09/16/15

The Quest for Psychiatric Dragons, Part 2

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 because of 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 fake patients 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.”

07/15/15

Pathologizing Grief

In January of 2015, an article on “Complicated Grief” was posted in The New England Medical Journal blog. The author described complicated grief as “intense grief after the death of a loved one that lasts longer than expected according to social norms and causes functional impairment.” While it was said that psychotherapy is a first-line treatment, the author reported that antidepressant medication is commonly used. This is just the latest stage in a rather complicated refashioning of grief from a normal human experience into a mental disorder.

The symptoms of complicated grief were said to be: “persistent, intense yearning, longing, and sadness.” Along with these “symptoms” can be a sense of disbelief or failure to accept the reality of the person’s death. Persistent thoughts or images of the deceased can occur. Ruminating on the circumstances of the death, with feelings of anger or guilt was said to be common. Avoiding situations that remind the person of the loss is common. Holding on to the deceased by repeated reminiscing, viewing, touching or smelling the deceased person’s belongings can occur as well.

People with complicated grief often feel shocked, stunned, or emotionally numb, and they may become estranged from others because of the belief that happiness is inextricably tied to the person who died. They may have a diminished sense of self or discomfort with a changed social role and are often confused by their seemingly endless grief.

Complicated grief is not a psychiatric diagnosis, although you wouldn’t know that from reading the above description. It explicitly uses diagnostic-like language in its discussion in an attempt to gain legitimacy for “Prolonged Grief Disorder” to be included in the International Classification of Diseases, 11th edition, due for release in 2017. The boat has passed on inclusion in the DSM, which went through its own controversy over grief when the DSM-5 removed the bereavement exclusion (BE) from the existing Major Depression Disorder (MDD) in 2013.

Within the DSM, the bereavement exclusion meant that a diagnosis of MDD could not be made if the loss of a loved one was a better explanation for the observed symptoms of depression. However, the time frame to avoid the grieving process from qualifying as MDD has been progressively shrinking. Within the DSM-III, the BE was one year; within the 4th edition, it was two months. Now in the DSM-5, bereavement is no longer an excuse. If you meet the diagnostic criteria for MDD over a two-week time period, you are just as depressed as anyone else, according to the DSM.

Joanne Cacciatore, who has specialized in the psychotherapeutic treatment of grief and bereavement for almost twenty years, has been an outspoken critic of these changing guidelines and pseudo-diagnoses. In March of 2012 she wrote an essay opposing the proposed elimination of the BE from the DSM-5. Her eloquent essay reached 100,000 readers in two weeks. She stated her opposition to both of the above ‘time limits’ for grief, and pointed to the historical movement of the DSM to medicalize normal human emotion. She said:

We should not, ethically or morally, medicalize grief. To do so is to medicalize love. We rarely mourn for that which we do not love. I can only begin to imagine what the sages, and mystics, and shamans of the past might think of a society which does so.

Allen Frances was also openly critical of the DSM-5 and its changes with regard to bereavement. In his own blog on the Huffington Post in March of 2012, he published Dr. Cacciatore’s open letter to the Board of Trustees of the American Psychiatric Association. She pointed to the arbitrariness of the two-week time frame, stating that it not only contradicts common sense, but rests on weak scientific evidence. To her knowledge there was no empirical evidence to support it.

One thing in which the literature is clear: long-term psychological distress is common in this population and other populations suffering traumatic deaths. In my experience both as a researcher and clinician in the field and also as a bereaved parent, the DSM-5 proposal is radical, unnecessary, challenges what it means to be human, and for some may be dangerous.

But the APA was not moved. Frances tried again in January of 2013, as the DSM-5 was preparing to go to press at the end of the month. He said: “The American Psychiatric Association has just four more weeks to reverse this dreadful mistake that flies in the face of clinical common sense and is unsupported by the limited available science.” He put together his own top ten list of harmful changes in the DSM-5, and medicalizing grief was number two. In case you aren’t aware, Dr. Frances’ credibility in voicing these concerns come from his long career as a psychiatrist and as the person selected by the APA to chair the DSM-IV. He said:

After 40 years and lots of clinical experience, I can’t distinguish at two weeks between the symptoms of normal grief and the symptoms of mild depression — and I challenge anyone else to do so. This is an inherently unreliable distinction. And I know damn well that primary care doctors can’t do it in a 7-minute visit. This should have been the most crucial point in DSM-5 decision-making because primary care docs prescribe 80 percent of all antidepressants and will be most likely to misuse the DSM-5 in mislabeling grievers.

Returning now to the essay “Complicated Grief,” let’s look at Dr. Cacciatore’s response. She commented how the bereaved were again at risk of being diagnosed and “treated” for “absolutely normal feelings and experiences” after a painful and traumatic loss. Responding to the above description of complicated grief, she said:

Ha! Social norms? Around grief? Talk about pathology! Western culture’s “social norms” and expectations around grief, especially when traumatic, are as abnormal and avoidant as any society could get. The average bereavement leave is three days, many bereaved parents are medicated within days or weeks after a traumatic loss (even in the presence of data to suggest these medications can be harmful and iatrogenic), and mourners are expected, and then pressured, to get back to ‘life-as-usual’ often within weeks or mere months, even after traumatic death. And our social networks often fail as others’ tolerance wanes in the months and years that follow.

Perhaps there is better guidance for conceiving a time frame for grief and bereavement in the book of Ecclesiastes (3:1-8) than in the DSM. There the Preacher said there is a season and a time for everything under heaven. Notice that he doesn’t try and quantify “season” or “time.” A time to be born and a time to die; a time to weep and a time to laugh; a time to mourn and a time to dance; a time to keep silent and a time to speak. When weeping turns to laughing, when mourning is replaced by dancing, then the season of grief has run its course. However, when individuals attempt to pathologize human emotion by blurring the line between grief and psychiatric disorder, it is a good thing that people like Joanne Cacciatore and Allen Frances choose to speak up and not remain silent.

03/18/15

Modern Alchemy with Antidepressants

A study published in the open access journal, PLOS One by Sugarman et al. once again replicated previous studies showing that there was very little clinical difference between an antidepressant and placebo. In a way this is old news. One of the study’s authors, Irving Kirsch previously reported these findings. You can read more on this antidepressant research here and here. I’ve also looked at a 60 Minutes broadcast that interviewed him in “Thor’s Psychiatric Hammer: Antidepressants.” Kirsch has also published a book on the topic: The Emperor’s New Drugs: Exploding the Antidepressant Myth. But here is the significance of the Sugarman et al. study. It was the first evaluation to use “a complete database of published and unpublished trials sponsored by the drug’s manufacturer.”

In 2004, GlaxoSmithKline (GSK) was required as part of a lawsuit settlement to post online the results of all clinical trials involving its drugs. The 2004 lawsuit was because the company had withheld data on the ineffectiveness and potential danger of Paxil (paroxetine) when given to adolescents and children. But it doesn’t seem GSK learned their lesson. In 2014 the company agreed to plead guilty to criminal charges and pay $3 billion in fines for promoting its antidepressant drugs, Paxil and Wellbutrin for unapproved uses and failing to report safety data about Avandia. So Sugarman et al. were able to use the data GSK made available to do the research reported here.

The current analysis is the first evaluation of the efficacy of an SSRI medication in the treatment of multiple anxiety disorders, and the first to utilize a complete database of published and unpublished trials sponsored by the drug’s manufacturer. Our results indicated that paroxetine presented a modest benefit over placebo in the treatment of anxiety and depression, with mean change score differences of 2.3 and 2.5 points on the HRSA [Hamilton Rating Scale for Anxiety] and HRSD [Hamilton Rating Scale for Depression], respectively.

The study’s results found that individuals receiving placebo reported 79% of the magnitude of change with the individuals receiving paroxetine. This was consistent to previously reported magnitudes of 76% for placebo compared to paroxetine. Replicating this previous finding, namely greater than 75% of the drug response, suggested that: “the magnitude of the placebo effect is especially large in the treatment of anxiety and depression.” Given the similarities between paroxetine and other SSRIs, it is possible that similar magnitudes of placebo effects will be found with them. Further research is required to support this proposition. Nevertheless, “the current analysis indicates that the published literature represents an overestimate of the true efficacy of paroxetine in the treatment of anxiety.”

The glass-half-full reporting of the differences between drug and placebo have emphasized that statistically significant differences were found. The problem is, those differences were so small, that their clinical significance was questionable. According to the criteria of NICE, the National Institute of Health and Clinical Excellence, “the mean difference between paroxetine and placebo in the current analyses fell short of clinical significance for the treatment of both anxiety and depression.” Sugarman et al. reviewed these concerns and concluded that changes of three points or less on the HRSD did not correspond to a clinically detectable change and appeared to be “of marginal clinical significance.”

So paroxetine has only a slight benefit over placebo in treating symptoms of anxiety and supports previous work indicating that it has just a modest benefit over placebo when treating depression. Given the known side effects with standard medications used to treat anxiety and depression, their use as a first-line treatment for these problems seems questionable. “The obvious alternative for the treatment of both anxiety and depression is psychotherapy intervention.” But direct comparisons have not generally shown a significant difference between depression treatment modalities (medication or psychotherapy). Similarly inconclusive findings were noted for anxiety treatment.

Allen Frances said there were two differences between medieval alchemy and the pharmaceutical industry today. First is the well-oiled, massively financed, worldwide, and devastatingly effective marketing machine. Second is the requirement for a DSM diagnosis.

A significant portion of the $12 billion spent each year on antidepressants in the United States rewards the drug companies for promoting the overly widespread use of what to many patients are no more than highly advertised, oversold, and very expensive placebos prescribed for a fake diagnosis. (Allen Frances, Saving Normal)

In 2010, there was a study published a Scandinavian psychiatric journal with the provocative title: “Antidepressant Medication Prevents Suicide in Depression.” It concluded from studying 18,922 suicides in Sweden between 1992 and 2003, “that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.” Sixteen months after publication, it was formally retracted by the authors for “… unintentional errors in the analysis of the data.”

Psychologist Phillip Hickey reported that after a five month legal battle, he was able to get access to the correct data. The original study found that among completed suicides treated for depression in psychiatric care in the last five years before their suicide, 164 (15.2%) had antidepressants in their blood when they committed suicide. The corrected data indicated that 603 (56%) had antidepressants in them when they committed suicide. The “unintentional error” was huge—an increase of 439 people (268%).

And yet, the study’s author said that no conclusion from the study could be drawn “regarding antidepressants’ effects on suicide risk in any direction.” In other words, you couldn’t conclude that antidepressants prevented or facilitated suicide risk. Hickey reported that at the time of writing the original article, its author has financial ties to Lundback, Eli Lily and GSK (GlaxoSmithKline).

In another study, found in The British Journal of Psychiatry, a team of UCLA researchers randomized 88 participants into double-blind groups for 8 weeks of treatment (placebo or medication) with supportive care; and a separate group receiving supportive care alone. Expectations of medication effectiveness, general treatment effectiveness and therapeutic alliance were also measured. The groups receiving medication or placebo plus supportive care were not significantly different. However, both had significantly better outcomes than the supportive care alone group. Expectations of medication effectiveness were predictive of only the placebo response. Therapeutic alliance predicted participant response to both medication and placebo.

The lead author of the study, Andrew Lechter, said that the results indicated that if you think a pill is going to work, it probably will work. He noted that belief in the effectiveness of the medication was not related to the likelihood of benefitting from it. “Our study indicates that belief in ‘the power of the pill’ uniquely drives the placebo response, while medications are likely to work regardless of patients’ belief in their effectiveness.” He speculated that factors like direct-to-the-consumer advertising could be shaping peoples’ attitudes about medication. “It may not be an accident that placebo response rates have soared at the same time the pharmaceutical companies are spending $10 billion a year on consumer advertising.”

It seems that Lechter is saying that the drug response was independent of the expectations of medication effectiveness, while the placebo response was driven be the prior expectations of the participants, as they were influenced by factors like direct-to-the-consumer advertisings. If true, this would seem to challenge, to a certain extent, the results noted above and in Kirsch’s previous research. Replication of the results is needed before Lechter’s conclusions from his research are accepted. It should be pointed out that paroxetine (Paxil) was approved by the FDA in May of 1996, while direct-to-the-consumer advertising of medications did not begin until 1997. Therefore, it would not have had an effect upon the paroxetine data reported above. I would also feel more comfortable with Lechter’s interpretations of his data if he didn’t have as extensive an association with the pharmaceutical industry. See the “Declaration of interest” in the linked abstract from The British Journal of Psychiatry.

01/12/15

Can Addicts Stop Using Without Help?

Maia Szalavitz wrote on Substance.com that she stopped shooting coke and heroin when she was 23. “I quit at around the age when, according to large epidemiological studies, most people who have diagnosable addiction problems do so —without treatment.” Although she personally got treatment help, her article was about people who stop without treatment or assistance from self-help, 12-Step programs. It was provocatively titled: “Most People with Addiction Simply Grow Out of It: Why Is This Widely Denied?” She’s currently finishing her sixth book, Unbroken Brain, “which examines why seeing addiction as a developmental or learning disorder can help us better understand, prevent and treat it.”

Szalavitz referenced an epidemiological study, which suggested that a significant proportion of individuals achieve remission from addiction at some point in their lifetime. This study by Lopez-Quintero et al. found that “half of the cases of nicotine, alcohol, cannabis and cocaine dependence remitted approximately 26, 14, 6 and 5 years after dependence onset, respectively.” An article by Gene H. Heyman reviewed four studies, including the Lopez-Quintero one, and suggested that: “most addicts were no longer using drugs at clinically significant (emphasis added) levels by the age of 30.” According to Heyman:

The idea that addiction is a disease characterized by compulsive (involuntary) drug use goes hand in hand with the belief that addicts require lifelong treatment and that treatment is necessary for recovery. However, the epidemiological results indicate that most addicts do not take advantage of treatment; nevertheless, most quit. The logical inference is that remission from drug dependence does not require treatment.

The implications of Heyman’s and Szalavitz’s interpretation of the research studies they cited has far reaching consequences, particularly for the addiction treatment industry. So I want to take a look at these epidemiological studies that led them to conclude that most addicts quit drug or alcohol use (or enter remission) on their own. Heyman’s review article looked at four national epidemiological surveys of the prevalence of psychiatric disorders. Szalavitz seems to cite references to these same four studies or other articles by Heyman. So my interaction will be with the discussion in Heyman’s article: “Quitting Drugs: Quantitative and Qualitative Features.”

Hyman presented data from four large national epidemiological studies that reported high remission rates of diagnosed substance-related disorders. The studies and their remission rates were as follows: 76% for NCS, the National Comorbidity Survey; 83% for the NCS-R, the National Comorbidity Survey Replication; and 81% for the NESARC, the National Epidemiological Survey on Alcohol and Related Studies. Another study, the Epidemiological Catchment Area (ECA) survey reported a lower remission rate of 57%, but had combined the criteria for substance abuse and substance dependence into one category. He concluded: “The results do not support the often heard claim that addiction is a chronic, relapsing disease.”

Now I also have problems with defining addiction in pure medical/disease model terms and would be happy to see a more socially and cognitively nuanced definition of addiction become mainstream. But those self-generated remission rates seemed awfully high. How was this remission quantified?

First, let’s look at a critique of epidemiological miscounts by Allen Frances. Frances was the chair appointed by the American Psychiatric Association for the fourth edition of the DSM, the Diagnostic and Statistical Manual of Mental Disorders used by the epidemiological researchers to quantify their definition of “remission.” He initially pointed to an article by Regier et al., “Limitations of Diagnostic Criteria and Assessment Instruments for Mental Disorders” published in the journal, Archives of General Psychiatry in 1998. The Regier et al. article abstract raised concerns with “significant differences in mental disorder rates from 2 large community surveys”—the ECA and the NCS, two of the studies cited and discussed by Heyman.

Frances also presented his critique of epidemiological studies that use DSM diagnoses in Saving Normal. There he pointed to the “inherent limitations” of defining clinical cases in epidemiological studies. They used lay interviewers who make “diagnoses” by symptom counts, with “no consideration of whether the symptoms are severe or enduring enough to warrant diagnosis or treatment.” As a consequence, the judgment of a clinician is missing. “This results in rates that are always greatly inflated.” Symptoms “that are mild, transient and lacking in clinical significance” are mistakenly diagnosed as symptoms of psychiatric disorder.

They should never be taken at face value as a true reflection of the real extent of illness in the community. Unfortunately, the exaggerated rates are always reported without proper caveat and are accepted as if they are an accurate reflection of the real prevalence of psychiatric disorder. (Saving Normal, p. 86)

Another problem with these studies was how they defined “remission.” Remission was simply not reporting the required number of symptoms to meet the diagnosis over the previous year. Remission had a broader meaning than just “quitting” or abstinence.

The diagnostic criteria for substance abuse and dependence found in the DSM-IV were used by all the studies reported in Heyman. The ECA study, as noted above, included individuals who were “substance abusers” and “substance dependent.” The other studies only looked at those who were “substance dependent.” Remission for the ECA study was defined as no reported symptoms, while in the others, it was defined as two or less. This was based upon the separate criteria needed for each diagnosis—only one from the list for substance abuse, but three for substance dependence.

In Mad Science, Kirk, Gomory and Cohen noted how the DSM’s diagnostic criteria are the de facto definitions of mental disorder in the U.S. However, they said that describing a set of behaviors and labeling them as symptoms or diagnostic criteria does not establish the presence or absence of an illness or disorder.

Descriptive diagnosis is a tautology that distracts observers from recognizing that DSM offers no indicators that establish the validity of any psychiatric illness, although they may typically point to distresses, worries or misbehaviors (Mad Science, p. 166).

So the importance of clinical judgment, pointed to by Frances, in making a diagnosis of the existence or remission of substance dependence or substance abuse is essential. Following the critique of Frances and Regier et al. and their concerns with inconsistencies and limitations of using diagnostic criteria in epidemiological studies, the reported incidence rates of both substance dependence AND remission are likely to be greatly inflated in the studies reviewed by Heyman.

The conclusion that large populations of individuals with diagnosable addiction problems (substance dependence, according to Heyman) can stop or remit without help in such high percentages is suspect. In addition, the “diagnosis” of individuals as substance dependent in these studies is probably inaccurate for many of them. It is likely that many of those labeled as substance dependent in the studies were only substance abusers. According to Carlton Erickson in The Science of Addiction, substance abusers are more likely to make changes in their substance use because of “significant impairment or distress in their life as a consequence of their use.” They may quit on their own, without treatment. They may even go back to moderate or controlled drinking or mature out of the habit.

01/7/15

Pharma and Its Golden Hoard

© Chrisjeanes | Dreamstime.com - Smaug - The Hobbit Photo — © Chrisjeanes | Dreamstime.com – Smaug – The Hobbit Photo

The debate over the cost of drug development goes all the way back to the late 1950s. The then Chairman of the U.S. Senate’s Anti-Trust and Monopoly Subcommittee said that the pharmaceutical industry had: 1) predatory pricing and excessive margins related to their patents; 2) that extravagant increases in costs and prices were due to large expenditures in marketing; and 3) most of the industry’s new products were no more effective than the ones already on the market. It seems that little has changed over the past fifty-five years.

An often-quoted 2003 study on the cost of drug development by DiMasi et al., “The Price of Innovation,” concluded that it cost an estimated $802 million in 2000 dollars to bring a new drug to market. The 2014 profile released by PhRMA, the advocacy group for the U.S. pharmaceutical industry, estimated that it cost $1.2 billion to develop a new drug. PhRMA noted that: “some more recent studies estimate the cost to be even higher.” In contradiction of the higher R&D estimates of DiMasi and PhRMA, Light and Warburton suggested that: “R&D costs companies a median of $43.4 million per new drug.” This is less than 1/18th of the $802 million estimate by DiMasi et al.

Deciding whose figures to trust can be tricky. For example, Light and Warburton pointed out that the Tufts Center for the Study of Drug Development, where the DiMasi study was conducted, has received “substantial industry funding for years.” Among the concerns they had with the DiMasi study were: inflated costs for drug trials; exaggerated time for R&D; corporate financial risk for R&D was much lower than reported; average costs based on “means” and not “medians,” leading to inflated figures. Using the median trial costs reported by DiMasi (74% of the mean trail costs), they said: “the $802 million figure would have been reduced to $593 million had median costs been used.”

Scott Gavura in “What Does a New Drug Cost” part 1 looked at both the DiMasi study and its critique by Light and Warburton. Gavura said he found the Light and Warburton figure “implausibly small.” In “What Does a New Drug Cost” part 2, he elaborated, saying that he thought their estimates “were based on a sequence of highly implausible assumptions;” the average drug development cost would be higher in the real world. He asked if the low-hanging fruit in drug development is gone. “A growing concern with the pharmaceutical industry is its overall productivity in delivering new drugs.” Gavura concluded his article by stating that he thought criticism of the pharmaceutical industry was justified, if it was done for the right reasons.

Being skeptical of R&D estimates is wise. Data on individual drugs is not transparent, and estimates must incorporate a number of assumptions which have the potential to bias the conclusions. This lack of transparency fuels suspicion of the process. But we should also be equally skeptical of arguments that dismiss or diminish the growing problems with R&D. There is good evidence to suggest that drug development is a risky, expensive endeavor, and that this work is getting harder.

In a 2008 article published in PLOS Medicine, “The Cost of Pushing Pills,” Gagnon and Lexichin explored the reported expenditures of the pharmaceutical industry and concluded that: “pharmaceutical companies spend almost twice as much on promotion as they do on R&D.” Their estimate was made from highly reliable sources, one of them being IMS Health, a company relied upon by both the federal government and the pharmaceutical industry for information on the healthcare industry.

Their revised estimates for promotional spending in the US for 2004 was $57.5 billion, twice that of IMS Health. This compares to the $31.5 billion reported by the National Science Foundation for domestic industrial pharmaceutical R&D in 2004. “These numbers clearly show how promotion predominates over R&D in the pharmaceutical industry, contrary to the industry’s claim.”

Allen Frances, the chair of the DSM-IV, has become an outspoken critic of modern psychiatry, the DSM-5, and “Big Pharma.” He reported in Saving Normal that worldwide pharmaceutical sales exceed $700 billion each year. Half of that figure is spent in North America and another one fourth in Europe. Rick Newman reported that Pharma’s profit margin was 16.4 percent, the seventh highest among the industries tracked by Morningside, an independent investment research firm.

The justification of high prices and huge profits by pharmaceutical companies was “mostly fluff,” according to Frances. “Drug pricing has no relation to real cost or value and instead reflects Pharma’s monopoly position in the market and its dominance over politicians.” At its worst, he said that pharmaceutical research is a “deceptive shell game” meant to seduce and mislead doctors and the public. “The claim that drugs are so expensive because they require so much research is pure smoke screen.”

In The Desolation of Smaug, the final scene shows the dragon Smaug rising up out of molten gold. Goaded by the unsuccessful attempt of the dwarves to destroy him, he flies off to take his revenge on the unsuspecting Lake-town of Esgaroth. Over the past sixty years we have allowed Pharma to gather a golden hoard through its profits from drug development. Like Smaug, Pharma jealously guards its hoard. If we take on a quest to right this injustice, we must be careful not to loose an angry, vengeful dragon upon an unsuspecting humanity by mistake.

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 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; now removed from the APA website): “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.

12/3/14

To Use or Not Use Antidepressants

I ran across a report from the National Center for Health Statistics when reading Saving Normal by Allen Frances that had some incredible facts about antidepressant use in the United States. The report said that 11% of Americans 12 years and over take antidepressant medication. Women were 2.5 times as likely to take antidepressants as men. Individuals 40 and over are more likely to take antidepressants than those younger than 40. “Twenty-three percent of women aged 40-59 take antidepressants, more than any other age-sex group.”

When the severity of depressive symptoms was considered, use of antidepressant medication rose as the severity of symptoms increases. This seems logical; the worse your depression is, the more likely you are to try medication. But look at the other end of symptom severity—7.6% of those taking antidepressants have NO REPORTED symptoms of depression. The Data Brief pointed out that this group could include people taking antidepressants for reasons other than depression and those who are being “successfully” treated with antidepressants, and just don’t have any symptoms currently. See the table below.

Depressive symptoms	Percent
Total
None	7.6
Mild	19.2
Moderate	28.4
Severe	33.9
Males
None	4.4
Mild	11.5
Moderate	18.6
Severe	21.0
Females
None	10.9
Mild	24.6
Moderate	34.5
Severe	39.9

Allen Frances suggested that part of the problem was that drug companies capitalized on the placebo effect, that is: “people getting better because of positive expectations independent of any specific healing effect of the treatment.” Treating the “worried well” expanded the customer pool and guaranteed a pool of satisfied customers. “Placebo responders often become long-term loyalists to medication use even when the medication is perfectly useless.”

The best way to get great results with a pill is to treat people who don’t really need it—the highest placebo response rates occur in those who would get better naturally and on their own.

What’s at stake? The Statistics Portal indicated that the top ten selling antidepressants in 2011-2012 grossed 8.5 billion dollars. Considering that most of the antidepressants are off patent and not as profitable to the drug companies, this is an incredible haul. Another indication of the pervasiveness of antidepressant use in the U.S. is to look at the number of prescriptions written. The top antidepressant drugs in the U.S. based upon the number of dispensed prescriptions in 2011-2012 are given in the following chart, again from The Statistics Portal.

Antidepressants	Prescriptions
Celexa (citalopram hydrobromide)	39,087,000
Zoloft (sertaline hydrochloride)	37,893,000
Prozac (fluoxetine hydrochloride)	24,961,000
Trazadone (trazadone hydrochloride)	23,449,000
Cymbalta	18,468,000
Lexapro	16,367,000
Paxil (paroxetine hydrochloride)	13,834,000
Effexor (venlafaxine hydrochloride ER)	13,679,000
Wellbutrin (bupropion hydrochloride XL)	13,365,000
Elavil (amitriptyline hydrochloride)	12,880,000

Returning to the NCHS Data Brief, once people start taking antidepressants, they tend to continue taking them. Sixty-one percent of Americans taking an antidepressant have been taking it longer than 2 years; 13.6% have been taking them ten or more years. The problem is that the widespread use of antidepressants and their long-term use may be actually causing depression.

Robert Whitaker commented in Anatomy of an Epidemic that prior to the appearance of antidepressant drugs, depression was seen as a rare problem with typically good outcomes over time. Now the NIMH says that an episode of major depression “can occur only once in a person’s lifetime, but more often, a person has several episodes.” In 2012, an estimated 16 million adults and 2.2 million adolescents had at least one depressive episode in the past year.

Whitaker noted how Italian psychiatrist, Giovanni Fava began in 1994 to look at the changing face of depression. In that article, Fava raised the possibility that “long-term use of antidepressant drugs may also increase the biochemical vulnerability to depression and decrease its likelihood of subsequent response to pharmacological treatment.” In a 2003 article, Fava suggested that antidepressants may, in some cases, actually cause depression. “Whether one treats a depressed patient for 3 months or 3 years, it does not matter when one stops the drugs. A statistical trend suggested that the longer the drug treatment, the higher the likelihood of relapse.”

In a 2014 article, “Rational Use of Antidepressant Drugs,” Fava said that rational use of antidepressant drugs should consider all the potential benefits and harms. They should only be used with the most severe and persistent cases of depression. They should be used for the shortest possible duration. Using antidepressants to treat anxiety disorders should be reduced, unless a major depressive disorder is present or other treatments have been ineffective.

These suggestions may seem to be radically different from current guidelines such as those of the American Psychiatric Association, but they reflect the weighing of risk, responsiveness and vulnerability that should be applied to the use of AD [antidepressant drugs] in each individual case.

To use or not to use antidepressants, that is the question. There is serious potential harm that may occur with their use. And sometimes they can literally save a life. What seems to be clear is that current guidelines for their use can, in the long run, worsen the problem they were originally supposed to “treat.” Along with the above suggestions for the rational use of antidepressants given by Fava, I think there needs to be a change in how we think about psychiatric drugs. The current disease-centered model of drug action needs to be replaced by a drug-centered model of drug action. You can find more on this distinction in the writings of Joanna Moncrieff, such as The Myth of the Chemical Cure and my article, “A Drug is a Drug is a Drug.” Also see two longer articles on antidepressants available in the Counseling Issues section under the “Resources” link of this site.

09/24/14

The Making of an American Tragedy

Psychiatrist Peter Breggin said that diagnosing millions of children with ADHD and then treating them with stimulants and other psychoactive chemicals is an American tragedy. “Never before in history has a society attempted to deal with its children by drugging a significant portion of them into conformity while failing to meet their needs in the home, school and society.” According to Dr.Breggin, the ethical scientist and physician, the concerned parent “must feel stricken with grief and dumbfounded” that our society has allowed this to happen to our children.

In October of 2011, the American Academy of Pediatrics (AAP) overrode the FDA and approved diagnosing children as young as four with ADHD and medicating them with Ritalin. The lead author of the report said: “Because of greater awareness about ADHD and better ways of diagnosing and treating this disorder, more children are being helped.” Dr. Breggin said this action was an outrage: “This endorsement of drugging younger children by the American Academy of Pediatrics is an outrage.”

According to Dr. Breggin, the scientific literature shows that 50 percent or more of children this young will become depressed, lethargic, weepy—along with being more manageable when given medications such as Ritalin, Adderall and other ADHD medications. Studies show that stimulants will permanently change brain chemistry in the children, cause shrinkage of brain tissue and predispose them to cocaine addiction in young adulthood. He also feared this endorsement by the AAP would open the door for every other psychiatric drug being prescribed to children that young.

These new guidelines will encourage prescribers to throw caution to the wind with toddlers, opening a Pandora’s box of drug intervention for children. Many young children will have their brains bathed with powerful and often toxic chemicals in the early years of their central nervous system development.

But the problems didn’t stop there. Susanna Visser, who oversees the CDC research on ADHD, presented a report at the Georgia Mental Health Forum in May of 2014 that suggested at least 10,000 2 and 3 year-olds were being medicated for ADHD. “It puts these children and their developing minds at risk, and their health is at risk.” Effective non-drug treatments were often ignored.

Families of toddlers with behavioral problems are coming to the doctor’s office for help, and the help they are getting too often is a prescription for a Class II controlled substance, which has not been established as safe for that young of a child.

As liberal as the AAP guidelines for ADHD are, they do not even address diagnosis in children 3 and younger—let alone the use of stimulant medications—with that age group. Children under 4 are not covered in the guidelines because “hyperactivity and impulsivity are developmentally appropriate for toddlers.” Dr. Lawrence Diller, a pediatrician, said: “People prescribing to 2-year-olds are just winging it. It is outside the standard of care, and they should be subject to malpractice if something goes wrong with a kid.”

Sheila Matthews attempted to put “the insanity of drugging 2-3 year olds” in perspective. She noted that the average weight for male toddlers at three years was 29.5 pounds; female toddlers averaged 28.4 pounds. “By this age, only 80 percent of the child’s brain has fully developed.” Kids at this age are learning to arrange things in groups, to put things in size order, remembering what they did yesterday, learning to say please and thank you, and recognizing themselves in the mirror. “In a nutshell, 2-3 year old toddlers are being labeled with an alleged mental illness that is not based in science or medicine and then “treated” with extremely addictive, mind-altering drugs before their brains are even fully formed.”

Psychiatrist Allen Frances said: “Treating babies with stimulants is based on no research, is reckless, and takes no account of the possible harmful long-term effects of bathing baby brains with powerful neurotransmitter drugs.” He hoped that the CDC report would fuel a backlash of parental and professional protest as it becomes clearer how absurdly overused is the ADHD diagnosis and stimulant medication. “It is also particularly outrageous that so many of the thought leaders promoting the excessive use of stimulants have such close ties with pharmaceutical companies.”

Dr Breggin lamented that instead of meeting the normal needs of our children, we are suppressing them with drugs. The average parent or teacher has no idea that what is presented as medical treatment “is actually a form of medical child abuse.” What they see is a more manageable child and assumes this is for the best. Instead, it is the making of an American tragedy.

08/13/14

The Dumbest “Diagnosis” Ever

Copyright: ximagination / 123RF Stock Photo — ximagination / 123RF Stock Photo

Is your child drowsy/sleepy at times? Do you see signs of daydreaming, mental confusion, slowed thinking or behavior, lethargy or apathy? Don’t worry; it may just be the early signs of Sluggish Cognitive Tempo (SCT)! By some estimates, SCT is present in two million children. While still not acknowledged as an official psychiatric disorder, the January 2014 issue of The Journal of Abnormal Child Psychology devoted the entire issue to SCT. Be patient, it will eventually become an official childhood psychiatric disorder, if its advocates have their way. And then you will have a brand new reason to give your son or daughter stimulant medications.

If you think this satire is too off-the-wall, read the April 11, 2014 article in the NYT by Alan Schwartz, “Idea of New Attention Disorder Spurs Research, and Debate.” Schwartz said that “Experts pushing for more research into sluggish cognitive tempo say it is gaining momentum toward recognition as a legitimate disorder—and as such, a candidate for pharmacological treatment.” He added that some of the identified symptoms so far in the research “have helped Eli Lily investigate how its flagship A.D.H.D. drug might treat it.” The psychiatric drug industry has excelled at expanding the market for its drugs, generating tremendous wealth for many.

Becker, Marshall and McBurnett did a search of journal articles (for their own article in January 2014 issue of The Journal of Abnormal Child Psychology) and found that “very few papers explicitly examined or even mentioned SCT between 1985 and 1999.” Since then there has been a steady increase in the articles that either focused on SCT or mentioned it in the body of the paper. They observed that while symptoms of under-arousal and low levels of mental energy were noticed to be part of attention deficit as early as 1798, it wasn’t until the 1970s that inattention was seen as causing even more impairment than hyperactivity. By the mid-1980s, “empirical support for the SCT dimension separate from inattention emerged.”

Russell Barkley, one of the most influential advocates for ADHD, noted in his article for the special issue of The Journal of Abnormal Child Psychology that there was a dearth of studies on SCT. Students now entering the profession could make a successful research career specializing in the research of SCT. He felt there would surely be an increased demand for such empirically-based research in view of the clinical referrals already occurring; and the anticipated increase in the near future as the general public becomes aware of SCT. “The fact that SCT is not is not recognized as yet in any official taxonomy of psychiatric disorders will not alter this circumstance given the growing presence of information on SCT at various widely visited internet sites such as YouTube and Wikipedia, among others.”

Alan Schwartz reported in his NYT article that Barkley has said that SCT “has become the new attention disorder.” Barkley also has financial ties to Eli Lily, receiving $118,000 from 2009 to 2012 for consulting and speaking engagements. He has also published a symptom checklist to identify adults with the condition. The forms are available for $131.75 apiece from Guilford Press. Oh, and Barkley also edits sluggish cognitive tempo’s Wikipedia page. The SCT Wikipedia page carried the following note at the top of the page on June 20th, 2014: “A major contributor to this article appears to have a close connection with its subject. It may require cleanup to comply with Wikipedia’s content policies.”

One of the SCT researchers, David McBurnett, said a scientific consensus on SCT could be many years in the future. “We haven’t even agreed on the symptom list—that’s how early on we are in the process.” And yet, Dr. McBurnett recently conducted a clinical trial funded and overseen by Eli Lilly to see if the proposed SCT diagnosis could be treated with Straterra, the company’s primary ADHD drug. Published in The Journal of Child and Adolescent Psychopharmacology in November of 2013,his study concluded: “This is the first study to report significant effects of any medication on SCT.”

This process with SCT reminded me of what Robert Whitaker depicted in Anatomy of an Epidemic. He showed that in order to sell our society on the benefits of psychiatric drugs, “Psychiatry has had to grossly exaggerate the value of its new drugs, silence its critics, and keep the story of poor long-term outcomes hidden.” This has meant telling a false story to the American public, and then actively hiding research results that reveal the poor long-term outcomes with a drug-centered paradigm of care. Whitaker said it was a conscious, willful process that exacts a horrible toll on our society.

The number of people disabled by mental illness during the past twenty years has soared, and now this epidemic is spreading to our children. Millions of children and adolescents are being groomed to be lifelong users of these drugs. This grooming happens by twisting childhood behaviors like daydreaming, slowed thinking or behavior, and lethargy into symptoms of a new so-called childhood psychiatric disorder.

Allen Frances, chair of the fourth edition of the DSM, said that “’Sluggish Cognitive Tempo’ may possibly be the very dumbest and most dangerous diagnostic idea I have ever encountered . . . .The risk that it could do great harm is real . . . .The last thing our kids need is to be misdiagnosed with ‘Sluggish Cognitive Tempo’ and bathe in even more stimulants.”

Still not convinced? Listen to this pod cast by Peter Breggin where he interviews psychologist Fred Ernst about Sluggish Cognitive Tempo and the “psychiatric assault” on children through psychiatric medication.

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag: Allen Frances