitor’s product.  But I have tried to be fair, by selecting quotes that convey the general tone of each piece with regards to lamotrigine, and, I encourage readers to consult the articles in question, and decide this matter for themselves.

Dr. Pies could certainly quibble over any particular quote – or even over any particular paper – as to whether it constitutes promotion of a pharma product.  But of greater importance is the cumulative effect of the multiple passages quoted above in the context provided by the GSK lawsuit complaint and the multiple GSK-sponsored studies.  In this post I have discussed and quoted from five opinion pieces, authored or co-authored by Dr. Pies.  All of the articles were funded by GSK, and all refer to studies conducted by Dr. Calabrese et al.  And remember, Dr. Calabrese is described in the GSK lawsuit as “…GSK’s greatest proponent for the use of Lamictal in the treatment of bipolar disorder…”

In my view, Dr. Pies’ statements in the various articles would appear, to an impartial reader, as recommendations or promotions of lamotrigine.  And it is worth pointing out that I am neither particularly skilled, nor particularly systematic, in conducting literature searches.  It is entirely possible that a more competent searcher would uncover a great deal more material of a comparable nature.  And it also needs to be borne in mind that I have focused on only one drug – Lamictal.  A search of Dr. Pies’ writings concerning other pharma products could conceivably reveal similar complications.  I did, for instance, come across a 2005 article written by Dr. Pies and Winkelman which stressed the efficacy of the sleeping pill eszopiclone (Lunesta), manufactured by Sepracor, now Sunovion.

This reported efficacy was based on Ref # 146, a 2003 study by Andrew Krystal, MD et al.  The Krystal et al study concluded:

“Throughout 6 months, eszopiclone improved all of the components of insomnia as defined by DSM-IV, including patient ratings of daytime function. This placebo-controlled study of eszopiclone provides compelling evidence that long-term pharmacologic treatment of insomnia is efficacious.”

There were seven authors of this study.  Three of the authors are listed as “consultants, investigators and advisory board members to Sepracor.”  A fourth author is listed as a Sepracor consultant.  And the remaining three authors were Sepracor employees.

In their opinion piece, Drs. Pies and Winkelman did not point out that the Krystal et al study was largely a Sepracor in-house project.  Nor did they disclose the funding source (if any) for their opinion piece, but in their acknowledgement section, they wrote:

“The authors would like to acknowledge Sepracor Inc. for its assistance in the preparation of this manuscript.”

I have no way of knowing what this assistance entailed, but it does imply that Sepracor did – at the very least – have some collaborative input in the wording of the article.  It seems unlikely that any such input would work to the detriment of their product.  Why would an eminent psychiatrist of Dr. Pies’ stature need help from a pharmaceutical company to write an opinion piece on the treatment of insomnia?  What kind of help did Sepracor provide?

. . . . . . . . . . . . . . . .

It also needs to be stressed that, as far as I know, Dr. Pies has done nothing wrong, in any formal sense of the term.  He has accepted grant money from pharmaceutical companies to write opinion pieces on various psychiatric topics, and if he came down in favor of the grantor’s product, there are no definite indications that his motivations were anything but pure.  It also needs to be stated that Dr. Pies is a prolific writer, and that the articles cited above represent only a tiny fraction of his published work.  It is possible that a more comprehensive review of his writing over the period in question would show that these kind of industry-sponsored opinion pieces constituted a small fraction of his overall output.

A further question in all of this is why Dr. Pies should be so upset at the suggestion that he had received payment to write articles that helped promote psychiatric drugs.  If Dr. Pies believes that the drugs are efficacious and generally benign, why shouldn’t he help promote them, and why shouldn’t he be afforded reasonable compensation for this activity, particularly when he discloses these arrangements in the papers.  Why should the acceptance of payments in these matters have any bearing on his professional reputation?

But over-riding all of this, is the obvious fact that Dr. Pies has mis-read the phrase  “…he was paid to help promote their products…”  Specifically, he has apparently formed the belief that the phrase purports to describe his motivation in these transactions.  In fact, the use of the passive voice (he was paid) makes it clear that it is the payer’s motivation that is the matter of focus, not the payee’s.

To clarify the distinction, compare the two statements:

He was paid to help promote the drugs.

And

He accepted payment to help promote the drugs.

The first statement clearly entails the notion that the payers were paying the individual with the intention – and presumably expectation – that he would help promote the drugs.  The statement tells us nothing about the payee’s intentions, or even his awareness, of the payer’s intentions.  The second statement, by contrast, clearly purports to describe the payee’s motivation, but Drs. Lacasse and Leo made no statement of that kind.

There is a perfect parallel to this in the drug industry’s widespread use of “thought leaders” to promote their products.  This particular hoax was thoroughly explained by Daniel Carlat, MD, in his 2010 book “Unhinged”.  Here’s how it worked:

A drug rep would approach a psychiatrist and tell him that he – the psychiatrist – was considered a “thought leader” or “key opinion leader” in the area, and that they would like to recruit him to give lectures and presentations to other psychiatrists on the value of a particular drug.  The drug company would train the psychiatrist, and would provide slides and other teaching aids, and would pay the psychiatrist for delivering the presentation.

And this is where it gets subtle.  The psychiatrist thought that the targets of these endeavors were the psychiatrists in the audience – that he was being paid to promote the drug in question to them.  In reality, and this was what Dr. Carlat exposed, the lecturer-psychiatrist himself was the actual target.  By getting him to extol the merits of a drug to his peers, the drug company was actually generating pressure within the lecturer to prescribe the drug more frequently himself.  And the tactic was extremely successful!

So, from the psychiatrist’s point of view, the following statement would be true:

I was paid to give lectures on this drug.

But from the drug company’s point of view, the following statement was true.

We paid him so that he would prescribe this drug more often.

Obviously the psychiatrist in question would object to the latter statement, because he had no knowledge of the drug company’s motivation or tactics.

Similarly, with regards to GSK’s “unrestricted grants, there can be no doubt, given the context outlined above, that GSK was awarding these grants to help promote Lamictal.  And this is the case, even though from Dr. Pies’ point of view, he was merely accepting payment from GSK to write scholarly articles.

In short, like the psychiatrists in Dr. Carlat’s account, he was systematically misled as to the real purpose of the articles.

. . . . . . . . . . . . . . . .

It is worth remembering that this matter began with Dr. Pies’ efforts to distance psychiatry from the chemical imbalance theory of depression, and to lay the blame, or at least some of the blame, for this hoax, onto pharma commercials.

The central point of this entire issue is that at the time these deceptive commercials were running, and running very successfully, Dr. Pies was contracting with these same companies to write articles about their products, and his payments came, at least in part, from revenues generated by these very ads.  Dr. Pies’ current condemnations of pharma’s past excesses would be more convincing today if he had lodged clear statements of protest at the time, or better still, if he had refused to accept their grant contracts, on the basis that the money was tainted.

FINALLY

One of my main purposes in writing this website is to draw attention to psychiatry’s spurious foundations, and to its inherently destructive and disempowering “treatments”.  I also critique the work of writers who seek to promote or exculpate psychiatry, including Dr. Pies.

But my critiques are always directed towards the issues, and are always directed at errors of fact or logic.  In particular, I take special pains to avoid anything that could, even remotely, be construed as a personal attack, or an attack on an individual’s character.  In the case of Dr. Pies, I have always afforded him the respect due to a person of his stature, and have frequently expressed the belief that his primary error is one of loyalty:  that he loves his chosen profession, in the word’s of Shakespeare’s Othello, “not wisely but too well”.

I have read and re-read Dr. Pies email, and in the light of that communication, I have re-read my earlier post.  But I can find nothing in that post that could reasonably be considered false, malicious, or defamatory.

But I’m also a realist, and I recognize the obvious fact that we are all capable of being biased in respect of our own writings.  I am open to suggestions concerning this matter, and if Dr. Pies were to specify which statement or statements on my part have generated a sense of grievance on his, I would be happy to take another look at the document.  And if, in the light of such re-examination, Dr. Pies’ expressions of concern are credibly vindicated, then I will apologize publicly, and retract the statement(s) in question.

. . . . . . . . . . . . . . . .

Appendix A:  Section IX of United States of America vs. GlaxoSmithKline, PLC

  1. GSK’S OFF-LABEL MARKETING OF LAMICTAL
  1. In December 1994, Lamictal (active ingredient lamotrigine) was FDA approved for use as adjunctive therapy in adults with partial seizures, and as adjunctive therapy in the generalized seizures of Lennox-Gastaut syndrome in adults and pediatric patients ages two and older.
  1. However, despite the narrow indications for which it was approved, GSK heavily marketed Lamictal for the treatment of bipolar disorders both before and during the period it was pending a supplemental new drug application for treatment of bipolar I disorder, which was finally granted by the FDA on June 20, 2003.
  1. Off-Label Promotion to Bipolar Patients
  1. GSK’s aggressive marketing of Lamictal prior to its approval for use in the treatment of bipolar I disorder proved extremely lucrative. Lamictal grew by 33% in the year 2000 (with total U.S. sales of $210 million) and continued to grow in the following years. In a press announcement for year 2003 GSK boasted that Lamictal was approaching ‘blockbuster status’ with sales that grew by 31% to approximately $1 billion.
  1. Curiously, there is no data that would support a commensurate rise in partial seizures in adults or Lennox-Gastaut Syndrome, the only approved indications for Lamictal prior to June of 2003.
  1. Ultimately, the aggressive and illegal pre-approval marketing served the dual purpose of reaping significant gains prior to approval for treatment of bipolar I disorder as well as assuring GSK of a nationwide network of health care providers ready to prescribe the drug for bipolar disorders the minute it received FDA approval.
  1. Over the course of nearly ten years of off-label marketing of Lamictal, billions of dollars in sales were generated prior to the 2003 indication for bipolar I, as alleged infra.
  1. Accordingly, GSK, in promoting Lamictal by willfully misrepresenting the FDA approved uses, engaged in egregious and knowing off-label marketing.
  1. Off Label Promotion for all Bipolar Disorders
  1. Despite the fact that Lamictal was only FDA approved for treatment of partial onset seizures in 1994, since its launch, sales representatives were trained to promote the drug as an effective treatment for all bipolar disorders.
  1. Although there are several types of bi-polar disorders, as alleged infra, bipolar I is the most severe and the most rare. Notably, the drug was never approved by the FDA for bipolar II disorder or any of the four (4) other variations on bipolar disorder listed below.
  • Bipolar I disorder involves episodes of severe mood swings, from mania to depression.
  • Bipolar II disorder is a milder form, involving milder episodes of hypomania that alternate with depression. Bipolar II is a more broadly defined mental illness and encompasses more patients.
  • Cyclothymic disorder describes even milder mood changes.
  • With mixed bipolar disorder, there is both mania and depression at the same time, resulting in a person having feelings of grandiosity and racing thoughts, often resulting in an irritable, angry and moody feeling.
  • Rapid-cycling bipolar disorder is characterized by four or more mood episodes that occur within a 12-month period. Some people experience multiple episodes within a single week, or even within a single day. Rapid cycling tends to develop later in the course of illness. Women are more likely than men to have rapid cycling. A rapid-cycling pattern increases risk for severe depression and suicide attempts.
  1. Despite the lack of any bipolar related indication until 2003, sales representatives were provided with materials designed to promote the drug for global bipolar disorders. Even after it received approval for bipolar I disorder in 2003, sales representatives were trained not to call attention to the distinctions among the various types of bipolar disorder unless a physician inquired.
  1. As evidence of the pre-indication marketing and training, one need look no further than the 2001 GSK Selling Resource Guide for Lamictal. The Resource Guide provides scripts for sales reps to address requests for information on Lamictal and bipolar depression suggesting that there were numerous inquiries into this usage. 7AC 0000413-0000430.
  1. In furtherance of their bipolar marketing efforts, GSK engaged in an aggressive campaign aimed at pushing sales representatives to use the FaxBack program discussed in the Resource Guide as a marketing tool.
  1. Specifically, in the aforementioned 2001 Resource Guide, sales representatives were instructed to direct the physicians to “Faxback Number 5” for information regarding the use of Lamictal and bipolar disorder. This faxback incorporated the findings of Dr. Joseph R. Calabrese, and others, which positively detailed the use of Lamictal in patients suffering from bipolar I and II, mania, unipolar depression, and as a monotherapy. 7AC 0000419
  1. Most troublesome is the fact that GSK was aware of its illegal strategic use of the FaxBack program, yet made a conscious and deliberate effort to cover up its actions.
  1. For example, at a management training program in July 2002, Relator Hamrick was instructed by a manager-in-training that, with respect to the detailing of Lamictal for bipolar to psychiatrists, the record of every contact report should automatically include the phrase ‘Dr. inquired about bipolar disorder” thereby effectively circumventing the requirements of the FDCA with regards to disseminating literature concerning non-approved uses.
  1. In addition to the FaxBacks, GSK frequently distributed “Lit Alerts” to its sales force allegedly for the purpose of educating the drug reps. The Alerts, essentially a cliff-note version of a drug specific study, were routinely carried by sales representatives to aid in answering any questions posed by physicians. The fact that the Lit Alerts were, by their very nature, off label marketing tools, makes their distribution by GSK even more egregious.
  1. Specifically, in August 2002, a Lit Alert was distributed to Lamictal sales representatives discussing the use of Lamotrigine as an augmentation agent in treatment resistant depression (‘TRD’), a use for which it has never received approval. 7AC 0000431-0000433.
  1. Subsequent to the TRD Lit Alert, in April 2003 GSK distributed another study titled ‘Lamictal as Maintenance Treatment in Recently Manic or Hypomanic Bipolar I Patients.’ This Lit Alert served only to fan the flames of an already rampant bipolar campaign and was referenced widely in sales calls. 7AC 0000434-0000438.
  1. Just as troublesome as the Lit Alerts and Faxbacks, were the numerous studies by Calabrese, distributed by GSK, which suggest the efficacy and use of Lamictal in patients with bipolar II.
  1. Although Lamictal never received an indication for bipolar II disorder, GSK maintained its effective off label campaign and continued to forge strong relationships with its prescribing physicians ultimately pushing the boundaries by suggesting Lamictal’s effectiveness as a treatment option for bipolar II disorder.
  1. In fact, since the dosage of Lamictal must be increased slowly from a subtherapeutic level to a therapeutic level, acute mania and Bipolar II never received an indication.

“2. GSK’s Improper Use of National Thought Leaders to Promote the Off-Label Marketing of Lamictal

  1. GSK’s extremely aggressive off-label campaign for Lamictal included spending large sums of money in the form of unrestricted grants, membership on advisory boards and speaker’s fees on physicians and researchers who served as ‘national thought leaders.’ As with campaigns for other drugs, the campaign for the use of the drug Lamictal in the treatment of bipolar disorders began with the widespread promotion of “disease awareness.”
  1. Key figures in GSK’s national promotion of Lamictal for treatment of bipolar disorders prior to its indication were Dr. Joseph R. Calabrese of Cleveland, Ohio and Dr. Charles L. Bowden of San Antonio, Texas.
  1. As previously discussed, Dr. Calabrese, in particular, was GSK’s greatest proponent for the use of Lamictal in the treatment of bipolar disorders and published articles advocating the use of Lamictal in bipolar disorder as early as 1998. Dr. Calabrese has widely published his opinion that there is need for a greater awareness of the prevalence of bipolar disorders in the United States, stating that the disease impacts as many as 4% of the total population (11,000,000 people) yet is ‘largely undiagnosed.’
  1. In his promotion of the use of Lamictal for bipolar disorder, Dr. Calabrese wrote about a new nomenclature (‘above the line/below the line’) advocating that Lamictal was clearly superior to other commonly prescribed medications such as Lithium. Dr. Calabrese also defended the drug from the accusation that the risk of serious side-effects, such as Stevens- Johnson Syndrome4, outweighed the benefits of prescribing the medication.

4 Stevens-Johnson syndrome is a rare, serious disorder in which the skin and mucous membranes react severely to a medication, in this case, Lamictal, or infection. Often, Stevens-Johnson syndrome begins with flu-like symptoms, followed by a painful red or purplish rash that spreads and blisters, eventually causing the top layer of your skin to die and shed.  4612704 117

  1. In addition to journal articles, in 2002 Dr. Calabrese even published a greatly abbreviated, highly commercialized version, of his 1998 study (being careful to identify Lamotrigine by its GSK product title Lamictal) in an internet bulletin called “Fast Breaking Comments.” In this interview, Dr. Calabrese blatantly publicizes his determination that “lamotrigine (Lamictal) is effective in the treatment of patients with rapid cycling bipolar II disorder.” 7AC 0000439-0000441.
  1. To date, Lamictal has not received an indication for rapid cycling bipolar II disorder. However, GSK placed great emphasis on this study and sales representatives were expected to read and be familiar with Dr. Calabrese’s theories and statistics for use in off label marketing.
  1. Dr. Bowden began publishing his opinions concerning the efficacy of Lamictal in the treatment of bipolar disorder as early as 1998. Dr. Bowden became a widely sought after speaker for GSK, and GSK sales representatives nationwide were encouraged to try to persuade Dr. Bowden to make presentations on his findings in their geographical area.
  1. GSK’s Off-Label Marketing to Psychiatrists
  1. Seizure disorders – the only approved indication for Lamictal during the 1998 through 2003 period – were treated by neurologists, not psychiatrists. Notwithstanding that fact, GSK began requiring its sales representatives to detail Lamictal with psychiatrists and family practitioners many years before the approval for bipolar I disorder.
  1. It is clear that these ‘details,’ which were prevalent throughout the nation during this period, were directed at persuading physicians to prescribe Lamictal off-label for the treatment of bipolar disorder and through the use of free samples, ‘thought leader’ lunches, dinners and CME’s, and distribution of studies favorable to GSK, particularly the Calabrese 4612704 118 studies, GSK was extremely successful in persuading physicians to begin prescribing the drug off-label.
  1. As confirmation of the detailing of psychiatrists, a quick review of the contact sheets written up by the sales representatives shortly after the physician visits confirm the fact that the purpose of these visits was solely to market Lamictal for the treatment of bipolar disorders. The following is representative of the quantity of the off label physician visits by sales representatives including Ron Crews, Joan Schindler and Betty Hosler5
  • 9/13/00 Dr. Douglas Gregory (psychiatrist) ‘Had long discussion about Lamictal, is afraid of rash….Rash is severe side effect which has caused death in several patients….’Stevens Johnson Syndrome’….Gave him Calabrese article and encouraged him to talk to Marciniak [local GKS ‘thought leader’;
  • 10/18/00 Dr. McClure [Dr. Scott H. McClure, psychiatrist] Is getting more comf w/ lamic, thought it [conference put on by GSK]was informative More comfortable with Lamictal for bi-polar;
  • 10/26/00 Dr. Crandall (psychiatrist) “[D]iscussed Bowdens’ lecture, she is afraid of the rash;
  • 10/30/00 Dr. Gamblin (psychiatrist) ‘very pos. about lam. (Lamictal) has over 50 patients on it’…’Trained with Bowden sorry he missed it ‘ (referring to lecture in Colorado Springs that GSK arranged with Dr. Bowden as the speakers);
  • 10/30/00 Dr. McClure [Dr. Scott H. McClure, psychiatrist] ‘Said he is more comf.with Lamictal as monotherapy [in the treatment of bipolar disorder] after hearing Bowden likes the bottles of 25 only, not the kits (Lamictal) samples’;
  • 1/8/01 Dr. Harazin [Dr. Jeffrey Harazin, psychiatrist] ‘Lamictal is on it’s way’;
  • 03/21/01 Dr. Marciniak [psychiatrist] detailed by GSK District Manager for Lamictal in bipolar;
  • 05/23/01 Dr. Gregory [psychiatrist] attended noon lecture at Pikes Peak Mental Health with Dr. Paul Wender speaking, detailed on Lamictal;

5 These notes have been reproduced exactly as they were written in the contact reports by the individual sales representatives and entered into the Passport system following each sales call.

  • 06/12/01 Dr. Gamblin [psychiatrist] again detailed on Lamictal;
  • 06/19/01 Dr. Richard Marciniak [psychiatrist] detailed on Lamictal and offered a free fly fishing trip;
  • 06/21/01 Dr. Richard Marciniak again detailed on Lamictal and offered speaker/dinner engagement at local restaurant (Warehouse);
  • 07/05/01 Dr. Gamblin again detailed for Lamictal;
  • 07/19/01 Dr. Richard Marciniak again detailed on Lamictal and stated it is his choice for treatment of bipolar, as well as discussing dosage amounts and titration;
  • 07/30/01 Dr. Fred Michel detailed on the use of Lamictal for the treatment of children (‘Uses very little Lamictal in kids but would like to use it more.’);
  • 03/14/02 Dr. Julie Sanford [psychiatrist] detailed for using Lamictal in the treatment of bipolar;
  • 03/15/02 Dr. Gamblin had not yet seen the Calabrese study but did not want to drive to Denver for CME’s;
  • 03/15/02 Dr. James Spadoni [psychiatrist] detailed for the use of Lamictal in bipolar;
  • 03/19/02 Dr. Marciniak agreed to be paid by GSK to speak about Lamictal for bipolar as well as Wellbutrin at a lunch for local physicians in Colorado Springs;
  • 03/19/02 Dr. Stephen Mueller [psychiatrist] confirmed attendance at the bipolar/Lamictal physician’s meeting in Colorado Springs, Colorado;
  • 03/20/02 Dr. Gamblin again detailed for prescribing Lamictal for bipolar disorder;
  • 04/03/02 Dr. Marciniak detailed for Lamictal and confirmed that he would accept paid assignment to do GSK’s CME program on June 7, 2002;
  • 04/03/02 Dr. Spadoni [psychiatrist] detailed for use of Lamictal in bipolar disorder;
  • 04/10/02 Dr. Gamblin detailed for use of Lamictal in bipolar disorder with reference to the Calabreze study;
  • 04/24/02 Dr. David Caster [psychiatrist] detailed for Lamictal in bipolar disorder;
  • 04/25/02 Dr. Rosalyn Kneppel [psychiatrist] detailed for Lamictal in bipolar disorder;
  • 04/29/02 Dr. Nancy Sharpe, a Colorado Springs psychiatrist, was detailed for Lamictal in bipolar disorder; this doctor, who has a large Medicaid practice, asked the GSK sales representative about proper dosage amounts;
  • 05/01/02 Dr. Brian Grabert, a pediatric neurologist, was invited to be on GSK’s advisory board for an upcoming San Diego, California conference; 05/06/02 Dr. Gamblin detailed once again for Lamictal and now said he feels quite comfortable using it;
  • 05/08/02 Dr. Rosalyn Kneppel [psychiatrist] again detailed for Lamictal in bipolar disorder;
  • 05/08/02 Dr. Jeffrey Harazin again detailed for Lamictal in bipolar and now said he uses it ‘first line’ for bipolar disorder;
  • 05/13/02 Dr. Stephen Mueller, psychiatrist, again detailed for Lamictal in bipolar and requested pricing information;
  • 05/17/02 Dr. Marciniak agreed to do a talk and stated that he is using Lamictal more for bipolar now that he has more samples;
  • 05/20/02 Dr. Elliott Cohen, psychiatrist, detailed for Lamictal and he requested more samples;
  • 05/20/02 Dr. Rosalyn Kneppel [psychiatrist] again detailed for Lamictal in bipolar disorder and said she is using half the dosage [recommended for seizures] because of concerns about the rash;
  • 05/20/02 Dr. James Polo detailed for use of Lamictal in bipolar disorder in adolescents;
  • 05/22/02 Dr. Ralph Everett, child psychiatrist detailed for Lamictal in bipolar and after having stated he did not like it, was given a comparison to Zoloft by the GSK rep;
  • 05/22/02 Dr. Scott McClure, psychiatrist, again detailed for Lamictal in bipolar and Dr. McClure asked the GSK rep. how to dose if a patient was already on Depakote for bipolar and was given ‘the Calabrese study’ by the rep;
  • 05/23/02 Psychiatrists Dr. Anne League, Dr. James Spadoni and Dr. Julie Sanford were treated to lunch at a local Colorado Springs restaurant by the GSK sales representative and given American Psychiatric Association guidelines relating to Lamictal;
  • 05/23/02 Psychiatrist Pamela A. Brickers of Colorado Springs, CO was detailed by a GSK representative and was given a copy of ‘the calabrfese [sic] study’;
  • 05/29/02 Dr. Julie Sanford was detailed on Lamictal for bipolar and the GSK rep went over a study/comparison with Zoloft that was favorable to GSK’s product;
  • 05/29/02 Dr. James Spadoni and Dr. Richard Marciniak detailed for Lamictal;
  • 05/30/02 Dr. Brian Grabert detailed for Lamictal for his pediatric patients;
  • 06/05/02 Dr. Brian Grabert again detailed for Lamictal and discussed the rash;
  • 06/17/02 Dr. Honie Crandell again detailed for Lamictal in the treatment of bipolar disorder and confirms that it is her drug of choice for this disorder.
  1. In addition to targeting psychiatrists for detailing, prior to the FDA approved indication for bipolar I, GSK sales representatives were instructed to devote virtually all of their free sampling activities to psychiatrists, rather than neurologists. A routine practice that was documented in the contact reports of physician details as well as the first-hand experience of Relator Thorpe.
  1. GSK’S Off-Label Promotion of Lamictal Resulted in Patient Harm
  1. Although the FDA issued recommended dosing for Lamictal for its seizure indications, there were no such dosing guidelines for use in patients suffering from any form of bipolar disorder prior to the FDA approval in 2003. As such, there existed an acute risk of overdosing and resulting complications.
  1. Since the FDA did not establish a recommended dosage for Lamictal for use off label, and because the potential side effects were so severe if not dosed correctly, once the sales representatives had successfully gotten a physician to inquire about its use for bipolar, they were instructed to use the phrase ‘start low and go slow.’
  1. On information and belief, this “catchphrase” came directly from the GSK marketing department and was used by sales representatives throughout the country as a way to remind physicians to start with a small dose and raise the dosage very slowly in the treatment of bipolar I disorder in children and adolescents especially.
  1. Given the lack of dosing information, coupled with the intense campaign for use as a treatment for bipolar disorders, the contact reports referenced in the preceding paragraphs evidence physicians routinely inquiring about dosage and titration from the sales representatives themselves.
  1. On information and belief, as a direct and proximate result of the lack of proper dosing of Lamictal when used off-label, patients suffered both reported and unreported severe side effects including death.
  1. The Federal Drug and Cosmetic Act (“FDCA”) and its regulations require that adverse events due to prescription medications be promptly reported. However, ample evidence exists of widespread under-reporting of adverse drug reactions, even when drugs are being prescribed for their approved uses. (Mintzes, B., Bassett, K., Wright J.M.. Drug Safety without Borders: Concerns about Bupropion. Can. Med. Assoc. J., 2002;167(5); Moride Y, Haramburu F, Requejo AA, Begaud B. Under-reporting of Adverse Drug Reactions in General Practice. Br J Clin Pharmacol 1997;43(2):177-81; Bates DW. Drugs and Adverse Drug Reactions. How Worried Should We Be? JAMA 1998;279(15):1216-7; Okie, S., Safety in Numbers – Monitoring Risk in Approved Drugs, N.E.J.M., 352:1173-1176, March 2005.)
  1. On February 14, 2003, Relator Hamrick became aware of an incident involving the dangers of off-label prescription particularly when combined with the widespread laxity in adverse event reporting when he called on Dr. J. Vitanza, an allergist.
  1. Mr. Hamrick was informed that one of Dr. Vitanza’s patients had been prescribed Lamictal for bipolar I disorder (prior to its approval by the FDA) and noted in the patient’s chart an incidence of rash. Assuming that the patient’s psychiatrist would report the rash incident, Dr. Vitanza failed to report the occurrence to the FDA. After observing that the physician was not going to file an adverse event report, Mr. Hamrick filed his own, based upon his second-hand knowledge of the incident. 7AC 0000442-0000443.
  1. As a result of the underreporting of rash occurrences, physicians failed to be properly alerted to the potential danger of the rash which had, on a few occurrences, developed into Stevens-Johnson Syndrome.
  1. In addition to the unreported incidents of rash, often resulting from off-label prescriptions, at least one death resulted from the use Lamictal for bipolar I disorder.
  1. Dr. Julie Sanford, a psychiatrist who was consistently detailed by GSK sales representatives to prescribe Lamictal for bipolar disorders, prescribed the drug for a patient that subsequently died. Since Dr. Sanford was not a neurologist likely to be treating a patient for a seizure disorder, it should have been apparent to GSK officials receiving a copy of her adverse event report that the drug was, in all likelihood, prescribed for a non-indicated use.
  1. Nevertheless, in a May 22, 2001 letter to Dr. Sanford from GKS’s “Global Clinical Safety and Pharmacovigilance” division, there is a reiteration of adverse event reporting: the patient, who had been given Lamictal experienced headache and died, and other patients of whom she was aware also experienced rashes subsequent to receiving therapy with Lamictal. 7AC 0000444.
  1. Significantly, the “Global Clinical Safety and Pharmacovigilance” division, while allegedly interested ‘in obtaining as much information as possible concerning reports of suspected adverse reactions for the purpose of continuing to monitor and evaluate drug safety’ made no inquiry into the issue of the purpose of the supposed therapy.
  1. Of even more concern, in a conversation with Relator Thorpe, Dr. Sanford, a psychiatrist married to key opinion leader Dr. Marciniak, revealed that the patient who died was in fact being treated for bipolar I disorder.
  1. Clearly, when combined with the lack of recommended dosage, the off-label use of Lamictal made for a recklessly dangerous combination for patients resulting in severe rashes, including Stevens Johnson Syndrome, and even death.
  1. GSK Targeted Federal Health Care Programs for Off-Label Use
  1. GSK’s off-label marketing tactics also helped put their products on Tricare/Champus formularies for uses not approved by the FDA.
  1. For example, GSK focused on psychiatrist Dr. James Polo because of his position at Evans Army Hospital, Fort Carson, Colorado. As a result of the persistence of GSK, Lamictal was actually placed on formulary for treatment of bipolar disorders prior to receiving such an indication.
  1. GSK began seriously attempting to influence Dr. Polo in the late 1990’s by making arrangements for and paying for all of the food and liquor at the annual Colorado Spring Psychiatric Association Christmas party at Dr. Polo’s home, with 60-70 physicians in attendance.
  1. A simple review of just a few GSK contact reports in 2001 and 2002 clearly indicates that GSK sales representatives “detailed” Dr. Polo to enlist his aid in placing Lamictal on the Tricare/Champus formulary at Fort Carson for use in the treatment of bipolar disorders:
  • 4/23/02 Dr. James Polo detailed on Lamictal and Wellbutrin, invited to GSK speakers program, ‘he saw the green journal and asked if on lamictal on formulary, he said yes but for neurology only; he will champion it for p.t.’
  • 5/20/02 Dr. James Polo detailed on Lamictal with note ‘he was not attending the Tricare meeting this week, wsr for pts. w depression and concentration difficulties, lamictal is now a favorite of his and uses it in adol with bi-polar.’
  • 7/15/02 Dr. James Polo detailed on Lamictal and reported that ‘Lamictal is no longer restricted to neurology’ meaning it was now available on the Tricare formulary.
  • 07/24/02 Dr. James Polo detailed on Wellbutrin and Lamictal and reported “Lamictal free for all psyches.’
  1. As evidence of the success of the GSK engineered approval of Lamictal for use as a psychiatric treatment on the Fort Carson Tricare formulary, Dr. Kenneth Gamblin, a high volume Medicaid psychiatrist was told, (according to the July 17, 2002 GSK contact report) about availability of Lamictal on the Tricare formulary. Subsequently, according to the aforementioned contact report, he ‘…has started several new pts.’
  1. Upon information and belief, GSK targeted other high volume federal healthcare providers for off-label use of Lamictal and by the second quarter of 2007, Lamictal held a 14.1% share of the Medicaid market.”

 

Allen Frances ‘Replies’

BACKGROUND

On June 19, 2015, I published a post titled Allen Frances’ Ties to Johnson & Johnson.  In that post, I set out some very serious allegations against Dr. Frances.  I drew these allegations from a document titled Special Witness Report dated October 15, 2010.  The report was written by David Rothman, PhD, Professor of Social Medicine at Columbia College of Physicians and Surgeons.

Dr. Rothman’s report was produced in the context of a lawsuit filed by the State of Texas against Janssen Pharmaceutica, a subsidiary of Johnson & Johnson.

The allegations against Dr. Frances and two other psychiatrists, John Docherty, MD, and David Kahn, MD, arise from their production of an expert consensus schizophrenia treatment guidelines document.  The essential allegation is that Dr. Frances and his two partners violated, to a marked extent, the ordinary standards regarding conflicts of interest in the preparation and publicizing of the guidelines.

I quoted some passages from Dr. Rothman’s article, perhaps the most telling of which is the following:

“EKS [i.e., Drs. Frances, Docherty, and Kahn] wrote to Janssen on July 3, 1996 that it was pleased to respond to its request to ‘develop an information solution that will facilitate the implementation of expert guidelines.’…It assured the company:  ‘We are also committed to helping Janssen succeed in its effort to increase its market share and visibility in the payor, provider, and consumer communities.’”  [Emphasis added]

Paula Caplan, PhD, a clinical and research psychologist, and an Associate at Harvard’s DuBois Institute, had written an earlier article on this topic in Aporia.  Dr. Caplan had titled her article Diagnosisgate: Conflict of Interest at the Top of the Psychiatric Apparatus, and on March 6, 2015, Dr. Frances had published a very weak and ineffective rebuttal titled ‘Diagnosisgate’ Deconstructed and Debunked

. . . . . . . . . . . . . . . . 

Last Sunday, June 21, 2015, Dr. Frances tweeted to  me:  “Setting the record straight on careless claims” with a link to his earlier rebuttal.

So, to set the record straight:

Dr. Frances’s rebuttal did not address a single issue from the David Rothman report, and his tweeted claim that the rebuttal set the record straight is nothing short of fanciful. 

In my article, I challenged Dr. Frances to respond to two questions:

  1. Are the allegations against him and his EKS partners that are set out in detail in the David Rothman report accurate?
  1. Are the quotations in that report that are attributed to Dr. Frances accurate?

This challenge still stands.

The allegations against Dr. Frances are extremely serious, and in my view, comparable misconduct in reputable professions would result in censure, or even expulsion.  But with very few exceptions, the silence from psychiatry on this issue has been deafening, even though the David Rothman report has been in the public arena for almost five years.

At the present time Dr. Frances is presenting himself as the champion of moderation, and he routinely lays the blame for the overuse of psychiatric drugs on pharma marketing and on general practitioners.  But he has never, to the best of my knowledge, acknowledged that in the preparation and dissemination of the Tri-University Guidelines, he and his partners formed what they described as a “strategic partnership” with Janssen, and expressed a firm commitment to “helping Janssen succeed in its effort to increase its market share…”  And to guard against any misunderstandings, the issue here is not that Dr. Frances helped Janssen increase its market share.  The issue is that he did this in the guise of producing an objective treatment guidelines document.

Why aren’t psychiatrists screaming in protest?  Where is the outrage and censure?  Is psychiatry truly so intellectually and morally bankrupt that they will turn a blind eye to virtually anything, provided it expands psychiatric turf?

Allen Frances’ Ties to Johnson & Johnson

INTRODUCTION

I recently came across an article titled Diagnosisgate: Conflict of Interest at the Top of the Psychiatric Apparatus, by Paula Caplan, PhD.  The article was published in Aporia, the University of Ottawa nursing journal, in January 2015.  Aporia is “a peer-reviewed, bilingual, and open access journal dedicated to scholarly debates in nursing and the health sciences.”

Dr, Caplan is a clinical and research psychologist, and an Associate at Harvard’s DuBois Institute.  She worked as a consultant to the DSM-IV task force in the 1980’s, but resigned from this position after two years.    Here’s a quote from her February 2014 post on Mad in America The Great “Crazy” Cover-up: Harm Results from Rewriting the History of DSM:

“In the late 1980s, I was a consultant to two committees appointed by DSM-IV Task Force head Allen Frances to decide what DSM-IV should contain. I resigned from those committees after two years because I was appalled by the way I saw that good scientific research was often being ignored, distorted, or lied about and the way that junk science was being used as though it were of high quality . . . if that suited the aims of those in charge. I also resigned because I was increasingly learning that giving someone a psychiatric label was extremely unlikely to reduce their suffering but carried serious risks of harm, and when I had reported these concerns and examples of harm to those at the top, they had ignored or even publicly misrepresented the facts.”

Dr. Caplan has also written a brief synopsis of the Diagnosisgate article here.

PSYCHIATRISTS FOR HIRE

The central theme of Dr. Caplan’s 2015 article is that in 1995, Allen Frances, MD,  and two other psychiatrists (John Docherty and David Kahn) received grants of about $515,000 from Johnson & Johnson to write “Schizophrenia Practice Guidelines” which specifically promoted Risperdal (a Johnson & Johnson product) as the first line of treatment for schizophrenia.  The guidelines were called the “Tri-University Guidelines” in recognition of the fact that Dr. Frances worked at Duke, Dr. Docherty at Cornell; and Dr. Kahn at Columbia.  Subsequently, the three psychiatrists formed Expert Knowledge Systems, and from that platform, actively assisted Johnson & Johnson in the implementation and marketing of the guidelines.  For these latter services, J & J paid EKS a further $427,659.

The role of the three psychiatrists came to light because in 2004, the State of Texas filed a lawsuit against Janssen Pharmaceutica, a subsidiary of Johnson & Johnson, alleging that  company officials “targeted Texas Medicaid with their sophisticated and fraudulent marketing scheme” (here) to ensure that Risperdal was included in the state’s preferred drug list.

During these proceedings, an expert witness report was presented to the court by David Rothman, PhD, professor of Social Medicine at Columbia University College of Physicians and Surgeons.  The report is titled simply “Expert Witness Report” and is dated October 15, 2010.  The report, which can be found here, runs to 86 pages, and is meticulously detailed.

Here are some quotes from Dr. Caplan’s article:

“Allen Frances, arguably the world’s most powerful psychiatrist, spearheaded a massive, million-dollar project using psychiatric diagnosis to propel sales of a potent and dangerous drug by pharmaceutical giant Johnson & Johnson (J & J). Frances began the initiative in 1995, but his involvement has been little known, despite a court document written in 2010 that revealed what its author [David Rothman, PhD], an ethics specialist, called serious deception and corruption in that project.”

“According to the court document, Frances led the J & J enterprise that involved distortion of scientific evidence, conflicts of interest, and other illegal and unethical practices.”

“Rothman reported that, in 1995, the very year after DSM-IV appeared, Johnson & Johnson had paid more than half a million dollars (USD) to Frances and two of his psychiatrist colleagues to create an official-seeming document as the basis for promotion of one of their drugs. The following year, the drug company paid them almost another half million dollars to continue and expand the marketing campaign.”

“According to the Rothman report, Frances and his colleagues wrote guidelines that were designed specifically to persuade physicians to prescribe J & J’s drug Risperdal as the first line of treatment for schizophrenia.”

Here are some quotes from David Rothman’s report:

“In 1993, GTFH Public Relations echoed what State and Federal Associates [another PR company] had recommended the year before.  It, too, emphasized the need [for J & J]to cultivate state officials along with members of the psychiatric community…GTFH also emphasized that J&J should be convening Expert Task Force Meetings: ‘Formulate position and draft guidelines for consensus…Use: ‘Personalized invitational campaign to maximize participation.’…Finally, it counseled J&J to ‘Form exclusive partnership with growing advocacy group,’ citing NAMI as one case in point. J&J should help establish chapters and co-sponsor educational programs on patient issues…”(pp 13-14) [Emphasis added]

Note that one of GTFH’s recommendations was to “…draft guidelines…”

“As one of its first activities, and in disregard of professional medical ethics and principles of conflict of interest, in 1995 J&J funded a project led by three psychiatrists at three medical centers (Duke, Cornell, and Columbia) to formulate Schizophrenia Practice Guidelines.  From the start, the project subverted scientific integrity, appearing to be a purely scientific venture when it was at its core, a marketing venture for Risperdal.  In fact, the guidelines produced by this project would become the basis for the TMAP [Texas Medication Algorithm Project] algorithms, giving a market edge to the J&J products in Texas.” (p 14)

The production of the practice guidelines involved polling a selected sample of expert psychiatrists, and collating their questionnaire responses.

“The guideline team [Drs. Frances, Docherty, and Kahn] promised wide distribution of its product, including publication in a journal supplement.  The team was prepared to have J&J participate in its work, not keeping the company even at arms length.  With a disregard for conflict of interest and scientific integrity, the group shared its drafts with J&J.  On June 21, 1996, Frances wrote Lloyd [John Lloyd, J&J’s Director of Reimbursement Services]:  ‘We are moving into the back stretch and thought you would be interested in seeing the latest draft  of the guidelines project….Please make comments and suggestions.‘  (Italics added).  So too, the group was eager to cooperate with J&J in marketing activities.  Frances wrote without embarrassment or equivocation:  ‘We also need to get more specific on the size and composition of the target audience and how to integrate the publication and conferences with other marketing efforts”  (Italics added)…Indeed, from the start J&J had made it apparent to the team that this was a marketing venture.  In a letter to Frances, Lloyd set forth what he called an ‘aggressive time line’ for the project, and added:  ‘There are a number of other Treatment and Practice Guidelines for schizophrenia being developed or published during this same period that may well serve our marketing and implementation needs at a substantial lesser cost.’…” (p 15)

“Not only were Frances, Docherty and Kahn ready to violate standards of conflicts of interest in mixing guideline preparation with marketing for J&J, but also in publicizing the guidelines in coordination with J&J.  The three men established Expert Knowledge Systems (EKS).  The purpose of this organization was to use J&J money to market the guidelines and bring financial benefits to Frances, Docherty, and Kahn.” (p 15)

“EKS [i.e., Drs. Frances, Docherty, and Kahn] wrote to Janssen on July 3, 1996 that it was pleased to respond to its request to ‘develop an information solution that will facilitate the implementation of expert guidelines.’…It assured the company:  ‘We are also committed to helping Janssen succeed in its effort to increase its market share and visibility in the payor, provider, and consumer communities.’  Now that the ‘first phase’ was completed, with the guidelines created, ‘EKS is now ready to move forward in a strategic partnership with Janssen.’…The strategy will allow Janssen to ‘Influence state governments and providers….  Build brand loyalty and commitment with large groups of key providers around the country.’…EKS also promised ‘rapid implementations,’ with particular attention to having an impact on Texas decision making.’It is our intent to work with the State of Texas immediately in implementing this product in a select number of CMHC’s with the assistance of A. John Rush, MD.’…Again EKS emphasized:  ‘It is essential for Janssen to distinguish Risperidone [Risperdal] from other competitors in a timely and creditable way.’…In its Summary of the document, EKS wrote: ‘Your investment in the development of state of the art practice guidelines for schizophrenia is already beginning to pay off in terms of positive exposure in the Texas Implementation project.’…” (p 15-16) [Emphasis added]

Back to Paula Caplan’s article:

“On August 30, 2012, Texas Attorney General Abbott issued a press release to announce that Texas and 36 other states had together reached a settlement in which Janssen was to pay the states a total of $181 million because of its ‘unlawful and deceptive marketing.’  Here there appears another mystery: Interestingly, nowhere in either the filing or the press release did the names of Frances, Docherty, or Kahn appear, although their deceptive guidelines were the foundation for the enterprise, nor did they include the names of the other psychiatrists whom Janssen had hired to carry out the deceptive acts. Furthermore, they did not include information about harm done to the individuals who had been prescribed Risperdal.”

“Papers impelled by J & J were published in scholarly journals and, as Rothman reports, ghost-written by individuals selected by J & J, with high-profile names affixed as first authors after the articles had been written. These papers helped promote use of Risperdal to treat not only Schizophrenia but also Childhood Onset Schizophrenia, Schizo-affective Disorder, Bipolar Disorder in Children and Adults, Mania, Autism, Pervasive Developmental Disorder other than Autism, Conduct Disorder, Oppositional Defiant Disorder, Psychosis, Aggression Agitation, Dementia, below average IQ, and disruptive behavior. Subsequent to the production and marketing of the Tri-University Guidelines came the FDA approval of Risperdal to treat adults and then children diagnosed with Bipolar Disorder, and finally children diagnosed with Autism.”

And another quote from David Rothman:

“J&J turned the guidelines into a powerful marketing tool.  The slides presented at a CNS National Sales Meeting in March 1997, instructed employees to use the guidelines to convince its ‘Primary customers: P & T members [Pharmacy and Therapeutics committees], Formulary Decision Makers and Psychopharmacologists’ – those who made purchasing and reimbursement decisions – that they should use the guidelines to justify making Risperdal the drug of choice.…J&J also wanted the guidelines to promote the product’s use among ‘Secondary Customers,’ namely ‘Physicians who are not convinced of RISPERDAL’s 1st line status.’  So although the front piece for the guidelines described them as ‘suggestions for clinical practice,’ from J&J’s perspective, they provide ‘credibility; Reinforces RISPERDAL’s 1st line status; Differentiates RISPERDAL from convention[al] APS [antipsychotics] and other atypical APS.’  To make certain the customers got the message, the ‘Full Supplement [of the guidelines publication] should be left behind.’  J&J also funded CME offerings to publicize the guidelines, including a ‘Free ½ Day Seminars, Earn Up to 8 Hours of CE/CME.’  The panel of experts included Frances, Docherty, and Kahn, and also John Rush (who would play a key role in TMAP).  http://web.archive.org/web/19961106071503/www.ibh.com/expert1.htm” (p 17)

. . . . . . . . . . . . . . . . 

What’s particularly noteworthy in all of this is that since about 2010, Dr. Frances has been critiquing the obviously expansionist agenda of DSM-5, and the corruptive role of pharma in disease-mongering, and in the increasing over-use of psychiatric drugs.

In this context, he presents himself as the defender of moderation and scientific integrity, but, to the best of my knowledge, he has never publicly acknowledged his marketing role  with J & J in the creation of the Tri-University Guidelines.

ALLEN FRANCES REPLIES

On March 5, 2015, Dr. Frances did respond to Paula Caplan’s “Diagnosisgate” article.  Here are some quotes from this response, which appeared on the Huffington Post blog.  The quotes are interspersed with my comments.

“…in her usual dramatic and distorted way, Dr. Caplan feels she can score points and gain public attention by exposing a supposed, creatively named, ‘Diagnosisgate.'”

It is my general perception that when people respond to criticism with this kind of personal attack, they have something to hide.

. . . . . . . . . . . . . . . .

“Dr. Caplan, as always, is careless with facts, quick with misinterpretations, and filled with wild accusations. I will first debunk what is simple nonsense in her claims and then discuss the issues that do have a factual basis.”

“It is nonsense to state that my participation in guideline development was in any way a conflict of interest with DSM IV or affected in any way its preparation. The guideline project occurred several years after DSM IV was already in print. The term ‘Diagnosisgate’ is no more than Dr Caplan’s misleading attempt to attract an audience and has no connection to reality.”

There is no suggestion in Dr. Caplan’s article that Dr. Frances’s participation in the guideline development was a conflict of interest with DSM-IV.  In fact, Dr. Caplan notes that J & J’s first payment to Drs. Frances, Docherty, and Kahn occurred the year after DSM-IV was published.  What’s stressed in both Paula Caplan’s and David Rothman’s reports is the fact that Dr. Frances and his two co-founders of EKS actively collaborated with Johnson & Johnson in the marketing of Risperdal, and that the guidelines that they created were clearly designed for this purpose.

. . . . . . . . . . . . . . . .

“It is nonsense to imply that I made a great deal of money from DSM IV sales, which Dr. Caplan states totalled $100 million.”

There is no reference, or even implication, in Dr. Caplan’s article, that Dr. Frances made a great deal of money from DSM-IV sales.  Dr. Caplan mentions the fact that sales of the manual “earned more then $100 million”, but there is no suggestion that Dr. Frances shared in these profits.  Again, what’s stressed in both Paula Caplan’s and David Rothman’s articles is that Dr. Frances and his colleagues made about $900,000 from J & J for producing and marketing the Tri-University Guidelines.

. . . . . . . . . . . . . . . .

“It is nonsense for Dr. Caplan to claim there was ‘data distortion’ in either DSM IV or in the guidelines. Both efforts were the result of completely transparent and forthright processes. Both efforts had very clear and published methodological rules of the road that were conscientiously followed every step of the way.”

The phrase “data distortion” occurs in a sub-heading in Dr. Caplan’s synopsis article, but the phrase does not occur in her main article in Aporia.  So I’m not sure exactly what she had in mind.  But the notion that following one’s own “clear and published methodological rules of the road” guarantees validity and lack of bias is a little naïve.  All that Drs. Frances, Docherty, and Kahn would have to do to skew the results is, firstly, select questionnaire recipients whom they knew favored risperidone, and secondly, word the questions in a way that would tend to elicit the kind of responses that would promote risperidone.  In the published guideline document, the authors state that questionnaire participants were selected from several sources:

“…recent research publications and funded grants, the DSM-IV advisers for psychotic disorders, the Task Force for the American Psychiatric Association’s Practice Guideline for the Treatment of Patients with Schizophrenia, and those who have worked on other schizophrenia guidelines.” (p 2)

From this – obviously very large group – Dr. Frances and his partners selected 99 psychiatrists, 87 of whom responded to the questionnaire.  I can find no information as to how the 99 psychiatrists were selected.

. . . . . . . . . . . . . . . .

“She enjoys being the center of controversy and will always do her best to stir a tempest in a thimble.”

Ah!  That explains everything.

. . . . . . . . . . . . . . . .

But then, Dr. Frances acknowledges some retrospective misgivings:

“But in retrospect, there are two things about the project I much regret. Firstly, it was very unwise to do guidelines with drug industry funding. Even though they were fairly done, accurately reported, and contained built in methodological protections against industry-favorable bias, the industry sponsorship by itself created an understandable appearance of possible bias that might reduce faith in the sound advice and useful method contained in them. It was an error in judgment on my part that I apologize for. I have learned from my mistake and hope others do as well.”

So, there was absolutely nothing wrong with the guidelines, but the acceptance of pharma money may have created an appearance of bias.  And although no such bias existed, Dr. Frances is apologizing for creating this appearance.  But remember the EKS commitment quoted earlier:  “We are also committed to helping Janssen succeed in its effort to increase its market share and visibility in the payor, provider, and consumer communities.”  This is a clear statement of  bias.  It’s not an appearance of bias; it’s not possible bias.  It is out and out, unmitigated bias.  They express commitment, not to some improvement in client outcomes or welfare, but to increasing Janssen’s market share.  Drs. Frances, Docherty, and Kahn were hired to market Risperdal.  They were well paid, and they delivered what their employer expected of them.

And incidentally, despite his misgivings, there’s no indication that Dr. Frances has refunded his share of the $900,000 from J & J.  “May one be pardon’d and retain the offence?” (Hamlet, Act 3, Scene 3)

. . . . . . . . . . . . . . . .

“Secondly, I did not at the time anticipate, nor did the experts, that the atypical antipsychotics would be so frequent a cause of obesity and of the serious complications that follow from it. The considerable risks involved in using these new medications, and ways of avoiding these, were then unknown and not covered in the guideline.”

So, he assumed without evidence that the drug was safe unless proven dangerous, when in fact, good practice would be the opposite:  assume that the drug is dangerous, until it’s proven safe!  But, in any event, it wasn’t Dr. Frances’s fault.  After all, who could have known?

PUBLICATION OF THE GUIDLELINES

In 1996, the EKS’s Treatment of Schizophrenia guidelines were published as a 58-page supplement in The Journal of Clinical Psychiatry.  It’s an interesting document, and it certainly does promote the use of Risperdal (risperidone).  But of even more interest is this statement in the preface to the supplement .  It was written by Alan Gelenberg, MD, Editor in Chief of the journal.  Dr. Gelenberg begins the Preface with some words of praise for the guidelines, but also advocates caution with regards to pharma-funded projects:

“…in conditions such as bipolar disorder and schizophrenia, where the primary treatments are medications, industry is a looming presence.  Pharmaceutical companies devote enormous sums to academic departments and individual faculty members who consult, conduct research, and teach under the auspices of the company.  These then are the experts who create consensus guidelines.  While few of us sell our opinions to the highest bidder, fewer still are immune from financial influence.” [Emphasis added]

So Dr. Gelenberg could see these issues very clearly in 1996, when the guidelines were published; but Dr. Frances, despite his mea culpa in the Huffington Post last March, still hasn’t grasped the issue.  In that document, from which I quoted earlier, Dr. Frances contends that the guidelines “…contained built in methodological protections against industry-favorable bias…”.  But as Dr. Gelenberg so clearly points out, the expert consultants on whose opinions the guidelines were based were already subject to industry influence by the very fact of their status within the psychiatric community.  So, in fact, industry-favorable bias was actually built in.

Page 2 of the supplement lists the 87 expert psychiatrists on whose questionnaire responses the guidelines were based.  The list is in alphabetical order, and I checked the first fifteen names for links to pharma.  Two of the fifteen are deceased.  Of the remaining thirteen, nine have disclosed that they have received payments from pharmaceutical companies, and eight of these have received payments from Janssen Pharmaceutica/J & J.

I have no way of checking if these financial links were present in 1995/96 when the guidelines were produced, but the extent of these individuals’ involvement with pharma today suggest that Dr. Gelenberg’s concerns were probably well founded.

. . . . . . . . . . . . . . . .

On the supplement’s sub-cover there is a brief acknowledgement of Janssen’s funding:

“This project was supported by an unrestricted educational grant from Janssen Pharmaceutica.”

The term “unrestricted” has a very specific meaning in this context.  It means that the recipients of the grant are not required to produce any particular result.  Essentially there is an expectation that both grantor and recipient will take steps to keep one another at arms’ length.  The term “unrestricted” is, in a sense, a warranty to the reader that the document in question is free from funder bias.

In the light of the material quoted above, it strikes me that the description “unrestricted” in this case was at best misleading, and possibly a blatant deception.

A CHALLENGE TO DR. FRANCES

If Dr. Frances really wants to put this matter to rest, he needs to answer these questions publicly and unambiguously:

  1. Are the allegations against him and his EKS partners that are set out in detail in the David Rothman report accurate?
  1. Are the quotations in that report that are attributed to Dr. Frances accurate?

If the answer to both of these questions is No, then I suggest that Dr. Frances start devoting his time and energy to addressing these matters, and clearing his name, because the allegations are very serious.

But if the answer to one or both of these questions is Yes, then I respectfully suggest that Dr. Frances exit the stage with whatever dignity he can muster, and resume his well-earned retirement.

AND INCIDENTALLY

Mickey Nardo, MD, has also posted David Rothman’s report on his website, 1 Boring Old Man.  Dr. Nardo has also written a post on this topic.  The post is titled detestable.

. . . . . . . . . . . . . . . .

I have quoted from David Rothman’s report in this post, but I’ve confined my attention to material concerning Dr. Frances and EKS.  In fact, the report covers a lot more ground, and gives a great deal of detail on the pharma-psychiatry corruption that has marred the landscape in this field for so long.  It’s well worth reading.

For instance, here’s an insightful little gem from page 21:

“Shon [Steven Shon MD, Medical Director of the Texas Department of Mental Health and Mental Retardation] was also considered a pivotal figure by another J&J employee, Percy Coard…After thanking his colleagues for attending a Shon presentation, he listed all the reasons why J&J wanted a ‘strategic alliance’ with him.  As Coard explained, Shon was a KOL [key opinion leader], influential in the public sector, where ’85 Percent of all anti-psychotic dollars come from;’ he has influenced and supported the use of new drugs in TMAP [Texas Medication Algorithm Project], and a proactive approach to him ‘to support/partner with his current and future projects in the public sector arena will continue to position Janssen as a true partner in public mental health initiatives.'”

Such a sense of civic responsibility!

. . . . . . . . . . . . . . . .

Robert Whitaker discusses EKS and the Tri-University Guidelines in his latest book, Psychiatry Under the Influence, p 149-150.

FINALLY

And for anyone who has any doubts concerning the effectiveness of pharma-psychiatry’s marketing machine, here’s a graph produced by the Agency for Healthcare Research and Quality (AHRQ), a division of the US Department of Health and Human Services.

AHRQ fig 1 on antipsychotics

So between 1997 and 2007, total expenses for neuroleptic drugs in the US went from $1.7 billion (corrected to 2007 value) to $7.4 billion.  This is an increase of $5.7 billion over and above any increase due to inflation.

The cost of these extra sales in terms of reduced life expectancy and quality of life is psychiatry’s legacy to humanity.

Neuroleptic Drugs And Mortality

In November of last year, the Schizophrenia Bulletin published online a research study:  Antipsychotic Treatment and Mortality in Schizophrenia, by Minna Torniainen et al.  The research was conducted in Sweden.

The authors offer the following background for the study:

“It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view.”

and the following conclusions:

“Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.”

On the face of it, this finding would seem to upset the notion, widely accepted in antipsychiatry circles, that neuroleptic drugs are toxic, and that their use, especially prolonged use, markedly reduces life expectancy.  There are, however, some problems with the study that need to be considered.

First, let’s take a look at one of the graphs presented in the article.

Torniainen fig 1 upper half

 

 

 

 

 

 

 

 

Fig. 1.  (a) Overall mortality as hazard ratios in the chronic patient population (N = 21 492) compared with mortality in the control sample.

What we see graphed here are the mortality figures for the four groups identified and followed in the study.

  • participants with no exposure to neuroleptic drugs
  • those with low exposure
  • those with moderate exposure
  • those with high exposure

Mortality is presented as a hazard ratio compared to matched pairs in a control sample.

The actual numbers are:

Tornianen hazard ratio chart

 

 

 

 

 

So the individuals with no neuroleptic exposure had 6.3 times the death rate as their matched controls.  The low exposure group, 4.06, and so on.

The black vertical lines through each graph value represent the 95% confidence interval for that value.  What this means is that we can be 95% confident that the true value of each hazard ratio lies within the range of the vertical black line.  Note that the confidence interval is widest for the zero use group.  This is because they were numerically the smallest group.

The numbers of people who died in each group were:

Tornianen study Death rates

 

 

 

 

Total sample size was 21,492, and the results appear to confirm the authors’ conclusions: that the mortality rates for people “diagnosed with schizophrenia” bear a U-shaped relationship to neuroleptic use, with the highest rates associated with both zero and high use.

. . . . . . . . . . . . . . . .

Note that two comparisons were made.  Firstly, all the individuals labeled schizophrenic were compared to the “control sample”, and secondly within the “schizophrenia” group comparisons were made between the four sub-groups:  zero, low, moderate, and high users of neuroleptic drugs.

For comparative research of this sort to be valid, there is a fundamental requirement that the target group has to be essentially similar to the comparison group in every respect, except the characteristic under study, which in this case is, firstly, the presence of a “diagnosis of schizophrenia,” and secondly, the degree of neuroleptic exposure.

The importance of this assumption can be readily appreciated by an example.  Suppose that all the members of the zero-neuroleptics group in this study had a history of heart problems, and none of those taking the drugs had such problems.  Clearly, the conclusion would be flawed because a group of people with heart problems will, other things being equal, have a higher mortality rate than people without such problems.

It is to counter such problems that researchers use double-blinded randomized controlled trials (DBRCT’s).  In a DBRCT, study participants are recruited, and are randomly assigned to receive either a treatment or a placebo.  The treatment provider, the client, and the person who is rating the outcome are “blinded” – i.e. they don’t know which participants have received the treatment and which have received the placebo.

The randomization process allows us to be reasonably, but not totally, certain that the two groups are sufficiently similar to allow comparisons to be made.

The study under consideration here was not a DBRCT.  It was an observational, matched pairs study.  Here’s how the authors describe their methods:

“We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 (N = 21 492), aged 17–65 years, and persons with first-episode schizophrenia during the follow-up 2006–2010 (N = 1230). Patient information was prospectively collected through nationwide registers.  Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010.”

The study is observational in that the authors simply identified all individuals in Sweden with “schizophrenia diagnoses” prior to 2006 and individuals who had a first-episode of psychosis and a “diagnosis of schizophrenia” between 2006 and 2010.  They then searched death registers and drug prescription registers to observe and document mortality rates for zero, low, moderate, and high users of neuroleptic drugs.

As mentioned earlier, the study entailed two different comparisons – mortality rates for individuals labeled “with schizophrenia” were compared to rates for the control sample; and within the “schizophrenia” groups mortality rates were compared for zero, low, moderate, and high neuroleptic users.

The control groups for the first comparison consisted of  “…age- and gender-matched controls from the general population…”

“The mortality in persons with schizophrenia was compared with a control sample from the general population.  For each person with schizophrenia, we identified 10 age- and sex-matched persons without schizophrenia.”

The results for the first comparison were:

Tornianen first comparison.

The authors don’t tell us exactly how the matched controls were selected.  All we know is that for each member of the “schizophrenia” group there were ten controls of the same age and gender who did not “have schizophrenia”.  This was a total of 214,670 individuals.

There are two problems with this approach.  Firstly, no amount of matching of this sort can produce truly comparable groups.  The reader has only to bring to mind people of the same age and gender as him/herself to realize that the differences will outweigh the similarities.  Using ten controls for each study participant does improve the situation somewhat, in that the resulting averaging will tend to smooth out extreme differences, but the problem is by no means eliminated.

Secondly, “schizophrenia” is a notoriously unreliable label.  The DSM-5 trials yielded Kappa scores of only 0.46.  What this means essentially is that, of the 21,492 participants labeled as “having schizophrenia”, a substantial number would not be so labeled if examined by an independent psychiatrist.

Matched-pairs studies can be useful in general medicine, where the number and the nature of confounding variables are often relatively limited.  But they are problematic in psychological/behavioral research because of the inherent complexity of the subject matter and the almost infinite range of potential confounders.

MORTALITY RATES AND NEUROLEPTIC USE

As mentioned earlier, the graph and the hazard ratios would appear to confirm the authors’ conclusion that the zero-users had the highest mortality rate.  However, there are a number of observations that need to be made.

1.  There is normally a great deal of pressure on people who receive “a diagnosis of schizophrenia” to take neuroleptic drugs. From the numbers presented in the study, 2077 of the 21,492 participants took no neuroleptics.  So, either the treating psychiatrists did not prescribe the drugs, or the individuals refused to take them.  In either event, I think it is clear that these individuals, taken as a group, are dissimilar from those individuals who did take the drugs.  In the absence of more detailed information about these individuals, it is not safe to attribute their excess mortality to the fact that they didn’t take the neuroleptics.  Indeed, the authors acknowledge this:

“Because the nature of this study is observational, the associations may not necessarily mean causality. The results concerning comparative mortality between different exposure groups did not change substantially when the clinical and sociodemographic characteristics were controlled in the secondary analysis within the patient population. However, it is not possible to fully adjust for the severity of the illness and lifestyle characteristics by using such databases, which do not include information on smoking or diet, for example. Disease may be more severe in patients with high medication use than in patients with moderate antipsychotic use, and therefore the higher mortality in this group may partially derive from disease severity.”

But, by exactly the same token, some unidentified extraneous factor may be at work within the zero-use group and may account for their higher mortality rate.

2.  The zero-use individuals may not have been truly zero-use.

“…because antipsychotic medications that may be used in hospitals are not recorded in the Prescribed Drug Register.”

“…no information was available on the use of medication during the hospital treatment days…”

3.  The finding that “the highest overall mortality was observed among patients with low antipsychotic exposure…” is an over-simplification.  In fact, some of these individuals had a particularly low hazard ratio, while others had a particularly high  hazard ratio.  This can be seen clearly in Table 3:

Torniainen Table 3

In this table the moderate use group is used as the reference point.  This is why all the hazard ratios for that group are 1.  Hazard ratios for the other exposure groups are calculated as compared to the moderate group.

Here again, we see (top line) that the highest overall hazard ratio is for the zero-use group (1.56); next the high-exposure group (1.43); then the low-exposure group (0.97).  The actual numbers differ from the earlier hazard ratios because those were calculated in reference to the matched controls, whereas the ratios in Table 3 are calculated in reference to the moderate-use group

Although the authors were unable to obtain information on drug prescriptions during hospital stays, they were able to determine whether a participant had been hospitalized and when.  This is why they were able to calculate the hazard ratios for individuals who had had inpatient treatment prior to the follow-up period.  Note that the hazard ratios for zero-users who had had previous inpatient treatment are high:  3.46 for people who had had treatment within the year prior to follow-up and 1.69 for those who had inpatient treatment earlier.  And also note that the hazard ratio for the zero-users who had had no treatment, but were identified only from disability pension rolls, is relatively low:  1.06.  The hazard ratio for the high users in the same category is 2.19.  So the authors’ conclusion that the highest risk of death was “among those patients with no antipsychotic use”, is not the whole truth.  The group with the highest risk consists of those individuals who had zero exposure to the drugs and who had had inpatient treatment within the previous year.  The zero exposure individuals who had no record of formal treatment had a much lower risk ratio (1.06).  This, of course, doesn’t prove that treatment is causing excess mortality, but it is at least as noteworthy as the U-shaped curve highlighted in the authors’ conclusion.

4.  As indicated earlier, it is widely accepted that prolonged use of neuroleptic drugs reduces life expectancy, and that these toxic effects continue to impact mortality rates as long as the individual continues to take the drugs. To adequately monitor and study this effect, it is, I suggest, particularly important to include older people in the research.  In this study, however, only individuals below the age of 65 were included.  This will almost certainly have the effect of artificially lowering the mortality rate for the neuroleptic users.  The senior years are precisely the time when one would expect to see the toxic effects of a drug become most evident.  The authors provide no rationale for setting this upper age-limit.

5.  The total number of deaths in this study was 1591. Causes of death were given as follows:

Tornianen causes of death charge

 

 

 

 

This leaves 483 deaths unaccounted for.  The authors tell us how the 1,108 deaths break down by exposure category, but we are given no information on the other 483 deaths.  This is 30% of the total.  We don’t know how these people died, nor how their deaths were distributed among the four exposure groups.

I wrote to Jari Tiihonen, the correspondence author, for information on this matter.  In his reply, Dr. Tiihonen stated that this information was not available.  It is possible that the 483 “missing” deaths were distributed across a large number of relatively low frequency causes.  Studies of this kind often use an “Other Cause” category to capture this information.  The complete absence of information on these deaths in this study, however, is noteworthy.

6.  Perhaps the most serious problem with the study lies in the method that was used to define the four exposure groups. Let’s go back to a statement made in the “methods” section of the abstract:

“Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010.”

My initial interpretation of this sentence, and I think it’s the interpretation that most people would make, is that mortalities were calculated during the follow-up period 2006-2010, and these mortalities were compared to lifetime cumulative drug exposure.  In fact, as becomes clear later in the text, this is not what was done.

“The identified schizophrenia patients were categorized into 4 DDD groups; (1) no antipsychotics during the follow-up, (2) small doses of antipsychotics or occasional use (0 DDD/ day–0.5 DDD/day, noninclusive), (3) moderate doses of antipsychotics (0.5 DDD/day–1.5 DDD/day, inclusive), and (4) high antipsychotic doses (>1.5 DDD/day).” [Emphasis added]

So the individuals in the study were categorized – not by cumulative lifetime exposure to neuroleptics, but only by exposure during the five-year follow-up period.  For example, a person who had been taking neuroleptics for decades, and came off the drugs in December 2005, and died in January 2006, would have been recorded as a mortality in the zero neuroleptic exposure group.

The phrase “cumulative antipsychotic exposure”, which occurs five times in the article, suggests lifetime exposure, and in my view the authors did not adequately emphasize the fact that the exposure data was actually limited to a five-year period.  This strikes me as particularly pertinent, in that it is precisely the long-term cumulative exposure to these drugs that is the primary cause of the mortality concerns.  The fact is that the present study provides no information on the effects of cumulative lifetime exposure to neuroleptic drugs.

PRESENTATION OF DATA

Here’s a copy of the authors’ Figure 2.

Torniainen Fig 2

Fig. 2.  Mortality expressed as hazard ratios due to specific causes in patients with schizophrenia compared with the control sample.

The mortality figures for respiratory illnesses show a generally upward progression from zero-use to high use.  Figures for the other causes of death (cardiovascular, neoplasms, and suicide) show zero-use higher, or nearly as high, as high-use.  But look at the scales on the left of each figure.  The respiratory scale, which shows the neuroleptics in the worst light, is the tightest, and the cardiovascular scale, which shows zero use in the worst light, is the loosest.  Here’s what the data looks like when all causes of death are graphed on the same figure and on the same scale.

Tornianen Mortality composite change data

As can be seen, the U-shape becomes a good deal less evident.  The neoplasm line is fairly flat.  The death rate for respiratory illnesses is increasing markedly with increased drug use.  The suicide rate is sloping in the opposite direction.  Only the cardiovascular line is identifiably U-shaped:  a finding for which I can suggest no particular explanation, though it does seem unlikely that it reflects a lack of neuroleptic drugs.  More likely, it reflects the fact that the zero use group were not really zero use.

AUTHORS’ CONCLUSIONS

The conclusions from the abstract were quoted earlier, but there is a more detailed conclusions section in the text of the article.

“Patients with low or moderate antipsychotic exposure have substantially lower overall and cardiovascular mortality than patients with no exposure or high exposure, which clearly indicates that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than long-term antipsychotic treatment when used in adequate dosages. An alarmingly high excess mortality among first-episode patients who do not use any antipsychotics deserves more attention, in order to increase adherence to their prescribed pharmacological treatment. Despite the importance of nonadherence, clinicians spend too little time on addressing this issue. For example, long-acting antipsychotic injections (LAIs) are associated with about 60% lower all-cause discontinuation than corresponding oral formulations among first-episode patients.  Thus, more use of LAIs might result in substantially lower excess mortality.  Focusing more attention particularly on first-episode and recently hospitalized patients who are not using any antipsychotics, and on patients with antipsychotic doses higher than 1.5 DDD/day, is essentially important in the prevention of premature death in people with schizophrenia.”

And there it is:  people who don’t use the drugs have higher mortality, so steps must be taken to ensure adherence.  And this conclusion is being promoted even though the identification of individuals with zero cumulative exposure was seriously flawed and unreliable.

AND INCIDENTALLY

The final author listed in the article is Jari Tiihonen.  Dr. Tiihonen works for the Department of Mental Health and Substance Abuse Services in Finland; the Department of Clinical Neuroscience, Karolinska Institutet, Sweden; and is Professor and Chairman, Department of Forensic Psychiatry, University of Eastern Finland.

Though he is not identified as such, it is fairly clear that Dr. Tiihonen is the senior investigator in the present study.  He is identified as the correspondence author, and he is the Team Leader of the Center for Psychiatric Research at the Karolinska Institutet.

In the present paper it is acknowledged:

“In the last 3 years J.T. [Jari Tiihonen] reports serving as a consultant to Lundbeck, Organon, Janssen-Cilag, Eli Lilly, AstraZeneca, F. Hoffman-La Roche, and Bristol-Myers Squibb; he has also received fees for giving expert opinions to Bristol-Myers Squibb and GlaxoSmithKline, and lecture fees from Janssen-Cilag, Bristol-Myers Squibb, Eli Lilly, Pfizer, Lundbeck, GlaxoSmithKline, AstraZeneca, and Novartis; he is also a member on the advisory board of AstraZeneca, Janssen-Cilag, and Otsuka, and he has received a grant from the Stanley Foundation.”

CITATIONS

The article didn’t attract a great deal of attention.  But I did find three interesting citations.

Joel Yager, MD, psychiatrist, writing in the NEJM Journal Watch wrote:

“Even though this observational study cannot prove causality, the notably higher mortality among patients with no antipsychotic exposure suggests that adherence-increasing interventions, including use of long-acting injectable medications, might reduce risk for death.” [Emphasis added]

And schizophrenia.com:

Antipsychotic Treatment and Mortality in Schizophrenia: No Drugs = Higher Mortality

And Joanna Lyford writing on Medwire News:

“The relationship between antipsychotic use and mortality in people with schizophrenia shows a clear U-shape curve, with the highest risk of death seen in those with no antipsychotic exposure, a Swedish cohort study has found.” [Emphasis added]

None of the articles mentioned the fact that the results applied only to those individuals who had received prior treatment (particularly inpatient treatment), and was not evident at all in people with no record of treatment.  Nor did any of the articles mention the fact that the “cumulative antipsychotic exposure” applied only to the five-year follow-up period, and that neuroleptic use prior to that period was not considered.

Antidepressant Drugs and Suicide Rates

In 2010, Acta Psychiatrica Scandinavica published a study by Göran Isacsson et al.  The paper was titled Antidepressant medication prevents suicide in depression.  Here’s the conclusion:

“The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.”

It’s a complicated article, with some tenuous logic, but note in particular the contrast between the fairly cautious wording in the conclusion, and the bold, even brazen, assertion in the title.

But, in any event, it’s all moot, because the article was retracted by the authors and by Acta Psychiatrica Scandinavica about sixteen months after publication.  The retraction had been requested by the authors because of “…unintentional errors in the analysis of the data…”

The research in question was conducted in Sweden.  Dr. Isacsson works at the Division of Psychiatry in the Karolinska Institutet, Stockholm.  He has been writing since at least 1994 on the putative efficacy of antidepressants in the prevention of suicide.

The 2012 retraction notice did not attract as much attention as the original article, but it did stimulate a measure of discussion.  Mickey Nardo wrote posts on the subject, here, here and here.  Bob Fiddaman wrote a post here, and Ivan Oransky of Retraction Watch wrote on the matter here.  Ivan reported that he had contacted Dr. Isacsson and Acta Psychiatrica Scandinavica for more information, and received the following reply from Dr. Isacsson:

“We discovered lately that there was a coding error regarding diagnoses in the database we utilized for the 2010 paper. When corrected, antidepressants were detected in depressed suicides as often as could be expected and not less than expected which was the crucial finding in the paper. This means that no conclusion can be drawn from the study regarding antidepressants’ effects on suicide risk in any direction.

The database has not been used for other studies so no other papers are affected.”

Jan Larsson, a Swedish journalist, wrote an interesting article on the matter.  Here’s an extended quote: 

“Isacsson’s findings from 2010 were widely published in Swedish newspapers, with headlines like  ‘Antidepressants prevent suicide’ (Dagens Nyheter), where it was said: ‘He [Isacsson] means that many become provoked to hear that depression is a deadly disease and that suicides can be prevented with medicines’. And, said Isacsson: ‘Therefore, it is important to show that antidepressants actually prevent suicide.’

In June 2012 I made an FOI request to Karolinska Institutet (where Isacsson is working) to get the corrected figures in this research project. I specifically wanted to get the document containing the correct percentage of antidepressants for those ‘who committed suicide and who had previously been treated at a psychiatric clinic for depression’ (the earlier mentioned group of 1077 persons).

The answer from Karolinska Institutet: This is confidential information, no data can be released.

It took a five month legal process to get access to the correct data. During this whole process Karolinska Institutet claimed that all the data in this research project were confidential.

In a final statement to the court, after having to answer specific questions, Karolinska Institutet stated that the correct figures did not exist at the time of the FOI-request – remember that they were said to be confidential at the time – but that the correct figures now had been produced.

Karolinska Institutet stated to the court: ‘that information has now been produced … The result shows that ‘the correct percentage’ is 56, meaning that of the persons who had been treated for depression in psychiatric care in the last five years before suicide, 56% had antidepressants in their blood when they committed suicide.’

So finally we got to know that the 15.2% in actual fact was 56% – an increase of 268% (from 164 persons to 603).

We had a seven pages long scientific article, with great impact in media, where doctors and the public got the message that antidepressants protect against suicide – an article built on Isacsson’s faulty finding that only 15.2% in the group had antidepressants in their blood when they committed suicide. And so the correct data, which completely defeated Isacsson’s speculations and conclusions in the original article, ‘published’ in a short statement to the court in Stockholm, where no doctor, no patient and no other researcher could find it.”

So, Dr. Isacsson et al’s original finding of 15.2% was a very large error indeed.  As I mentioned earlier, the logic underlying the study is tenuous, but Table 1 from the study will provide some insight into the authors’ thinking.

Isacsson Table 1

The controls (34,165) are people who did not commit suicide.  These are individuals who died from accidental and natural deaths.  Antidepressants were detected in 6.5% of these individuals post-mortem.

The suicides (18,922) represent all Swedish suicides from 1992 to 2003.  Antidepressants were detected in 22.4% of these people post-mortem.

Then the authors broke the numbers down further.  They note that 11,226 of the suicides had no psychiatric hospitalization in the 5 years prior to their deaths.  Of these individuals, 14.8% had antidepressants detected post-mortem.  The remaining 7,696 suicides, who had been in a psychiatric hospital in the preceding 5 years, had an antidepressant detection rate of 33.6%.

And this is where it gets complicated.  The researchers broke the hospitalized numbers down further, into:

  • Those hospitalized for depression only                              15.2%
  • Those hospitalized for other problems                               37.3%
  • Those hospitalized for depression plus other problems    33.2%

Their argument was that the first group (depression only) would be expected to have about the same, or an even higher, level of detected antidepressants as the other groups.  But, contrary to expectations, they found that they had the lowest level – about the same, in fact, as the group who had not been hospitalized in the previous five years.

So, they reason that large numbers of the hospitalized-for-depression-only group, most of whom presumably had antidepressants in their blood stream, had “been saved from committing suicide by antidepressant treatment.”

But as mentioned earlier, there was an error in the data, and the correct number was 56%.

Now all of this is well-known, but there is an aspect of the matter that has not, to my knowledge, been addressed previously.  Let’s go back to Dr. Isacsson’s letter to Retraction Watch.

“We discovered lately that there was a coding error regarding diagnoses in the database we utilized for the 2010 paper. When corrected, antidepressants were detected in depressed suicides as often as could be expected and not less than expected which was the crucial finding in the paper. This means that no conclusion can be drawn from the study regarding antidepressants’ effects on suicide risk in any direction.

The database has not been used for other studies so no other papers are affected.”

Dr. Isacsson is saying that antidepressants were detected in the depression-only suicides “as often as could be expected and not less than expected.”

Strictly speaking this is true.  56% is not less than 15%.  But the statement is also deceptive, in that 56% is a great deal more than 15%.  The difference in the study in question is 439 people.

Dr. Isacsson issued the above statement on March 19, 2012.  At that time, neither he nor Karolinska Institutet had released the 56% figure (on the patently spurious grounds of confidentiality).  It took several more months of legal process before the 56% figure was produced.  So at the time that Dr. Isacsson wrote  “…not less than expected…”, he probably did not anticipate that the true figure would ever be released.

But the plot thickens even further:

“This means that no conclusion can be drawn from the study regarding antidepressants’ effects on suicide risk in any direction.” [Emphasis added]

If a particularly low number (15%) warrants the conclusion in the article’s title (“Antidepressants medication prevents suicide in depression”), wouldn’t it be reasonable to infer that a particularly high number (56%) might warrant the opposite conclusion?  This is particularly so in that the increase from 15% to 56% can only have come at the expense of one or other of the remaining categories, which would make the discrepancy even larger.

I’m perfectly willing to accept that the original analysis was a genuine error.  But at the time of the retraction and the letter to Retraction Watch, Dr. Isacsson must have known that the true figure was 56%, and the question needs to be asked:  Why did he not release the 56% figure voluntarily at the time of discovery?  In addition, it is difficult to avoid the conclusion that his letter to Ivan Oransky was deliberately deceptive.  Mickey Nardo puts the matter well:

“It would be easy to drift into a debate about the relationship between suicide and antidepressants and miss the point here, which is that medical opinion should follow science, not the other way around. It’s clear that Göran Isacsson is of the opinion that antidepressants should be given to decrease the incidence of suicide – he has an absolute right to express that opinion. But when Isacsson offers as proof of his opinion a published study of the Swedish public records, and it turns out that his data either is wrong, not to be found, or never existed in the first place, we have to conclude that Göran Isacsson is an ideologue and has no place in the psychiatric literature.”

At the time of writing the article in question, Dr. Isacsson had financial ties to Lundbeck, Eli Lilly, and GSK.

INCIDENTALLY

Dr. Isacsson not only continues to promote the notion that wider use of antidepressant drugs will prevent suicides, but he also calls routinely for the removal of the FDA’s black box warning on this matter (e.g.  here).

In June 2010, the British Journal of Psychiatry published a debate on the topic:  The increased use of antidepressants has contributed to the worldwide reduction in suicide rates.  Arguing for the notion were Dr. Isacsson and Charles L. Rich, MD, Professor Emeritus of Psychiatry, University of South Alabama; arguing against were Jon Jureidini, MD, child psychiatrist at the Women’s and Children’s Hospital, Adelaide, and Melissa Raven, PhD, Research Fellow at Flinders University. Adelaide.

The debate effectively discredits Dr. Isacsson’s position, and is well worth reading.

Pharma-funded Research

On August 20, 2014, Psychiatry Advisor published an article on its website.  The article was written by Leslie Citrome, MD, a professor of psychiatry at New York Medical College in Valhalla, NY, and a member of the Board of Directors of the American Society of Clinical Psychopharmacology.  The article is called Is Bias Against Pharma-Funded Research Fair?  This is an interesting title, because bias, by its very definition, is unfair.  So the very wording of the question begs the question – which strikes me as unfair.  But let’s put that aside. 

Dr. Citrome begins by introducing the term “pharmaism” (anti-pharma prejudice).  He tells us that:

“Pharmaism includes the implicit belief that people associated with pharmaceutical companies are more likely to be intellectually and morally dishonest than others.”

He provides two examples of pharmaism:

The fact that medical journals insist on independent statistical analyses of research submitted by pharmaceutical companies.

“…the lay media singling out health-care professionals who earn money by contracting with pharmaceutical companies for professional services…”

Dr. Citrome predicts, with apparent misgivings, that the media’s activities in this area will increase when the Physician Payments Sunshine Act’s provisions take effect on September 30.

So, as you can see, the article is off to a good start.  Medical journals that insist on independent statistical analyses of pharma-conducted research are displaying prejudice against pharmaceutical companies.  And we even have a name for this prejudice – “pharmaism,” akin, presumably to racism.

But, wait!  There’s an important difference.  Racism refers to prejudice or discrimination against another person, or group, based solely on race or skin color.  But medical journals that insist on independent statistical analyses of pharma-conducted research are basing this policy decision on the fact that, in a compellingly large proportion of cases in the past, the statistical analyses of pharma-funded research was flawed.  And, by an extraordinary coincidence, was always flawed in a direction favorable to the company!

What Dr. Citrome is trying to do is rescue both pharma and the psychiatrists who accepted their largesse, from the consequences of their venality.  Psychiatry maintained its corrupt relationship with pharma for decades.  The dynamics were simple.  Pharma provided the money; psychiatry provided the fraudulent research, the medical licenses, and the prescription pads.

But now the hoax has been exposed, and corrective measures have been taken.  And Dr. Citrome is crying:  foul!  You people are just pharmaists!  A nice piece of spin, which, incidentally, in prison populations is called “flip the script”.

To find a psychiatrist using a ploy that is popular among prison inmates is not all that surprising to me.  But, you see, I’m a pharmaist – so what can you expect?

Incidentally, the term pharmaism was actually coined by Dr. Citrome, himself, and James Karagianis, MD.  Here’s a quote from the June 2014 issue of The International Journal of Clinical Practice editorial Pharmaism: a tale of two perspectives, by L. Citrome, et al.

“The term ‘pharmaism’ (or ‘pharmism’) has been used informally by two of us (JK and LC) and we were both surprised and pleased that another person has used it in an editorial…and to the best of our knowledge, marks 2013 as the year that this word has first been used in a scholarly publication.”

So Dr. Citrome and Dr. Karagianis are clearly pleased with themselves for this lexicological invention, and, presumably, with the verbal chicanery that it entails.  Or perhaps they’re blinded by truthism, a prejudicial aversion to facing facts.

Incidentally, Dr. Citrome’s and Dr. Karagianis’s full definition of pharmaism is given in the IJCP document quoted earlier.  Here it is – read carefully:

Pharmaism, definition

1

: a belief that being associated with a pharmaceutical company is the primary determinant of human traits and capacities regarding scientific discourse and that not being associated with a pharmaceutical company produces an inherent superiority regarding moral and intellectual standing free from bias

2

: prejudice or discrimination

This is doctoral level spin, without a doubt.  They begin with the notion that many people are distrustful of pharma-funded/conducted research.  They convert this distrust, which incidentally is well-deserved, into a prejudice, and – and this is the rabbit in the hat – they give it a name and a definition.  But note how the phenomenon of warranted distrust has morphed into something truly obnoxious by the simple expedient of inventing a word and a definition to go with it.  Warranted and appropriate distrust has now become a belief,

“…that being associated with pharma is the primary determinant of human traits and capacities regards scientific discourse…”

Has anyone on this side of the debate said this, or anything even remotely like this?  What we do say is that pharma influence and money has in the past corrupted a great many psychiatrists, in both academia and clinical practice, and that it is prudent to be cautious and skeptical of pharma-funded research and advertizing.  Note that Drs. Citrome and Karagianis don’t dispute this.  Instead, they create this inane caricature of our position, and critique that, as if it reflected the position on this side of the issue.

And the second part of the definition is even worse:

“…not being associated with a pharmaceutical company produces an inherent superiority regarding moral and intellectual standing free from bias”

Again, has anyone said this, or even suggested it?  Certainly pharma’s deep pockets, and their willingness to spread largesse, has created an environment in which a great many psychiatrists have been corrupted.  But the notion that a lack of contact with pharma will produce the opposite result is simply absurd.

But back to the Psychiatry Advisor article.  Dr. Citrome concedes that:

“Some of the attitudes behind pharmaism have origins in the sins of the past. This includes the deliberate withholding of data, questionable promotional tactics, and rewarding high-volume prescribers. Despite substantial changes in how pharmaceutical companies do business, there is much in the way of lingering suspicion that deceptive practices continue unabated.”

Let’s take a look at that last sentence and the embedded link.  Despite “substantial changes in how pharmaceutical companies do business” there is still suspicion of deception.

I suggest that most people reading this would presume that the “changes” mentioned were of the cleaning-up-one’s-act variety.  And, I further suggest that most people on opening the link would expect to find some account of this clean-up, e.g. publishing the results of all trials, rather than cherry picking those with favorable outcomes, making all relevant data available to outside scrutiny, etc…

But actually, this is not the case.  The link is to a brief article in HealthDay News titled Pharma Sales Reps Finding Access to Physicians Increasingly Difficult (author unnamed).  The gist of the article is that according to a report from ZS Associates, a New York-based marketing consulting firm, there has been a steady decline in drug reps’ access to physicians.  The only changes on the part of pharmaceutical reps mentioned in the article is greater reliance on  “digital communication channels.” Rather than on face-to-face visits, which were the norm in the past.

In particular, there is nothing in the article that might be expected to allay the lingering suspicion concerning pharma-funded research.

So what Dr. Citrome has done is imply that pharma has cleaned house, pretended to provide a supporting reference, and then directed criticism at us pharmaists for retaining – in typically bigoted fashion – our lingering suspicions concerning the integrity of pharma researchers and those psychiatrists who sup at the same table.

And then the Crown Jewel:

“Separating the facts from the rhetoric takes some effort…”

Dr. Citrome, that is, indeed, the case!

He then refers us to “…an excellent summary of the issues…”  This links to an article by Thomas Stossel, MD, et al in the June issue of The International Journal of Clinical Practice, After 20 years, industry critics bury skeptics, despite empirical vacuum.  Dr. Stossel is a professor of clinical medicine at Harvard, and a division director at Brigham and Women’s Hospital.

Here’s the conclusion section of that article, quoted in full:

“As this review reveals, the conflict of interest movement has failed to substantiate its central claim that interactions between physicians, researchers and the medical products industry cause physicians to make clinical decisions which are adverse to the best interests of their patients. After 20 years of impugning the motives of industry and demeaning the professional judgment of physicians, the instigators have failed to produce solid evidence of harm commensurate with their extravagant allegations. At the same time, they have diverted resources away from more worthwhile pursuits, such as basic and applied medical research, clinical care and medical education towards onerous compliance exercises and obtrusive laws and regulations. They have propagated an availability cascade that projects the superficially plausible message that the medical products industry is coopting patient care by corrupting physicians and researchers. Perhaps worst of all, they have made it respectable to ignore the epistemological foundations of medical science, diverting attention away from the scientific merit of the information presented and focusing it instead on the identity and motives of those who present the information.”

A full critique of this article would take us too far afield, but the essential points of the piece are:

  1. The conflict-of-interest (COI) movement has not proven that physician ties to industry have actually harmed patients.
  2. The COI movement has created an environment where information is judged more by the motives of the presenter than by its actual merits.

It’s an interesting, if one-sided, article.  Note  some of the language in the conclusion:

  • the “instigators” [in the COI movement];
  • their “extravagant allegations”;
  • “onerous” compliance “exercises”;
  • “obtrusive” laws and regulations;
  • the “superficially plausible” message.

And the image of the COI movement “diverting attention away from the scientific merit of the information presented” is a far cry from the reality – at least in the psychiatric field –where an eminent researcher at a prestigious university is actually on record as promising a pharmaceutical company a positive result for their drug if they would pony up at least $700,000 for a center on pediatric bipolar disorder at Harvard’s Massachusetts General Hospital.

And incidentally, according to an Editorial in Endocrine Practice, November/December 2009:

“Dr. Stossel is a founder and director of, consultant to, and owns stock options in Critical Biologics Corporation to which his employer, Brigham & Women’s Hospital, has licensed his inventions; he is a director of and owns stock options in Velico Medical Corporation to which Brigham & Women’s Hospital has also licensed his inventions; he currently serves as a consultant to Pfizer.”

But getting back to our psychiatrist, Dr. Citrome, it is clear that he loves the article and he finishes with an upbeat quote:

“Consulting for and collaborating with industry to facilitate the development of new treatments, informing practitioners about new treatments, assisting in conducting clinical trials are all activities that can ultimately benefit patients.”

DISCUSSION

The most notable feature of Dr. Citrome’s article is the fact that it got written at all.  Psychiatry’s corrupt relationship with pharma has been a dominant feature of the profession for the past 40 years.  It is a legacy of the most profound shame and ignominy, which psychiatry made no attempt to correct, until outsiders such as Senator Chuck Grassley, of Iowa, who is probably a pharmaist, began to expose these practices.  Pharma-psychiatry corruption was widespread, and existed in both academia and in clinical practice.  Deliberately tainted pharma research was promoted, not just in professional circles, but also to the general public.  Tawdry pharma adverts in psychiatric journals and in the general media promoted the chemical imbalance lie, and turned dangerous psychiatric drugs into blockbuster products.  For instance, between 1997 and 2007, the number of Americans taking neuroleptic drugs increased from 2.2 million to 3.9 million, bringing the promise of brain shrinkage, tardive dyskinesia, akathisia, and an assortment of other adverse effects to an additional 1.7 million people!  Most of this increase was the result of cooperative psychiatric researchers “discovering” new uses for these products, especially among children and older people.

As in so many areas, psychiatry has no answers to the criticisms it faces. So it resorts to spin; in this case, vilifying the conflict-of-interest movement.

For decades, psychiatry went unchallenged.  Those few of us who drew attention to the spuriousness of its concepts, and the destructiveness of its “treatments” and its corrupt ties to pharma, were marginalized and ridiculed.  We were parodied, and asked if we also believed in witches!

Psychiatry had the backing of pharma dollars, and seemed unassailable.  They neither listened to, nor cared about, voices of dissent.  Theirs was the arrogance of the true believers, and they had the pharmaceutical cash register receipts to prove that they were correct.

Then something happened.  The bubble burst.  The scales fell from the eyes. The Emperor’s nudity was recognized, and psychiatry has no response other than spin. And that’s what we’re seeing in Dr. Citrome’s article:  the COI movement is doing more harm than good!

And, incidentally, at the end of the article, the disclosure states:

“In the past 36 months, Citrome has engaged in collaborative research with, or received consulting or speaking fees, from: Alexza, Alkermes, AstraZeneca, Avanir, Bristol-Myers Squibb, Eli Lilly, Forest, Forum, Genentech, Janssen, Jazz, Lundbeck, Merck, Medivation, Mylan, Novartis, Noven, Otsuka, Pfizer, Reckitt Benckiser, Reviva, Shire, Sunovion, Takeda, Teva and Valeant.”

And just to make my epistemological position clear, I do recognize that a person could have all these ties with pharma and still be objective on these issues.  That’s logic 101.  But I also recognize that there are strong incentives not to bite the hand that feeds us.  That’s psychology 101.  Actually, it isn’t even that.  It’s just common sense.

 

From Hell to Hope

This post was submitted by a reader.   Can.you tell I have a cat just by looking at me?  Can you tell I have a mental illness just by looking at me?

I began to change in my early teens, be it hormones and my shifting brain chemistry, or the stress of my parents seperating. Something stressor from the outside flipped on the switch to a new life filled with major mood swings out of my control.

Low self extreme kept me from meeting or caring about being social. I only went to school because I had to. Luckily one day two high school girls came to my 8th grade health class and talked to us about everything from Stress to Smoking to Sex even Suicide. They asked us to write thrm a question about these topics and others. I wrote “I want to die”It was the first time I admitted to myself or anyone else that I had these thouhts constantly. When class was over the girls kindly asked if I would like to talk to the counselor.

That day was just the beginning of my journey towards understanding mental illness, and ultimately accepting mental Wellness. Over the next few years I spent time in psychiatric hospitals, tried medication that would hopefully be the missing puzzle piece of chemistry my brain needed. Most of the medications tried their best but caused the worst. I never once stopped taking the medication I was prescribed, for I never wanted to feel so completely out of control again. I realized I was accepting my chemical imbalance and each day I began to understand myself and my issues in a much lighter, hopeful way.

The support I recieved on my journey towards wholness helped me acknowledge I was a person not a problem. My mother was my life support at times. She learned all she could about mood disorders and educated our family so as not to judge me, but be very proud. I also met some peers within the mental health community that I still keep in touch with regularly. It was a blessing to know I was not alone in the issues I faced. And that I would be accepted by my peers, for they had experienced similar challenges.

I knew I had a message and a story to tell. I wanted to share my experience From Hell to Hope with students. That is where my journey began. So , with a father whose son has schizophrenia, and I, with my rapid cycling moods we have spoken to over 4,000 high school students since 2006.

My hope is to stop stigma, treating people badly because they seem different. I want to promote education of mental illness so people suffering and their loved ones will believe recovery is real.

Submitted by Antonella Novi

. . . . . . . . . . . . . . . .

Note from Phil:

Obviously this story is not congruent with the central theme of this website:  that mental illness is a spurious, destructive, disempowering, and stigmatizing way to conceptualize human problems.

Readers should be aware that although the author of this story does not declare the affiliation in the above account, a brief Internet search revealed that she has been a volunteer with NAMI for over ten years, and was trained and certified as a state trainer by NAMI in St. Louis in April 2009.

NAMI has been an avid promoter of the spurious chemical imbalance theory for decades.   In it’s 2012 Annual Report (the most recent available), the Corporate and Foundation Sponsors include:  AstraZeneca, Bristol-Meyers Squibb, Eli Lilly & Company, Forest Laboratories, Genentech, GlaxoSmithKline, Janssen, Lundbeck, Merck & Co., Novartis, Otsuka America Pharmaceuticals, Pfizer, Shire, Sunovion, Takeda Pharmaceuticals North America, and Teva.

 

The FDA:  The Fox Guards the Hen House

In their Fall 2013 issue, the Journal of Law, Medicine, and Ethics published a symposium of papers by members of the Harvard’s Edmond J. Safra Center for Ethics.  The symposium was called Institutional Corruption and Pharmaceutical Policy.

The symposium focuses on pharmaceutical products generally, but all the material is relevant and important in the context of psychiatric drugs.

In this post I will highlight one of these papers:  Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs, by Donald W. Light, Joel Lexchin, and Jonathan J. Darrow.

Here are some quotes:

“An extensive range of studies and lawsuits already documents strategies by which pharmaceutical companies hide, ignore, or misrepresent evidence about new drugs; distort the medical literature; and misrepresent products to prescribing physicians…”

“It is our thesis that institutional corruption has occurred at three levels.  First, through large-scale lobbying and political contributions, the pharmaceutical industry has influenced Congress to pass legislation that has compromised the mission of the Food and Drug Administration (FDA).  Second, largely as a result of industry pressure, Congress has underfunded FDA enforcement capacities since 1906, and turning to industry-paid ‘user fees’ since 1992 has biased funding to limit the FDA’s ability to protect the public from serious adverse reactions to drugs that have few offsetting advantages.  Finally, industry has commercialized the role of physicians and undermined their position as independent, trusted advisers to patients.”

“Despite the small number of clinically superior drugs, sales and profits have soared as successful marketing persuades physicians to prescribe the much more costly new products that are at best therapeutically equivalent to established drugs…  Both an American and a Canadian study found that 80 percent of the increase in drug expenditures went to paying for these minor-variation new drugs, not for important advances…  Companies claim that R&D costs are ‘unsustainable.’  But over the past 15 years, revenues have increased six times faster than has investment in R&D.…”

“…allowing companies to test their own products has led them – as rational economic actors – to design trials in ways that minimize detection and reporting of harms and maximize evidence of benefits…”

“…companies have created what can be characterized as the trial-journal pipeline because companies treat trials and journals as marketing vehicles.”

“Furthermore, companies are much less likely to publish negative results, and they have threatened researchers who break the code of secrecy and confidentiality about those results… Positive results are sometimes published twice – or even more often – under different guises.  This further biases meta-analyses – a method of statistically combining the results of multiple studies – and clinical guidelines used for prescribing.  The result is ‘a massive distortion of the clinical evidence… For decades the FDA has kept silent about these practices and about the discrepancies between the data submitted to the FDA by companies and the findings published in journal articles, to the detriment of patients but much to the benefit of the companies.”

The authors offer five suggestions for restoring institutional integrity in this field.

  1. “…while research companies play important roles in discovering and developing superior drugs, they should play no role in testing them.”
  2. “…the FDA needs new leadership to restore public trust and build a new culture focused on safety through enforcement of its existing rules.”
  3. “…user fees must end, and the FDA must be entirely funded by taxpayers-as-consumers. The FDA should be entirely clear about whom it serves.”
  4. “…while approval criteria should allow for a sufficient number of therapeutically equivalent drugs in a class to give clinicians a range of choices…they should also require patient-relevant evidence of superiority.”
  5. “…Congress needs to restore trust by creating a National Drug Safety Board with adequate powers, funds, and mandates to independently investigate and report on drug safety issues.”

This is a meticulously written and well-referenced article.  I urge readers to take a look.  The authors have pulled together all the compelling issues in this matter, and have presented them in a cogent and condensed format.  The article provides excellent material for developing responses to psychiatry’s exaggerated claims, and for lobbying politicians with regards to the obviously much-needed reforms.

According to OpenSecrets.org, the pharmaceutical/health products industry spent $226 million lobbying US politicians in 2013.  By contrast, the defense aerospace industry, popularly regards as a heavy lobbyer, spent $58 million.