09/1/17

Circle the Pfizer Wagons

© Darin Burks | 123rf.com

The U.S. Preventive Services Task Force (USPSTF) recommended that all adults, including pregnant women and women who have recently given birth, be screened in primary care settings for depression. The screening would be done by: general practitioners, family physicians, nurse practitioners or physician assistants. USPSTF said screening adults for depression in primary care settings was accurate, it was effective in relieving depressive symptoms and the likelihood of harm from screening and treatment was small. The problem is that over 60% of individuals diagnosed with depression in primary care did not meet the DSM criteria for major depressive disorder. This rises to 80% with individuals over 65.

Albert Siu and the USPSTF published “Screening for Depression in Adults” in the January 2016 issue of JAMA. The authors said: “The USPSTF found convincing evidence that treatment of adults and older adults with depression identified through screening in primary care settings with antidepressants, psychotherapy, or both decreases clinical morbidity.” Commonly used screening instruments included the Patient Health Questionnaire (PHQ) in its various forms, as well as several others. But the USPSTF did not believe these instruments were getting as many false positives as noted above. “The accuracy of screening tests in the general adult population was established in the 2002 and 2009 USPSTF reviews and found to be convincing.”

Psychiatrist Vivek Datta pointed out the USPSTF guidelines did recommend that screening occurred when there were “adequate systems in place” for further evaluation and treatment. However, “55% of all US counties do not have a single mental health provider.” He noted that many of the symptoms screened for are nebulous and include “symptoms that are quite common in the general population and do not necessarily indicate a mental disorder requiring treatment.” They could represent the effects of a chronic medical problem. Moods are influenced by a variety of factors, such as our level of physical activity, what we eat, our financial security, alcohol and drug use, to name a few.

Symptoms of depression can occur as a result of lifestyle factors, substance use, medical illness, life events, interpersonal difficulties, and as a consequence of wider social policies. Comprehensive assessment frequently does not occur because of the lack of adequate services for those with mental health problems. The recommendation to screen all adults for depression ignores the social matrix in which depression occurs, will lead to further overdiagnosis and overtreatment of minor morbid mental states, and further overburden mental health services.

A Glut of Antidepressants” was published on August 12, 2013, in The New York Times. It mentioned an April 2013 study published in the journal Psychotherapy and Psychosomatics that found almost 62% of 5,639 individuals “who had been given a diagnosis of depression within the previous 12 months did not meet the criteria for major depressive episode.” Several other studies have reported that: “diagnostic accuracy is low in general practice offices.” The study’s lead author said: “The vast majority of individuals diagnosed with depression, rightly or wrongly, were given medication.” Doctors must resist the temptation “to take out the prescription pad and write down an antidepressant and hand it to the patient.”

The NYT article did indicate that not only are doctors prescribing more medication, their patients are demanding it more. I think this is a likely an outcome of the decision to permit direct-to-the-consumer advertising for pharmaceuticals in 1997. See “Pharma and Advertising” or “Not Everything is As It Appears” for more on this topic. If anything at all was done to “confirm” the patient’s or doctor’s impression that there was a depressed mood state, using a quick screening instrument seems likely given the short time period most patients spend with medical staff in a primary care setting.

James Davies, the co-founder of the Council for Evidence-Based Psychiatry, wrote “The Sedated Society,” where he commented on how a BBC radio program had failed to mention the problem with the PHQ-9 (mentioned above) and the GAD-7, which he said two of the most powerful questionnaires in the NHS (National Health Service). He said they have been used throughout the primary care system in the UK to assess whether or not a person has depression or anxiety. He said: “They set a very low bar for what constitutes having a form of depression or anxiety for which a drug should be prescribed.” He said the tens of millions of people who filled out these screening questionnaires don’t know that Pfizer Pharmaceuticals paid for their development and continues to hold the copyright for them. Their distribution throughout the NHS was paid for by Pfizer, which incidentally makes two of the most prescribed antidepressant and anti-anxiety drugs in the UK.

Although the BBC didn’t get Davies’s message out about the PHQ-9 and GAD-7, several news outlets did. At Vice, Hannah Ewens said “a few of us in the office” took the test, with everyone except one person got at least a score of mild depression. She personally scored within the “moderately severe depression” range, but doesn’t have depression at the moment. “If I have trouble sleeping ‘on several days’ or ‘nearly every day’ that bumps up my score significantly. And herein lies the problem: all of the indicators are symptoms of a modern lifestyle as well as signals of depression.” Ewens added that James Davies believes reliance on these questionnaires is becoming too commonplace because GPs don’t have the time to do proper interviews.

The Telegraph, another UK media outlet, echoed the Davies concern that the threshold for identifying possible depression was too low. Henry Bodkin noted that a PHQ chart was likely present in almost every GP consulting room over the last 20 years. He also said critics like Davies have said the GAD-7, also developed by Pfizer to screen for anxiety, sets the diagnosis bar too low. “These forms have a very low criteria for anxiety and depression. . . . Millions of people have filled them in and got medication, but did they know they were developed by Pfizer?”

Pfizer enlisted two “rock stars” in the field of psychiatric diagnosis to develop the PHQ-9 and GAD-7: Robert Spitzer and Janet Williams. Spitzer was the chairperson for the seminal changes incorporated into the DSM-III. Originally Williams was his text editor; later she became his wife and collaborator. Listen to an All Things Considered broadcast on Spitzer and the DSM, “The Man Behind Psychiatry’s Diagnostic Manual.”

In the September of 2001 issue of the Journal of General Internal Medicine, Kurt Kroenke, Robert Spitzer and Janet Williams published “The PHQ-9.” Their article examined “the validity of a brief, new measure of depression severity” called the PHQ-9. They concluded that data from their two studies provided “strong evidence for the validity of the PHQ-9 as a brief measure of depression severity.” Kroneke et al. also said brief measures were more likely to be used in the busy setting the typical medical practice. The brevity of the PHQ-9 was thought to make it “an attractive, dual-purpose instrument for making diagnoses and assessing severity of depressive disorders.” The Acknowledgements section said the development of the PHQ-9 was underwritten by an educational grant from Pfizer US Pharmaceuticals. Scrolling down further you’ll see:

From the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PRIME-MD PHQ). The PHQ was developed by Drs. Robert L. Spitzer, Janet BW Williams, Kurt Kroenke, and colleagues. . . . PRIME-MD is a trademark of Pfizer Inc. Copyright 1999 Pfizer Inc.

Then in the May 2006 issue of JAMA Internal Medicine, the same three authors introduced the GAD-7, a brief self-report scale to identify generalized anxiety disorder (GAD). Not surprisingly, they concluded: “The GAD-7 is a valid and effective tool for screening for GAD and assessing its severity in clinical practice and research.” They expected the GAD-7 to have “considerable utility in busy mental health settings and clinical research.” Once again is an acknowledgement that the development of the GAD-7 was underwritten by an unrestricted educational grant from Pfizer Inc.

If you want to see or use copies of these scales, Pfizer’s lawyers have been clearly involved in dialing back the company’s responsibilities if the scales don’t live up to their creator’s optimistic expectations. On the Pfizer website, on the “Terms of Use” page for the two scales, is the following. Pfizer said since the questionnaires relied on patient self-report, all responses should be verified by the clinician. A definitive diagnosis should be made on clinical grounds, “taking into account how well the patient understood the questionnaire, as well as other relevant information from the patient.” Diagnoses should rule out normal bereavement, Bipolar Disorder, and other potential causes of depressive symptoms. Then there is the following disclaimer. The “all caps” formatting is in the original.

PFIZER MAKES NO WARRANTIES OR REPRESENTATIONS OF ANY KIND AS TO THE ACCURACY, CURRENCY, OR COMPLETENESS OF THE INFORMATION ACCESSED AND USED THROUGH THIS WEB SITE.
YOU AGREE THAT ACCESS TO AND USE OF THE PHQ AND GAD-7 SCREENERS IS AT YOUR OWN RISK. PFIZER DISCLAIMS ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. NEITHER PFIZER NOR ANY PARTY INVOLVED IN CREATING, PRODUCING, OR DELIVERING THE PHQ/GAD-7 SHALL BE LIABLE FOR ANY DAMAGES, INCLUDING WITHOUT LIMITATION, DIRECT, INCIDENTAL, CONSEQUENTIAL, INDIRECT, OR PUNITIVE DAMAGES, ARISING OUT OF ACCESS TO, USE OF OR INABILITY TO USE THE PHQ/GAD-7, OR ANY ERRORS OR OMISSIONS IN THE CONTENT THEREOF.

The rhetoric about the GAD-7 and PHQ-9 and its variations related by their creators, Spitzer, Williamson and Kroneke seems to have been negated by Pfizer. Instead of the PHQ-9 being “an attractive, dual-purpose instrument for making diagnoses and assessing severity of depressive disorders” and the GAD-7 being “a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research,” Pfizer disclaimed all warranties expressed or implied for a particular purpose. Pfizer nor any party involved in creating the PHQ/GAD-7 will be liable for any damages from access or use of these questionnaires. Any users access and use the PHQ and GAD-7 does so “at your own risk.”

It seems that Pfizer circled their wagons to avoid any corporate liability coming from the use of these questionnaires despite the fact they paid for their development and continue to market them aggressively to general practitioners in the US and the UK. But the potential for the over diagnosis and over treatment of depression through the PHQ-9 has now reached a new height. Psychiatry Advisor reported in August of 2017 that Google announced whenever someone searches for ‘clinical depression,’ they have an option to take the PHQ-9. Google partnered with NAMI, the National Alliance on Mental Illness, to make depression screening with the PHQ-9 part of searching for ‘depression’ on the site. NAMI said: “We hope that by making this information available on Google, more people will become aware of depression and seek treatment to recover and improve their quality of life.”

So where did all that effort with the PHQ-9 and GAD-7 get Pfizer? Pfizer currently hold the rights to the brand rights for Xanax (alprazolam), an anti-anxiety drug, and Zoloft (sertraline), an antidepressant. Both have been available as generics for a number of years. And although The Telegraph article didn’t name Pfizer’s top selling antidepressant and anti-anxiety drugs in the UK, they must be the same two. Up-to-date yearly sales data for psychiatric drugs is hard to come by, unless you pay an organization like IMS for access to their sales data. But there is data available from 2013.

IMS Health listed the top 25 dispensed prescriptions in the US in 2013. Xanax and its generic, alprazolam, was the 13th most prescribed medication. Zoloft and its generic, sertraline, was the 18th most prescribed medication. Among the psychotropic medications listed they were number one and number three respectively. PsychCentral reported similar findings, with the added information that Xanax was the number one prescribed psychiatric drug in 2005, 2009, 2011 and 2013. Zoloft sank as low as the 4th most prescribed psychiatric drug in 2009 and the 3rd most in 2011.

10/7/15

Psychiatry, Diagnose Thyself! Part 2

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© lightwise | 123rf.com

Similar to what happened to Robert Spitzer, just as Jeffrey Lieberman released his “untold story of psychiatry” in Shrinks and began his book tour, the very themes he presented as the uncensored truth about psychiatry were being challenged by others. Whose story about psychiatry and its history would the public believe? Although Lieberman did acknowledge in his CBC interview that he was “unfortunately” familiar with Robert Whitaker, he didn’t elaborate on how far back their acquaintance goes.

Like his description of David Rosenhan in Shrinks, Lieberman attempted to discredit what Whitaker and T. M. Luhrmann had to say by his ad hominem assessment of them (see “Psychiatry, Diagnose Thyself! Part 1”). Luhrmann’s work on psychiatry, Of Two Minds, received several awards, including the Victor Turner Prize for Ethnographic Writing and the Boyer Prize for Psychological Anthropology. Anatomy of an Epidemic by Whitaker won the 2010 Investigative Reporters and Editors book award for best investigative journalism. And in 1998, he co-wrote a series on psychiatric research for the Boston Globe that was a finalist for the Pulitzer Prize for Public Service. It was while writing this series of articles that Lieberman and Whitaker first became acquainted with each other.

The first installment of the series, “Testing Takes Human Toll” was published on November 15, 1998. In this article, Whitaker and others described how beginning in 1972, psychiatric researchers used a variety of agents such as methylphenidate (Ritalin, Concerta), ketamine, and tetrahydrocannabinol (THC) “to deliberately provoke psychotic symptoms in more than 1,200 schizophrenic patients.” In some cases, the level of psychosis experienced by these patients was called “severe.” Jeffrey Lieberman was one of those researchers. He conducted methylphenidate challenge tests for more than a decade.

Here is a sampling of three articles where Lieberman was a co-author of studies where methylphenidate was given to schizophrenic patients in order to activate psychotic symptoms.

In a 1987 study, 34 stable outpatients receiving neuroleptic treatment were given an infusion of methylphenidate and then withdrawn from their neuroleptic medication. Three weeks after they were withdrawn from their psych meds, they were given another infusion of methylphenidate. Then the unmedicated patients were followed up for 52 weeks—or until they relapsed; in other words their symptoms returned.

A 1994 study had a similar methodology, 41 stable patients receiving neuroleptic treatment were given an infusion of methylphenidate. They were also withdrawn from their neuroleptic meds and followed for 52 weeks, or until relapse.

In a 1990 study, 38 patients who met the criteria for schizophrenia or schizoaffective disorder were given an infusion of methylphenidate, followed by a regimen of standard acute neuroleptic treatment. This time the patients were individuals who were experiencing their first acute episode of psychosis. The methylphenidate produced an increase in psychopathology reflected by a worsening of their symptoms.

Another 1987 article with Lieberman as a co-author was a meta-analysis of 36 studies that used psychostimulants (PS) in schizophrenia. The authors noted that non-amphetamine drugs like methylphenidate appeared to have a greater “psychotogenic potency.” In other words, they elicited a greater psychotic reaction than amphetamine drugs. “Approximately 40% evidence a psychotogenic response to PS administration in doses that are subpsychotogenic in normal’s.” Don’t miss the fact that Lieberman knowingly used a psychostimulant in his own studies that he knew would elicit a greater, more intense psychotic reaction than amphetamine drugs.

Psychologist Bruce Levine gave a scathing response to Lieberman’s “menace to society” remark concerning Whitaker. He unpacked the pre-1994 studies and questioned the claim that the subject and family members were willing and able to sign informed consent. Levine said: “Who in their right mind would give consent for themselves or for a family member for a procedure that was hypothesized to make a patient worse?”

When Whitaker interviewed Lieberman for the first article in the Boston Globe series, “Testing takes human toll,” Lieberman admitted that the induced symptoms were sometimes “scary and unpleasant.” He even acknowledged that some patients get worse. “But in my experience, the symptoms never exceeded the range of severity that occurred in the course of their illness previously.” Ironically, Lieberman was entirely silent on the topic of schizophrenic challenge studies in Shrinks. They weren’t even discussed as one of the positive examples of how modern psychiatry “now practices an enlightened and effective medicine of mental health.”

Dr. Davis Shore, who was doing ketamine challenge studies for the NIMH, minimized the harm done to patients in challenge studies.  He argued that the increase in symptoms was very short-lived in patients who had experienced them over years. ‘”To say that increasing a particular symptom – like hearing voices for a couple of hours in somebody who has been hearing voices for 10 years – is causing [suffering] rather seems like a stretch.” Here is a 1987 account of one such “stretch” Whitaker saw reported in the scientific literature. The individual was a patient with bipolar disorder who was injected with methylphenidate.

Within a few minutes after the infusion, Mr. A experienced nausea and motor agitation. Soon thereafter he began thrashing about uncontrollably and appeared to be very angry, displaying facial grimacing, grunting and shouting … 15 minutes after the infusion, he shouted, ‘It’s coming at me again, like getting out of control. It’s stronger than I am.’ He slammed his fists into the bed and table and implored us not to touch him, warning that he might become assaultive. Gradually over the next half hour, Mr. A calmed down and began to talk about his experience.

Whitaker’s 1998 series for the Boston Globe is still a worthwhile read. Part 2, written by Deborah Kong, gives more details on “Debatable forms of consent.” She noted how researchers have conceded in court documents that they did not tell mentally ill patients the whole truth for fear of scaring them away from enrolling in the experiments. Part 3 by Robert Whitaker, Lures of riches fuels testing, looks at the influence of the pharmaceutical industry on drug research. In Part 4, “Still no solution in the struggle on safeguards,” Dolores Kong wrote about how the psychiatric community has argued that challenge and washout studies are important avenues to understanding the underlying biology of mental illness. “To this day, some psychiatric specialists are conducting medical experiments in which research subjects are allowed to grow sicker.”

On May 6, 2015, Robert Huber received a letter of apology from the University of Minnesota saying that the university was sorry that his “rights and welfare were compromised.” In July of 2007, Huber was admitted to the University of Minnesota Medical Center with symptoms of schizophrenia, where he was for two weeks. During that time, he was recruited daily to volunteer for a drug trial for an experimental drug called bifeprunox. He was repeatedly told the drug was safe, even though determining safety was one of the goals of the study. In the process of his recruitment for the study, he was also shown “the cost of his hospital care if he didn’t sign up and have the study pick up the tab.”

But there were problems. He experienced severe abdominal pains, which required two ER visits. His records indicated that the doctor in charge of the study thought it unlikely that they were due to the medication. At one point, he contemplated suicide because of the pain. In August of 2007, the FDA decided to not approve bifeprunox, but Huber was not informed of that decision and remained in the study until he withdrew in October of 2007. The university also acknowledged that he was not informed in his consent form of the risks of a medication washout that was necessary before starting the new medication, bifeprunox.

There are several concerns with these kinds of psychiatric research methods. The giving and withholding of medication may create unique risks for the subject. Individuals diagnosed with schizophrenia are at a greater risk of suicide during relapses. Adverse events of all types are more likely to occur as medications are increased or decreased in dosage. George Annas, chair of Health Law Department at Boston University School of Public Health said: “We let researchers do things to people with mental illness that we would never let them do to people with physical illness.”

There are three basic research designs with medications in psychiatry: placebo, washout (where medication is tapered and withdrawn), and challenge (symptoms are provoked in some way). In “Ethics in Psychiatric Research: Study Design Issues,” Gordon DuVal gave a helpful summary of these three research designs. His conclusion was:

Despite a history that has included serious abuses, psychiatric research is important—not least to those who suffer from mental illness. Clinical psychiatric research creates challenging ethical dilemmas. The choice of research design can have significant implications for subject safety and must be carefully considered. While these issues are not necessarily unique to this context, the particular vulnerabilities attending psychiatric illness merit close attention in the design of research involving persons with psychiatric disorders.

DuVal singled out challenge studies as particularly risky, despite the potential research benefits. The risk is that someone who is already sick or vulnerable to a negative response to the challenge “may have harmful symptoms provoked or exacerbated or may suffer a relapse.” He said it was unclear whether the balance of risks and potential benefits can ever justify people in studies where “potentially harmful responses are intentionally induced.” But this is exactly what schizophrenic challenge studies done by Lieberman and others were designed to do. They often have a washout element, which heightens the ethical concerns. “Finally, for practical reasons, challenge studies often require that subjects be deceived, or at best partially informed, about the details of the study.”

A search in Google Scholar found 1,030 entries for “challenge studies”, psychiatry since 2011. This suggests that some psychiatric specialists are still conducting medical experiments in which individuals with various mental illnesses are allowed to grow sicker, and even triggered to so do, in the name of science. This technique is seen as a valuable and necessary element in psychopharmacological research. D. C. D’Souza and J. H. Krystal said in 2001 that: “Psychopharmacological challenge studies have made significant contributions to understanding the neurobiological basis of psychiatric disorders.” They may continue to provide an important method of testing pathophysiologic mechanisms and studying potential pharmacotherapies.

So here’s what I’m thinking. Dr. Jeffery Lieberman writes a book that is supposed to be the untold story of psychiatry for the general public. But he is totally silent in Shrinks about research where psychiatric symptoms are triggered in patients by challenge agents. It’s not given as an example of the scientific standing of the field or the revolutionary process in psychiatry over the past fifty years. His past use of the methods, coupled with his silence, also suggests he still believes that it has a place in psychiatric research. And it certainly is not given as an example of psychiatry’s “long sojourn in the scientific wilderness” in Shrinks along with lobotomies, coma therapy, and fever cures.

Could he have decided to not mention challenge studies, because he thought the public would not accept them or would misunderstand their importance? Worse still, similar to the Rosenhan study, would they be seen as an example of the bankruptcy of psychiatry? Robert Whitaker could connect the dots for the general public between Lieberman and his past challenge studies, so did he become a particular target for marginalization and discrediting by Lieberman? Another possibility is that discussing challenge studies complicates the story of progress and heroism Lieberman wanted to tell in Shrinks. His goal does seem to have been a retelling of the same old rhetoric put forth by the APA since 1980. As Whitaker observed in his review of Shrinks, this mantra was:

The disorders in the DSM are real diseases of the brain; the drugs prescribed for them are quite safe and highly effective; and psychiatric researchers are making great advances in discovering the biology of mental disorders. Therapeutic and research progress are to be found at every turn.

It will be interesting to see what the future holds for psychiatry. Does the given rhetoric of the APA hold sway, or will the growing questions about psychiatry and diagnosis lead to another revolutionary change. Will the public continue to believe Lieberman’s version of the untold story of psychiatry; or will they begin to see it in light of what Whitaker has written? Stay tuned.

09/16/15

The Quest for Psychiatric Dragons, Part 2

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© Olesia Sarycheva |123rf.com

The fallout from the Rosenhan study couldn’t have come at a worse time for psychiatry. Spitzer was in the midst of trying to put out one fire with the crisis brought about by gay activism against the APA. Then Rosenhan demonstrated that “psychiatrists could not distinguish the sane from the insane” from another angle.

Pseudopatients were admitted into psychiatric hospitals, but were not identified as such by hospital staff. The problem with the unreliability of psychiatric diagnosis was now front-page news, just as Spitzer and one of the coauthors of his 1967 article on the kappa statistic, Joseph Fleiss, were about to publish their own critique of psychiatric diagnosis. Their study, “A Reanalysis of the Reliability of Psychiatric Diagnosis,” became another classic article in the psychiatric literature.

The Spitzer and Fleiss study was received by the British Journal of Psychiatry on January 17, 1974, and published in the October 1974 issue of the BJP. The Spitzer and Fleiss article was received by the BJP about a month after the APA decision to remove homosexuality from the DSM-II and a year after the Rosenhan study was published.

Applying the kappa statistic in the re-analysis of five previous studies of diagnostic reliability, Spitzer and Fleiss said: “The reliability of psychiatric diagnosis as it has been practiced since at least the late 1950s is not good.” They were confident that developing structured interviews and specifying all diagnostic criteria “will result not only in improved reliability, but in improved validity, which is, after all our ultimate goal.” In The Selling of DSM, Stuart Kirk and Herb Kutchins said: “This article carefully and dramatically sets the stage for DSM-III. It reinterprets and denigrates the past, refers to innovations being currently developed by the authors and others, and predicts success in the future.”

The historical context suggests to me that the one-two punch of the gay activists and the Rosenhan study caught Spitzer and the other psychiatric researchers by surprise. These two events not only raised questions about the unreliability of psychiatric diagnosis, but they did it in a way that was easy to grasp by the public. They also publicly embarrassed psychiatry. How could trained psychiatrists not be able to tell whether someone was faking their symptoms? How could homosexuality be voted out of being a mental disorder? What implications do these two events have for diagnosing other so-called mental disorders?

Psychiatry now faced serious threats to its credibility, perhaps to its very existence. As Whitaker and Cosgrove noted in Psychiatry Under the Influence, the APA did recognize how the rampant criticism threatened their profession. “The public did not have a ‘strong conception of psychiatry as a medical specialty,’ and failed ‘to recognize a psychiatrist’s special competence in mental health care.’”

After his achievements in removing homosexuality from the DSM-II, and being appointed the chair for the DSM-III, Spitzer took on Rosenhan. Spitzer published his critique of Rosenhan’s study in the Journal of Abnormal Psychiatry in October of 1975, “On Pseudoscience in Science, Logic in Remission, and Psychiatric Diagnosis.” Spitzer’s article was originally received on November 1, 1974, less than a month after he and Fleiss published their article. He revised and resubmitted it on April 14, 1975. Several other articles on Rosenhan’s study were published in the same issue of the Journal of Abnormal Psychiatry. Spitzer now defended psychiatry and to a certain extent, diagnosis. Kirk and Kutchins noted that Spitzer was in the awkward position of defending psychiatric diagnosis, while he was in the process of restructuring it.

His rhetoric was clever and forceful. He characterized Rosenhan’s study as “pseudoscience,” playing to Rosenhan’s reference to his “pseudopatients.” Spitzer also referred to Rosenhan’s discussion of the pseudopatients discharge diagnosis as schizophrenia in remission as “logic in remission.” Kirk and Kutchins said:

Some of Spitzer’s criticisms of the design of the study were warranted, although his zeal to discredit Rosenhan sometimes led him simply to disregard or distort basic observations. . . . The importance of Spitzer’s comments are not what they tell us about Rosenhan’s study, but what they tell us about Spitzer’s new enterprise, the making of the DSM-III.

First he sought to invalidate Rosenhan’s basic point, namely the criticism of psychiatric practices that could not distinguish the sane from the insane. According to Spitzer, “A correct interpretation of [Rosenhan’s] own data contradicts his own conclusions. In the setting of a psychiatric hospital psychiatrists are remarkably able to distinguish the ‘sane’ from the ‘insane.’” Secondly, he used his article to redefine the problem of psychiatric diagnosis as one of reliability, and cited his own article, “A Reanalysis of the Reliability of Psychiatric Diagnosis,” and its recommendations in support of this conclusion. “Recognition of the serious problems of the reliability of psychiatric diagnosis has resulted in a new approach to psychiatric diagnosis.” In effect, Spitzer was saying to his audience of psychiatrists and other mental health professionals, “We already knew about the problem and have been working on a solution.”

Spitzer then reworked his article and published the revision in the Archives of General Psychiatry: “More on Pseudoscience in Science and the Case for Psychiatric Diagnosis.” The article was accepted for publication on December 12, 1975 and published in the April 1976 issue. In the introductory comments of his 1976 article, Spitzer observed that partly because of the prestige of Science, the journal in which it was published, and partly because it said what many others wanted to hear, “The [Rosenhan] study was widely acclaimed in the popular news media. . . . As a consequence, this single study is probably better known to the lay public than any other study in the area of psychiatry in the last decade.” And he was right.

In February of 1980, as the DSM-III was about to be published, Spitzer et al. published an article in The American Journal of Psychiatry that reviewed the achievements and changes in psychiatric diagnosis within the DSM-III. They also claimed the reliability problem had been significantly improved. “For most of the diagnostic classes the reliability was quite good, and in general it was much higher than that previously achieved with DSM I and DSM II.” As it turned, out this was not true. In their book, The Selling of DSM, and in an article, “The Myth of the Reliability of DSM,” Stuart Kirk and Herb Kutchins demonstrated how the standards for interpreting reliability were dramatically shifted in order to make it easier “to claim success with DSM-III, when in fact, the data were equivocal.”

David Rosenhan died on February 6, 2012 after a long illness. His obituary published in American Psychologist commented: “The lessons he cared most about offering, in the classroom as in his research, were about human dignity and the need to confront abuse of power and human frailties.” Robert Spitzer retired in December of 2010. According to Jeffrey Lieberman in Shrinks, it was because of a severe and debilitating form of Parkinson’s disease. But the fight over the legitimacy over psychiatric diagnosis continues and Robert Spitzer has been one of the critics of the recent revision process for the DSM-5. Joining him in this dispute is Allen Frances, the chair of the DSM-IV Task Force.

Writing for Wired, Gary Greenberg noted that the DSM-5 battle comes at a time when the authority of psychiatry “seems more tenuous than ever.” The director of the National Institute of Mental Health (NIMH), Thomas Insel, announced the NIMH wouldn’t be using the DSM to structure its research. “Some mental health researchers are convinced that the DSM might soon be completely revolutionized or even rendered obsolete.” Other psychiatrists privately fret that “the DSM-5 will create ‘monumental screwups’ that will turn the field into a ‘laughingstock.’” None of them were willing to go on record with their concerns for fear of retaliation. Reflecting on the ongoing debate over psychiatric diagnosis, Allen Frances was reminded of medieval maps that had notations such as “dragons live here” in places where their knowledge was lacking. “We have a dragon’s world here. But you wouldn’t want to be without that map.”

09/9/15

The Quest for Psychiatric Dragons, Part 1

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© dvarg | 123rf.com

In her book, Opening Skinner’s Box, author Lauren Slater related a conversation she had with Robert Spitzer, one of the most important psychiatrists of the twentieth century. She told him of the personal struggles of another individual that Spitzer was historically linked to, David Rosenhan. Slater told Spitzer that Rosenhan’s wife had died of cancer, his daughter had died in a car crash and he was paralyzed from a disease that doctors couldn’t diagnose. She reported that Spitzer’s response was: “That’s what you get for conducting such an inquiry.”

There are questions regarding the truth of what Slater reported here. Spitzer himself said that he doesn’t remember saying that. And if he did, he meant it in a joking way. However, Slater’s observation that “Rosenhan’s study is still hated in the field [of psychiatry] after forty years” is very true. In his recently published book Shrinks, Jeffrey Lierberman, a former president of the American Psychiatric Association, described Rosenhan at the time of his infamous study as “a little-known Stanford-trained lawyer who had recently obtained a psychology degree but lacked any clinical experience.” He thought the 1973 Rosenhan study had fueled an “activist movement that sought to eliminate psychiatry entirely.” See “A Censored Story of Psychiatry” Parts 1 and 2 for more on Rosenhan’s study and Lieberman’s portrayal of it.

In 1973, the American Psychiatric Association (APA) was in crisis. Gay activists had actively protested at the annual APA meetings between 1970 and 1972, seeking to have the APA remove homosexuality as a mental disorder from the DSM. Robert Spitzer, the architect of the diagnostic revolution that was codified in the DSM-III, related in an interview that he was at a symposium on the treatment of homosexuality in 1972 that was disrupted by a group of gay activists. He recalled that in effect, the activists were saying they wanted the meeting to stop; because “You’re pathologizing us!” The media attention of the above protests created a very public embarrassment for psychiatry. Kirk et al., in Mad Science, commented:

An entire group of people labeled as mentally ill by the American Psychiatric Association was disputing its psychiatric diagnosis. At the core of their challenge was a simple, east-to-understand question: why was homosexuality a mental illness?

Spitzer approached one of the protesters after the symposium was cancelled and their conversation led to a meeting between some of the activists and an APA committee Spitzer was a member of, the APA Task Force on Nomenclature and Statistics. Spitzer recalled that the gist of the meeting was “the idea that the only way gays could overcome civil rights discrimination was if psychiatry would acknowledge that homosexuality was not a mental illness.” After the meeting with the Nomenclature and Statistics Task Force, Spitzer proposed the APA organize a symposium at the annual APA meeting in May of 1973. He continued to be active with this issue within the APA, and was responsible for the position statement (formulated on June 7, 1973 by Spitzer) that was approved by the APA Board of Trustees in December 1973 removing homosexuality as a diagnosis from the DSM.

Concurrent with this issue was the fallout from the publication of David Rosenhan’s article in the January 1973 issue of Science, “Being Sane in Insane Places.” Kirk et al. noted that the study was intriguing, easy to understand and had striking results. So it received a lot of media attention. The study reinforced the view that psychiatric judgments were inadequate, and even laughable. “Once again, the target of the joke was the scientific pretence of psychiatric diagnosis: Psychiatrists could not distinguish the sane from the insane.”

Jeffery Lieberman, a former president of the APA and author of the book Shrinks, said that an emergency meeting of the Board of Trustees was called in February of 1973 “to consider how to address the crisis and counter the rampant criticism.” Lieberman related how the APA Board of Trustees realized the best way to deflect the “tidal wave of reproof” was to make a fundamental change in how mental illness was conceptualized and diagnosed. They agreed that the most compelling means would be to transform the DSM. By the end of the emergency meeting, the trustees had authorized the creation of the third edition of the DSM.

Lieberman said Robert Spitzer wanted to be in charge of the revision process as soon as he heard it had been approved. Spitzer recalled,  “I spoke to the medical director at the APA and told him I would love to head this thing.”  In part because of the way he handled the quandary over homosexuality, Spitzer was appointed to chair the DSM-III Task Force in 1974. But he had already positioned himself as an expert on psychiatric diagnosis.

I think it is fair to say that Spitzer had been aiming towards this appointment for almost seven years. His association with the DSM began in 1966, when he agreed to take notes for the DSM-II committee. Then Spitzer et al. introduced use of the kappa statistic into the literature on psychiatric diagnosis in their 1967 study, “Quantification of Agreement in Psychiatric Diagnosis.” In The Selling of the DSM, Stuart Kirk and Herb Kutchins commented that the introduction of kappa appeared to provide a way to unify the comparison of reliability studies, while eliminating the statistical problem chance agreement at the same time. Joseph Fliess, who would later co-author with Spitzer their seminal 1974 study, was one of the authors here.

Before the Rosenhan study in 1973, Spitzer and others had already published several articles related to revising psychiatric diagnosis in the Archives of General Psychiatry: “Immediately Available Record of Mental Status Exam” (July, 1965);  “Mental Status Schedule” (April 1967); “Quantification of Agreement in Psychiatric Diagnosis: A New Approach” (July, 1967); “DIAGNO: A Computer Program for Psychiatric Diagnosis Utilizing the Differential Diagnostic Procedure” (June, 1968); “The Psychiatric Status Schedule” (July, 1970); “Quantification of Agreement in Multiple Psychiatric Diagnosis” (February, 1972). And these were just those published in the Archives.

In 1971 Spitzer was introduced to a group of psychiatric researchers from Washington University in St. Louis. They were working to develop diagnostic criteria for specific mental disorders. Spitzer was in heaven. Lieberman reported Spitzer said: “It was like I had finally awoken from a spell. Finally, a rational way to approach diagnosis other than the nebulous psychoanalytical definitions in the DSM-II.” According to Whitaker and Cosgrove in Psychiatry Under the Influence, more than half of the members Spitzer appointed to the DSM-III Task Force had an existing or past affiliation with Washington University.

Feighner et al., the group of researchers at Washington University in St. Louis, published “Diagnostic Criteria for Use in Psychiatric Research” in 1972. They proposed specific diagnostic criteria for 14 psychiatric disorders, along with the validating evidence for those criteria. Kirk and Kutchins said their work became known as the Feighner criteria, after its senior author. This study became a classic in the psychiatric literature, and has been cited over 4,000 times since its publication.

In 1978, Spitzer and others would use the Feighner criteria to produce the “Research Diagnostic Criteria”  (RDC), another significant step in the formation of the DSM-III. Kirk and Kutchins said: “These two articles … and the work on which they were based are among the most influential developments in psychiatry” since the late 1960s. An important fact in both the Feighner criteria and Spitzer’s RDC, was they were initially developed only for use in research. “Neither article proposed that the elaborate diagnostic systems be adopted by clinical psychiatrists.” That came later. But you can see the path that Spitzer had been walking since 1967. He wanted to radically change psychiatric diagnosis and had been methodically moving in that direction. And then the Rosenhan study, “Being Sane in Insane Places” was published in the journal Science.

12/24/14

Where There’s Smoke …

As much as 4 ½ years before the publication of the DSM-5, there was growing public criticism of the American Psychiatric Association (APA) and the process they used to develop it. The amazing thing about this criticism is that it was from within the ranks of psychiatry itself … by psychiatrists who had been in charge of previous revisions of the DSM.

In a 2008 article, Benedict Carey of the New York Times pointed out the importance of the DSM as a “medical guidebook and a cultural institution.” It is used to help doctors make diagnoses and to provide diagnostic codes to insurance companies. The National Institute of Mental Health made the use of DSM criteria a requirement for funding research. But for the first time, the APA required its DSM contributors to sign a nondisclosure agreement.

Research psychiatrist Robert Spitzer said that when he first heard about the agreement, he went “bonkers.” Spitzer said: “Transparency is necessary if the document is to have credibility, and, in time, you’re going to have people complaining all over the place that they didn’t have the opportunity to challenge anything.”

Robert Spitzer, the chair of the “landmark” third edition of the DSM, has been hailed as the rescuer or savior of psychiatry. Allen Frances, the chair of the 4th edition of the DSM said in his book, Saving Normal, that Spitzer was a rare man. “Without Robert Spitzer, psychiatry might have become increasingly irrelevant.” Even critics of modern psychiatric diagnosis, such the authors of the book Mad Science, acknowledge Spitzer’s importance to psychiatry: “Robert Spitzer was a most unlikely rescuer of American psychiatry.”

On June 26, 2009, Frances published an article in the Psychiatric Times where he identified what he saw a grave problems with the DSM-5. He also was critical of the lack of transparency. Pointing to his own efforts with the DSM-IV, he said their goal had been to ensure that everyone would understand what they were doing and how they were going about it. “There was explicit accountability for decision making on all changes.” He cautioned against the stated ambition to effect a “paradigm shift” in psychiatric diagnosis with the DSM-5.

So long as psychiatric diagnosis is stuck at its current descriptive level, there is little to be gained and much to be lost in frequently and arbitrarily changing the system. Descriptive diagnosis should remain fairly stable until, disorder by disorder, we gradually attain a more fundamental and explanatory understanding of causality.

Frances specified his concerns with the DSM-5 process, which included the following: 1) there was no scientific basis to justify a paradigm shift in psychiatric diagnosis at this time; 2) there was a failure to provide clear methodological guidelines on the level of empirical support for the changes; 3) there was a failure to be open to wide scrutiny and useful criticism; 4) there was a failure to set and meet clear timelines; there was a likelihood that time pressure would lead to an unconsidered rush on last-minute decisions.

The members of the APA working on the DSM-5, including the DSM-5 Chair, David Kupfer, responded APA to Frances on July 1, 2009. They suggested that both Spitzer and Frances were repeating “factual errors and assumptions” about the development of the DSM-5. After their refutation of the concerns expressed by Frances, they stated:

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.

Robert Spitzer responded to the criticisms raised about Allen Frances and himself on July 2, 2009. Spitzer noted how the DSM-5 debate had taken an ugly turn, by suggesting that he and Frances were critiquing the DSM for financial reasons. He limited his comments to what he saw as the core issue of transparency. After raising a series of questions with regard to the opaqueness and “empty rhetoric” on the DSM-5 as the most open and inclusive DSM ever, Spitzer saw two possible reasons for the lack of transparency. First, the answers to his questions were known, but for some reason, the DSM leadership was withholding it; perhaps to shield themselves from criticisms. A second possibility was that the DSM-5 leadership didn’t know the answers to his questions. “Given their plan to publish DSM-V in May 2012, if the second possibility is the case, it is inconceivable that this publication deadline could realistically be met. “

Both Spitzer and Frances continued their challenges to the process of review and approval of the DSM-5 by the APA and gained more support and even some victories. You can also read a more detailed description of the dispute here. The publication of the DSM-5 was delayed until May of 2013, but the controversy merely grew. Allen Frances became one of the most vocal critics of the DSM-5, with multiple blogs and articles looking at the problems and concerns. He’s even written two books, Saving Normal and Essentials of Psychiatric Diagnosis as a result of this controversy. You can scroll through some of his articles on the Huffington Post for starters.

Oh and with regard to the veiled accusation of Spitzer and Frances criticizing the DSM-5 for financial reasons, David Kupfer, Chair of the DSM-5 Task Force, has been outed for failing to report financial interests in Adaptive Testing Technologies, a company that designs tests and implements large scale adaptive testing systems for mental health assessment. After an investigation, the APA said (Letter-to-Assembly-20140114.pdf): “Dr. Kupfer should have disclosed to APA his interest in PAI in 2012.” However, it did not find that his interest in PAI had any influence on DSM-5’s inclusion of dimensional measures for further study in Section 3. One blogger, 1 Boring Old Man said:

It seems like Dr. Kupfer et al. are pursuing a strategy of only acknowledging this particular Conflict of Interest when forced, as in the situation with JAMA Psychiatry, and avoiding talking about it otherwise – mirrored so far by the APA President and Board of Trustees.

 

07/23/14

Creation of a Psychiatric Disorder

I became interested in the history of Premenstral Dysphoric Disorder (PMDD) when I met two husbands in marital counseling who believed their wife’s mood changes during menstruation caused most of their fights. They even kept track of their wife’s menstrual cycle and charted it in conjunction with their marital conflict.

Robert Spitzer, the “creator of the modern DSM” was the first to propose that severe PMS symptoms should be classified as a psychiatric disorder. According to Alix Spiegel of NPR, Spitzer has personally conceived of more mental disorders “than any other living person on the face of the earth.” But despite his efforts, in June of 1986 the APA Board of Trustees voted against making PMDD (then known as Late Luteal Phase Dysphoric Disorder, LLPDD) an official DSM diagnosis. This outcome was largely through the efforts of people like Paula Caplan.

Caplan and others opposed adding LLPDD to the DSM–III-R and later the DSM-IV. They (rightly) felt it would pathologize women. Caplan gives a detailed description of her efforts to keep LLPDD and out of the DSM in her book, They Say You’re Crazy.

But LLPDD was added to a specially created appendix of the DSM-III-R for “provisional categories needing further study.” Following the advice of Robert Spitzer, it was also given an official number just like the approved diagnoses in the main part of the manual. Psychiatrists were encouraged to use the diagnosis as if it was official. LLPDD even appeared in the main text of the DSM-III-R, where only fully tested and scientifically supported diagnoses were supposed to be included.

When the DSM-IV was published in 1994, LLPDD was renamed as PMDD and kept in the appendix. But PMDD was still a pseudo-diagnosis in the sense that it was still in the appendix and not in the main section of the manual.

About one year before Eli Lilly’s patent rights were about to run out on Prozac (fluoxetine) in August of 2001, the FDA approved Serafem to treat the pseudo-diagnosis of PMDD. Although both Zoloft and Celexa had been used to “treat” PMDD, Serafem was the first prescription drug that the FDA said could be marketed specifically for treating PMDD. What were these changes that warranted the approval of a newly patented form of fluxetine for Eli Lily? In “Sarafem: The Pimping of Prozac for PMS” Alicia Rebensdorf said:

The company changed the color of the pill from green to girly pink and turned the depression-stigmatized label Prozac to the oh-so-feminine name Sarafem. Yet Sarafem/Prozac both require daily 20 mg. doses of fluoxetine hydrochloride. You don’t take Sarafem any less often. You don’t take it any smaller doses.

Here are the first two Serafem commercials.

With the publication of the DSM-5, PMDD finally came out of the closet appendix. In their recent article reviewing the DSM history of PMDD, Peter Zachar and Kenneth Kendler commented: “When the DSM-5 was published in 2013, PMDD was moved to the main section of the manual as a diagnosis approved for routine clinical use.” But functionally, it was approved for “routine clinical use” when Spitzer and the APA gave it a DSM number and created an appendix for it in 1987 as LLPDD. The reason that officially moving PMDD to the main section was not controversial was because the above actions placed it there in 1987, BEFORE THE RESEARCH INTO PMDD as a psychiatric disorder was done.

According to Caplan in a May 12 1986 press conference, Robert Spitzer admitted that there no proposed treatment for PMDD/LLPDD at that point. However, “that is the very reason we need to put the category in the DSM, because that will make it possible to conduct research to find out what will help.” So PMDD had to be coined as a disorder so research could be done to help women with a disorder … that wasn’t yet an official disorder. As Zachar and Kendler said:

By the time that the DSM-5 development process began, PMDD was no longer a new diagnosis, and conservatism favored keeping it a disorder subject to routine clinical use. The approval of Sarafem played a role, but so did giving PMDD an official code number in the DSM-IV and listing it in the main text as an example of mood disorder NOS.

This history of how PMDD became a DSM diagnosis illustrates the unscientific manner in which many psychiatric disorders are created. Paula Caplan cautioned that the danger of the DSM is that it is used with so little monitoring of when the line is crossed from normalcy to disorder in its decisions.

In his essay, “Mental Illness is Still a Myth,” Thomas Szasz said that psychiatrists have succeeded in persuading us that the conditions they call “mental disorders” are diseases—phenomena independent of human motivation or will. “Until recently, only psychiatrists—who know little about medicine and less about science—embraced such blind physical reductionism.”

Does the DSM need independent monitoring and accountability?