"Old Friends" Battle it out Over DSM-V Psychosis

Yesterday, Psychiatric Times published this response to the Allen Frances critique of DSM-V. It is written by William Carpenter, who is Professor of Psychiatry at the University of Maryland, and the chairman of the DSM-V work group on psychosis.

Carpenter begins his response by saying that Allen Frances is an "old friend," although from the tenor of this article, "old" may be the operative word. I know Dr. Carpenter myself, having interviewed him for the March 2007 issue of The Carlat Psychiatry Report, and having chatted with him here and there at APA meetings. He's a southern gentleman, and I found him very forthcoming and honest about a range of issues, including his refreshing skepticism of the value of some of the newer atypical antipsychotics. He has done some consultation with drug companies but very little over the past few years. He's definitely no hired gun, and he speaks his own mind.

The bottom line is that Dr. Carpenter is extremely credible and anything he says or writes you have take seriously. And if you were to boil down his response to Dr. Frances to a few sentences, it would be:

"In actuality, there will be very few substantive changes in the DSM-V. Most of the diagnostic criteria will be the same. We might add a handful of rating scales. There will be no 'paradigm shift.' We are considering adding a sub-threshold psychosis diagnosis but then again we may not--it's a complex scientific issue and we, like you, are concerned about overdiagnosis and stigma."

Basically, Dr. Carpenter is saying that Dr. Frances has created a sensationalized straw man argument, making all kinds of predictions about DSM-V, few of which will materialize.

Of course, Carpenter is focusing on only one of many diagnostic categories, so the Frances critiques may still apply to the rest of DSM-V. Hopefully, we'll hear from the other Work Group chairs soon.

The DSM-V Armageddon, Part 2

Dr. Jane Costello has had enough of DSM-V, and has quit the prestigious DSM-V Work Group on Disorders in Childhood and Adolescence. Her letter of resignation has been making the rounds (with her permission); I've reproduced it below, or you can access it directly here. Dr. Costello is a full Professor at the Duke Institute for Brain Sciences where she co-directs the Center for Developmental Epidemiology, and she is an international expert in understanding the course of mental illness across the life span.

Essentially, Dr. Costello resigned because she feels that the DSM-V process is being rushed to completion without an adequate scientific basis:

"When we began this process [she is referring to the DSM-V work group], we agreed that changes would only be made if there were empirical evidence to support them. Sometimes (as with Charlie’s work on preschool PTSD) this has been the case. But as time has gone by, the gap between what we need to know in order to make revisions and what we do know has grown wider and wider, while the time to fill these gaps is shrinking rapidly. More and more, changes seem to be made for reasons that have little basis in new scientific findings or organized clinical or epidemiological studies."

I encourage you to read her entire letter--it's a fascinating glimpse into the sausage-making process which is how a profession's bible gets constructed.

But wait! There's more!

Dr. Robert Spitzer has sent around this letter written by both himself and Allen Frances to the APA Board of Trustees in which they call for the appointment of a "DSM-V quality control committee" to oversee what they view as a broken process. Their letter recaps some of the same arguments Frances made in this his soon-to-be-published editorial (which I covered in this post) while adding five specific steps that need to be taken.

As William Butler Yeats wrote in his poem The Second Coming, "Things fall apart; the centre cannot hold... " The Fifth Coming of DSM threatens to rend the fabric of American psychiatry. Let's hope some cool heads in the APA's leadership can find a way out of this mess.

Jane Costello Resignation Letter from DSM-V Work Group to Daniel Pine March 27, 2009

Prescription Data-Mining is Getting Battered in Court

Prescription data-mining is a marketing tool in which drug companies purchase information from pharmacies that allow them to spy on doctors' prescribing practices. The companies use this information in a variety of sneaky ways. Front line drug reps download this information to their laptops and use it to tailor their marketing pitches before they call on doctors. Higher level marketing executives use the data to craft targeted marketing campaigns involving everything from pseudo-journals to invitations to promotional dinner meetings.

It is a deceptive and quite nauseating marketing practice, but it has continued through the years because it seemed for a while that everybody stood to win. Drug companies got invaluable demographic information in order to sell the newest and most expensive drugs. Data-mining firms; like IMS, built thier entire lucrative business model on their new identities as information brokers; pharmacies reaped profits by selling prescription info to IMS and their ilk; the American Medical Association profits to the tune of several million per year by whoring out the organization and selling doctors' DEA numbers to data base firms; and finally, individual doctors in their offices started receiving dozens of invitations to fancy dinners by reps who wanted them to prescribe more of their drug.

I've lost count--I think we're up to a "win-win-win-win-win" situation.

But now this corrupt house of cards is tumbling down. Not all at once, but gradually, state by state, appeals court by appeals court.

Here are a couple of recent developments.

1. New Hampshire. In 2006, New Hampshire's legislature banned data-mining. In 2007, lawyers were able to convince a district court to strike down the New Hampshire law by arguing that buying and selling prescription information was protected by free speech safeguards. In 2008, the First Circuit Court of Appeals overturned the district court's decision, and unanimously upheld New Hampshire’s Prescription Confidentiality Act. The forces of greed do not give up easily, and the data-firm lawyers submitted their case to the United States Supreme Court. Well, a few days ago, the Supreme Court declined to consider the case, sending a message to many other states that the ban on data-mining is, in fact, constitutional.

2. Vermont. In 2008, the Vermont legislature passed a law banning prescription data-mining unless physicians specifically opt in to their data being bought and sold. Data firm lawyers descended on the Green Mountain State, and submitted an appeal to the federal Second Circuit Court of Appeals requesting that they grant an injunction blocking the implementation of Vermont's law. Twas not to be. The Appeals courts just refused to block the law.

Other data-mining provisions in other states are being contested by other attorneys, so we will continue to hear more about this issue. But the news is not good for IMS. I hope somebody there is writing out a new business plan.

Psychiatry’s DSM-V Process: Now A Bar Room Brawl

Psychiatry’s diagnostic manual is due for a revision. But what began as a group of top scientists reviewing the research literature has degenerated into a dispute that puts the Hatfield-McCoy feud to shame.

The latest installment in this remarkable episode of American psychiatry involves an editorial by Dr. Allen Frances, the chairman of the committee that created the current version of the the DSM, the DSM-IV. The editorial has not even been officially published (it is in press at Psychiatric Times) but already it has made the rounds of the blogs and is being read and debated widely. Now, the APA has just released this rather stunning response.

Those who are not in psychiatric circles might find their eyes glazing over a bit as they read these articles. But we are witnessing here something dramatic and important. Psychiatry is wrestling with its identity, and in the process is creating the next set of ideas that will guide how real people are diagnosed and treated for years to come. The stakes for everybody are high.

In his editorial, Dr. Frances criticizes the evolving DSM-V on multiple levels, and makes the following claims:

--The process of writing the manual is less transparent and less inclusive than the process he oversaw when he chaired the DSM-IV committee.

--The underlying science of psychiatry has not advanced enough to merit the kind of extreme makeover proposed by the DSM-V chairpeople:

"The simple truth is that descriptive psychiatric diagnosis does not need and cannot support a paradigm shift. There can be no dramatic improvements in psychiatric diagnosis until we make a fundamental leap in our understanding of what causes mental disorders. The incredible recent advances in neuroscience, molecular biology, and brain imaging that have taught us so much about normal brain functioning are still not relevant to the clinical practicalities of everyday psychiatric diagnosis. The clearest evidence supporting this disappointing fact is that not even one biological test is ready for inclusion in the criteria sets for DSM-5."

--The main change being proposed—the official inclusion of a series of rating scales into the diagnostic criteria—is poorly conceived because busy clinicians will reject this extra paper-work.

--Other proposed changes in DSM-V will make it too easy to over-diagnose a range of conditions:

“The result would be a wholesale imperial medicalization of normality that will trivialize mental disorder and lead to a deluge of unneeded medication treatment--a bonanza for the pharmaceutical industry but at a huge cost to the new false positive "patients" caught in the excessively wide DSM-V net. They will pay a high price in side effects, dollars, and stigma, not to mentions the unpredictable impact on insurability, disability, and forensics.”

Frances’ article is compelling, not only because of the substance of his arguments but because of his clear and forceful writing style. With each sentence, you get a sense that this man has carefully thought through all of these issues and is passionately concerned about the future of his field.

The APA’s response, on the other hand, is a weird mixture of bureaucratese and mean-spiritedness. The bureaucratese I can understand—after all, this is a letter crafted by committee. But the nasty tone of the response is astonishing and undignified.

The APA gets off to cringing start by calling Frances and his colleagues liars:

“The commentary “A Warning Sign on the Road to DSM-5: Beware of its Unintended Consequences” by Allen Frances, M.D., submitted to Psychiatric Times contains factual errors and assumptions about the development of DSM-V that cannot go unchallenged. Frances now joins a group of individuals, many involved in development of previous editions of DSM, who repeat the same accusations about DSM-V with disregard for the facts.”

Wow. Can’t grown men have disagreements with one another without resorting to this kind of language? I might have started with something more like, “The commentary “A Warning Sign on the Road to DSM-5: Beware of its Unintended Consequences” by Allen Frances, M.D., is a thought-provoking critique of the DSM-5 process. While we respect and appreciate Dr. Frances’ leadership in American psychiatry over the years, we disagree with several of his points.” (Note to APA--send me all future "defense letters" for editing, at no charge).

After this, there are six paragraphs addressing some of Frances’ specific points. We hear that the DSM-V process has actually been “the most open and inclusive ever” and that the much villified “confidentiality agreement” was created to protect intellectual property rather than to keep proceedings secret. There is a defense of the usefulness of symptom rating scales: “Recent studies underscore the readiness of clinicians in both primary care and specialty mental health settings to adopt dimensional instruments on a routine basis.”

And there is a reasonable reminder of why some changes in the criteria are needed: “Clinicians complain that the current DSM-IV system poorly reflects the clinical realities of their patients. Researchers are skeptical that the existing DSM categories represent a valid basis for scientific investigations, and accumulating evidence supports this skepticism.”

But after a brief, not terribly convincing rebuttal of the merits of Frances' argument, the writers decide to conclude by getting mean and personal again. This time, they accuse Dr. Frances of being deceptive in not disclosing his financial interests in DSM-IV (he is co-author of one book that teaches doctors how to use the manual). Then, they opine that Frances’ real motive in criticizing DSM-V is not a desire to improve diagnosis, but simply greed.

“Both Dr. Frances and Dr. Spitzer have more than a personal “pride of authorship” interest in preserving the DSM-IV and its related case book and study products. Both continue to receive royalties on DSM-IV associated products. The fact that Dr. Frances was informed at the APA Annual Meeting last month that subsequent editions of his DSM-IV associated products would cease when the new edition is finalized, should be considered when evaluating his critique and its timing.”

In other words, Dr. Frances wrote his editorial because he was just informed that once DSM-V is published, the APA will no longer publish new editions of books introducing psychiatrists to the outdated DSM-IV. Somehow, I doubt that this was exactly a news flash to Dr. Frances.

It is disturbing that the APA and DSM leadership would accuse Dr. Frances and his colleagues of being greedy, deceptive, and dumb. Who do they think they are--bloggers?

Team Grassley, a Lawyer's Eye View

You might love him or you might hate him (I'm obviously one of his fans), but either way Senator Charles Grassley and his passionate staff have shaken up the world of medicine and have made "conflict of interest" a household term.

Recently, I read this article published on the website LawyersandSettlements.com that provides a succinct rundown of Team Grassley's accomplishments. Lawyers, of course, are particularly big Grassley fans because each one of his investigations creates instant jobs for dozens of attorneys on various sides of the issue. Thus, you can count on them to be particularly vigilant and accurate monitors of the COI body count as it rises. For the confused, the overwhelmed, or the plain curious, this article makes for a nice fact sheet.

The APA, Power, and the Exclusion of Dissent

Dr. Doug Bremner has a fascinating but unsettling post about colleagues disinviting him to co-author an academic paper, because they were upset by this blog post he had written.

I have no idea how deep this issue goes, and there is always more to everything than meets the eye, but I do have my own recent personal experience of being shunned by the academic establishment, and I thought this would be an opportune time to tell that story.

As some of you know, in 2008 I was elected by those liberal Massachusetts psychiatrists to be one of four state representatives to the American Psychiatric Association. This means that I attend monthly meetings of the council of the Massachusetts Psychiatric Society, as well as quarterly meetings of the New England region (called “Area 1”) of the APA.

One of the things that happens when you get into a leadership position in a big organization is that you find out that there are dozens of committees and task forces and this is where all the real work takes place. Sometimes you get appointed by a powerful person, like former president Nada Stotland, who appointed me to a couple of committees, one of which was the task force leading to the APA’s decision to phase out industry supported CME at the annual meeting. Other times, you end up in committees via informal protocol.

Thus, for example, if you are on one of the APA Area councils (which I am), you may be invited to serve as an “Area council liaison” to a given committee. One of these committees is the “APA Steering Committee on Practice Guidelines.” As you can see here, this committee is composed of about 24 people, seven of whom are liaisons from each of the seven Areas of the APA. It’s an important committee, because it is in charge of reviewing and approving any new practice guidelines. The practice guidelines then filter their way out into the community of mental health professionals and influence how patients are treated.

Recently, my Canadian colleague Joseph Berger announced that at some point over the next year, he would be replaced on the Area 1 committee by one of his colleague, and that therefore his slot on the Practice Guidelines Committee would be open. I expressed an interest in it, because sifting through practice guidelines and the research upon which they are based is basically what I do for a living as the editor of The Carlat Psychiatry Report. Dr. Berger was happy to find an eager volunteer, and he graciously made some email introductions to the various players involved.

Here’s where things began to go sour. I heard through this or that grapevine that some of the practice guidelines committee members were concerned about my “conflicts of interest.” I was surprised, since a recent study had found that 90% of members of three major work groups of the committee had conflicts of interests (COIs) with pharmaceutical companies.

Obviously, COIs per se are not forbidden. But perhaps I represented a special case, because, while I have no drug industry relationships, I publish what might be considered a competing publication. Perhaps they were concerned that I would spy on their process to improve The Carlat Psychiatry Report.

But I found out that the concern was about something else entirely. Somebody on the committee said that I had embarrassed members of the DSM-V committee by publishing something on my blog. I wracked my brain for what this could be. Finally, while on my morning jog, it came to me.

Back in October of 2008, I posted this article reviewing the breaking news about the extent of Dr. Charles Nemeroff’s undisclosed conflicts of interest at Emory. There were almost 30 comments on that posting, and one of the commenters, who was anonymous, left the following comment:

“A reminder that a further feature of pseudoacademic pseudopsychiatry is that the group noted by Dr. Gitlow defines the diagnoses we use, and defines them of course in a way that not only maximizes drug treatment, but shapes them according to the interests of particular drug corporations. One recent example only: Dr. Schatzberg has been campaigning at the APA DSM V committee meetings to dilute the criteria for major depression with psychotic features, so that the drug his company manufactures for the condition might attain broader use.
October 5, 2008 8:17 PM”

I confess that I don’t scrutinize every single one of the comments that are left on my blog. I publish just about any comment that comes in, as long as it is not profane or completely off-topic, and I make no guarantee that comments are accurate. I also often disagree vehemently with commenters. That’s called healthy debate.

At any rate, somebody in the higher APA echelons saw this comment, and I was told that it inaccurate, and that my publishing it reflected poorly on both myself and on the APA.
While under no legal obligation to do so, in order to soothe hurt feelings, I decided to delete the comment, and announced the fact in this post.

Well, no good deed goes unpunished, and somebody on the practice guidelines committee is still sore about the incident and believes this shows I am a loose cannon and that my presence would inhibit free discussion on the guidelines committee.

Actualy, if anything, I would think that the presence of someone who has been at the forefront of ethics reform efforts would help to legitimize and improve the APA guidelines process.

The episode is profoundly disappointing to me personally, because I have a particular interest in making the currently dry guidelines more readable and therefore more likely to be read by practicing psychiatrists.

But it is also disappointing to me as a member of the APA, because I would have thought that the tent of the organization is big enough to tolerate the rubbing of shoulders between people who may disagree strongly on some topics. Psychiatrists, of all professionals, should know that avoiding confrontation is rarely the road toward health, whether psychological or organizational.

Geodon Ineffective for Bipolar Depression; or, Watch ClinicalTrials.gov in Action!

According to results recently posted by Pfizer on ClinicalTrials.gov, the antipsychotic Geodon is not effective for the treatment of depression in patients with bipolar disorder.

Atypical antipsychotics, like Geodon, are all FDA-approved for the manic phase of bipolar disorder, but only Seroquel is approved for treating bipolar depression, though just how effective it is remains controversial.

The Geodon results are noteworthy because the only reason we even know about them is that drug companies are now required to post the results of clinical trials on the clinical trials registry. This was a requirement of the FDA Amendments Act of 2007; before this act, companies could voluntarily post the protocol of a research study on the registry, but it was not compulsory and there was no requirement that they ever publish the results. The FDAAA, among other things, both make it mandatory for companies to post new trials on the registry, and, even more significantly, required that they actually post the results of those trials. This latter requirement did not kick in until September of 2008.

In the past, companies have simply buried research results if they showed that their drugs were ineffective. For example, Erick Turner and his colleagues published this paper in the New England Journal of Medicine showing that drug companies had selectively published only the positive findings regarding antidepressant drugs. Specifically, companies had published 94% of all their positive studies of antidepressants, but only 38% of their negative studies; furthermore, even most of the published “negative” studies had been spun so that once in print they appeared to be far more positive than they were.

From the standpoint of a psychiatrist trying to figure out which drugs work, the bottom line was this: if I relied on the published medical literature for information (and what else can I rely on?), it would seem as though 94% of all antidepressant trials are positive. But if I had access to the suppressed data as well, the true figure is that only about half--51%--of trials are positive.

To come back to Geodon, before FDAAA, Pfizer would presumably have either not published the results of the recent bipolar depression studies, or would have published them as falsely positive. Doctors would have continued to prescribe the drug in this condition under the false assumption that if one atypical antipsychotic is effective (Seroquel), then they must all be effective.

Here is a very brief run-down of the two studies, both of which were placebo-controlled, double blind, multi-site trials of patients with bipolar disorder I who were depressed when they entered the studies. One of them, identified as study NCT00282464, was a 6-week flexible dose study comparing Geodon with placebo, and the other one, NCT00141271 was a fixed dose trial comparing both high and low dose Geodon with placebo.

The studies were complex, with many different outcome variables assessed, but the bottom line is that neither of them managed to show that Geodon was significantly more effective than placebo on the primary depression rating scales. Will the results be spun in various ways to make them look good? You betcha. We will undoubtedly see publications coming out of this data that will emphasize certain outcome scales, at certain time-points, in certain kinds of patients, etc…. The data will be tweaked to nth degree.

But at least we now have a law on the books requiring companies to post the data for all to see, so that we may judge for ourselves whether published papers are accurate renditions of the data. For that, we should be grateful to both Congress and to former President Bush, who signed the legislation into law.