1 Boring Old Man

Better Antipsychotic Adherence Could Save Governments Millions

PsychiatricNews

by Vabren Watts,

March 3, 2015

[full text on-line]

&

Improving Antipsychotic Adherence Among Patients With Schizophrenia: Savings for States

Psychiatric Services in Advance:
Economic Grand Rounds

by Zachary S. Predmore, Soeren Mattke,, Marcela Horvitz-Lennon

January 2, 2015

[full text on-line]

Absract: This column presents findings of an analysis conducted to quantify the potential net savings to state budgets from interventions to improve adherence to antipsychotic drugs among patients with schizophrenia. Using a financial model based on published data, the authors estimated costs of direct medical care and criminal justice system involvement at state and national levels and validated it against findings from other cost studies. The model estimated an annual cost of $21.4 billion [in 2013 dollars] to Medicaid programs and other state agencies for people with schizophrenia. On the basis of data on the effect on outcomes of increased medication adherence, better adherence could yield annual net savings of $3.28 billion to states or $1,580 per patient per year. Innovations to improve adherence to antipsychotic drugs among schizophrenia patients can yield substantial savings in state budgets. States should consider interventions shown to increase medication adherence in this patient group.

Research has shown that several interventions improve antipsychotic adherence among persons with schizophrenia. Some of these studies have also provided direct evidence of the cost-effectiveness of these interventions. A recent study of patients with schizophrenia in the United Kingdom demonstrated that even small financial incentives [less than $25 per patient per month] increased adherence to antipsychotic medications from a baseline of 69% to 85%…

Replacing traditional oral therapy with long-acting injectable [LAI] antipsychotics has been shown to increase adherence… Thus using generic LAI antipsychotics could save more than $1,000 per patient per year…

Medication management programs, such as counseling by pharmacists or advanced practice nurses, are another potential method for increasing adherence. Two specific medication management programs — cognitive adaptive training, which attempts to change patients ’ behavior by modifying their home environment through use of signs, alarms, and checklists, and electronic medication monitoring, a computerized system that reminds patients to take their medications and tracks adherence — have also been shown to increase adherence to antipsychotics among patients with schizophrenia to 92%, compared with 73% adherence in the group that received treatment as usual…

1. Practice Guideline for the Treatment of Patients With Schizophrenia [APA 2004]
2. Guideline Watch [APA  2009]
and from the NIMH RAISE Project [now adopted by SAMHSA]
3. Individual Resiliency Training Manual [NIMH 2014]

In my view, these are problems that have no general solution at present. If I hadn’t been a Straw Man in these discussions so frequently [I should say Straw Psychiatrist], I could work up a real dander about this report/recommendation. Instead, I’ve developed a hobby to occupy myself during debates of this kind – some way to silence my mind [and mouth] to keep me out of a dead-end discussion. I think about the impossibility of the problem as framed [I think that’s called being a contrarian if you say it out loud], or about why trying to answer it is a double bind. And I particularly try to think about the cases being brought up as exceptions as people wax eloquently pro and con. I tell myself that such reflections remind me of the essential impossibility of psychotic experience and illness; they remind me that the only real solutions come on a case by case basis and they are tentative; and thinking privately keeps me out of run-on arguments that I don’t want to be in. But sometimes, I find an opinion in there that seems right to me. This may be one of those times. This scheme has been tried, and it just didn’t work…

Dr. Mattke has received speaker fees and travel support from Janssen Diagnostics. The other authors report no financial relationships with commercial interests.

Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation:
A Systematic Review

by Giovanni A. Fava, Alessia Gatti, Carlotta Belaise, Jenny Guidi, and Emanuela Offidani

Psychotherapy and Psychosomatics. 2015 84:72-81.

[full text on-line]

[supplementary material]

Background: Selective serotonin reuptake inhibitors [SSRI] are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated.

Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: ‘withdrawal symptoms’ OR ‘withdrawal syndrome’ OR ‘discontinuation syndrome’ OR ‘discontinuation symptoms’, AND ‘SSRI’ OR ‘serotonin’ OR ‘anti- depressant’ OR ‘paroxetine’ OR ‘fluoxetine’ OR ‘sertraline’ OR ‘fluvoxamine’ OR ‘citalopram’ OR ‘escitalopram’. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014.

Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse.

Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome’ that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome’.

In the past decade, few studies assessed the presence of discontinuation symptoms, and the topic has attracted limited attention also as to literature reviews. To the best of our knowledge, in the English language there has been no systematic review on the clinical aspects of SSRI discontinuation according to established criteria. Yet, such knowledge is important because of the wide-spread use of SSRI in medical practice.

As a psychiatry resident [1974-1978], my references for psychiatric drugs were textbooks, under an inch thick. They’re still around with the kind of underlining that you look back on and wonder what you thought you were doing. Almost everything ended up underlined or high lighted – like you could vacuum up the information with a yellow felt pen. But my point is that I don’t recall the drugs changing at some rate that required constant updating. There were the MAOIs and the TCAs [Monamine Oxidase Inhibitors and the Tricyclic Antidepressants]. They were laid out in neat tables with various columns of characteristics, describing how they differed. They were primarily inpatient drugs, used primarily on patients with the various melancholic depressions, but not so much for outpatients. We all knew the side effects because the patients told us about them all the time. While I never saw a fatality, we all worried about overdoses because a month’s supply prescription could be a fatal dose. I remember a rule of sorts – if a patient responded to an antidepressant, they should continue for at least six months because patients who stopped sooner had an increased incidence of relapse. But my point is that these weren’t long term drugs because depression wasn’t considered a long term problem and the everyday side effects – things like dry mouth and constipation were gladly left behind.

When the DSM-III and the SSRIs came along, things were different. Depression became a Disorder, Major Depressive Disorder, and the treatment became the antidepressant drugs that flowed from the pipeline. They were better tolerated and the old short-term rules just sort of evaporated. People stayed on them for long periods and thought of them as treating some kind of disease they had. Many seemed to think of them as keeping the disease at bay, and were afraid that if they stopped, it would come back. If they got depressed again, they said "my antidepressant has stopped working." I missed most of that, and a lot of what I learned about those drugs was from patients talking about their experiences. And there was a pattern. First there would be a "occasionally" symptom like decreased libido with Prozac®. Then it was "sometimes", then "often." I learned about withdrawal from a friend’s wife who had a hell of a time getting off of Paxil®. At first, I thought it was a Paxil® thing, but then I heard about it with other drugs. And so it went, learning from patients before it came from the traditional sources like journals. I actually learned most of what I know about SSRI withdrawal here from the comments of Altostrata and her Surviving ADs site – things like the withdrawal symptoms being interpreted as the "depression is coming back" or always tapering with discontinuation rather than stopping abruptly. That information is available now, but not "back in the day."

New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal

An Editorial

by Guy Chouinard and Virginie-Anne Chouinard

Psychotherapy and Psychosomatics. 2015 84:63–71.

[full text on-line]

Conclusion: SSRIs have provided major therapy advancement in the treatment of depression and other mental disorders. Withdrawal symptoms may occur with SSRIs, similarly to other CNS drugs, and they must be identified and differentiated from relapse and recurrence of the original illness. The proposed diagnostic criteria will permit the identification of three types of withdrawal associated with SSRIs. Differentiating withdrawal from relapse and recurrence of the original illness will allow clinicians to more effectively reduce and withdraw SSRIs, and find a minimal therapeutic dose. It is most important to recognize persistent post·withdrawal disorders to prevent unnecessarily high doses and prolonged treatment.

This paper set me to thinking about something. It’s a report of something I need to know about, but it’s 25+ years after I needed to know about it. The first article on withdrawal listed in Fava et al’s supplementary material is in 1988, around the time Prozac® was introduced, and there are number in the 1990s. But I didn’t learn about it through medical channels. As an old man, I have the time to root around about things, but I sure didn’t in 1988. And yet, in my first career [Medicine] and early in the second [Psychiatry] I just knew about things. I didn’t think about "keeping up." I just read my journals, went to meetings and conferences, and lived in a world populated by colleagues and patients. There was always a library around for looking up things I had questions about. I never much liked CME [Continuing Medical Education], so I picked things "of interest" rather than review courses. My point is that I didn’t think about "keeping up." Medical life just "kept me up." That seems to have changed in the 1980s. I wish I’d been perceptive enough to notice it happening. I’d always read review articles, but I no longer found them very interesting. Too upbeat. Too pie in the sky. Too future oriented. I don’t recall ever thinking about why, but I just gradually stopped that kind of general journal reading and read books of interest.

^{Note: This post isn’t like most of my others. I’m not in the habit of simply saying what I think without documentation, or in areas this far outside of my area of expertise. But I’ve got a really strong feeling here. Take it for what it’s worth – just a strongly felt, definitively stated, but nonetheless speculative feeling… Maybe it’s a polemic too – my polemic… I titled and ended the last post <to be continued>… not just because I was going to have more to say on the topic, but because it’s the only thing I’m absolutely sure of – that this debate will keep on and on just like it has since the dawn of 1boringoldman time [in psychiatry] and for that matter, before…}

po·lem·ic
noun

1. A controversial argument, especially one refuting or attacking a specific opinion or doctrine.
2. A person engaged in or inclined to controversy, argument, or refutation.

A polemic is a contentious argument that is intended to affirm a specific understanding via attacks on a contrary position. Polemics are mostly seen in arguments about very controversial topics. The art or practice of such argumentation is called polemics… The word is derived from Greek polemikos, meaning "warlike, hostile", from polemos, meaning "war".

• “Understanding Psychosis and Schizophrenia” and mental health service users
  PLoS Blog: Mind the Brain
  by James Coyne
  February 26, 2015
• Understanding Psychosis and Schizophrenia: a critique by Laws, Langford and Huda
  The Mental Elf
  by Keith Laws, Alex Langford, and Samei Huda
  November 27, 2014
• The comments by Bernard Carroll here and here

on medications

1. Practice Guideline for the Treatment of Patients With Schizophrenia [APA 2004]
2. Guideline Watch [APA  2009]
and from the NIMH RAISE Project [now adopted by SAMHSA]
3. Individual Resiliency Training Manual [NIMH 2014]

on the medical model and diagnosis

In storm duties… I talked about the bio·psycho·social model suggested by George Engel that, in my opinion, was never really implemented. It’s my "medical model" of choice. I would agree with the BPS that diagnosis can be stigmatizing and either used or experienced as an indictment. It can and has been used to imply an etiology when, in fact, none is known. And people can be misdiagnosed. Even worse, the categorical criteria can be intrinsically flawed [as they definitely are in the DSM-III+ with depression]. Those are all bad things to avoid or even preach against on any available pulpit. But the BPS report suggests that for those reasons, we should abandon categorization altogether, any model that underlies that categorization with it, and goes on to argue that the category doesn’t really exist, but simply represents phenomena along a spectrum with normal mental life.

I have no great love for the DSM-III+, but in this case, I think they did a decent job. First, the diagnosis was initially the gloomy Dementia Praecox popularized by Emil Kraepelin in 1893. In 1911, Eugen Bleuler re-evaluated the syndrome and coined the term Schizophrenia. He described a broad spectrum of people, presentations, and outcomes including complete recovery following a psychotic episode. With Bleuler, diagnosis was not destiny. In the 1980 DSM-III, they separated out Brief Reactive Psychosis and added duration and functional impairment to make sure that the diagnosis didn’t rest on symptoms alone, though they didn’t name a pathognomonic symptom [a symptom that is unique to a syndrome that nails the diagnosis]. I happen to think there is one – the complex described as negative symptoms [though they are inadequately described in the DSMs]. I’ve not seen a case where I was able to explore the history in depth and the negative symptoms weren’t present in some form or another long before the outbreak of frank psychosis [I’m including kids I grew up with and kids of my friends who later developed the classic disorder].

Treatment of negative symptoms begins with assessing the patient for syndromes that can cause the appearance of secondary negative symptoms. The treatment of such secondary negative symptoms consists of treating their cause, e.g., antipsychotics for primary positive symptoms, antidepressants for depression, anxiolytics for anxiety disorders, or antiparkinsonian agents or antipsychotic dose reduction for extrapyramidal side effects. If negative symptoms persist, they are presumed to be primary negative symptoms of the deficit state. There are no treatments with proven efficacy for primary negative symptoms.

At times, some people may appear inexpressive, withdrawn, listless, apathetic or unmotivated. They may find it difficult even to find the energy to prepare food or generally to look after themselves. Traditionally these difficulties have been thought of as ‘negative symptoms’: part of an illness. However, they can often be a result of feeling overwhelmed by experiences and trying to cope, or arise from feelings of helplessness and depression. They can also be unwanted effects of the drugs that people are often prescribed

Speaking of the dawn of 1boringoldman time, on the first day I was a psychiatry resident, I was assigned several patients who were already on the acute ward where we worked. The first one I met was a twenty something year old mother of three who had been brought to the hospital after drowning one of her sons to death in the lake in Atlanta’s central park. She had been stopped by bystanders during her attempt to drown the second one, directed to do so by the voice of God. By the time I met her, she had been declared NGRI [not guilty by reason of insanity] and was awaiting definitive placement. She’d been there for a while, and was an obvious favorite of the nurses – a long-stay patient on a short-stay unit. One of the nurses took me aside and asked that I have my sessions with her at times other than between 3PM and 5PM when she watched the after-school children’s programs. The nurse called it "being with her kids" – something she had done with her children daily when they got home from school. The other patients intuitively complied and left the day room to her or sometimes even watched with her.

By the time I met Gloria, she was not psychotic. She would answer questions about what happened with her kids, but didn’t really engage the topic. Her family visited often, and they didn’t talk about her son’s death either. Like the nurses, there was always a tear nearly visible as their looks conveyed both the tragedy and their love. The thing that most struck me about her was her flattened affect and her literalness. She was on a low dose of a first generation neuroleptic which might’ve explained some of the emotional flattening, but I doubted that. It seemed like part of being her. We were taught in those days to assess abstracting ability by asking the meaning of proverbs. She had no idea what they meant. I’m not even sure she got the point of my asking. And her general literalness was pervasive in all conversaton – striking even to my then untrained ear. I awkwardly asked her mother about those things. I think I was wondering if the medication was responsible. But her mother knew exactly what I was asking and said something like, "Oh no, she’s always been like that! I only wish I’d known where it was headed!" And cried painful tears.

I didn’t know it then, but Gloria was the nidus for what I now think about this affliction. As dramatic and disruptive as the psychosis of Schizophrenia can be, I no longer think of it as primary, though it can certainly be an overwhelming and sometimes insurmountable problem. I see the baseline state as the primary affliction – what people call "negative symptoms" or Eugen Bleuler called "Anhedonia." It’s what I was trying to get at in birdman…. To Gloria’s literalness [living in a world without abstract meanings] and her difficulty experiencing or accessing an emotional compass, I would now add a confusion in reading and understanding the subtle but ubiquitous metacommunications in interpersonal experience. Those things contribute to the oft-expressed sense of non-being, of identity diffusion, of confusion, of deadness, or the many other ways people try to explain something that others rarely ever even think about because for them, it is intuitively present and operating automatically. I tried to talk about this in 1. from n equals one…, 2. from n equals one…, 3. from n equals one…, etc. with another example. I know that if a person showed up seeking psychotherapy with just those complaints without psychosis in the story, I’d still be likely to give it my best shot. Those things alone are heavy burdens to carry into a life, particularly a life among people.

I’m not trying to mount an antecdote war here, just trying to give an example. Effective psychotherapy requires a shared view of what the problem is, and is informed by the nature of the problem. Patients can learn how to identify, live with, compensate for, or even change what happens in these states of confusion if that’s the focus of the work. I’ve never seen a patient who came for a therapy who was hurt or demeaned by talking about negative symptoms [again the never word]. They already know about them – every day. And I worry that any approach that doesn’t take them on as a central focus will flounder much in the same way as relying only on medications does. In fact, some of the examples in their own report address these very problems and I was glad to see that. End of sermon.

on rights and laws

on etiology

Their traumatic theory is as speculative as some of the biological theories. I personally doubt its primacy, but how about some proof before NICE buys into the radical change in mental health policy suggested. Chasing trauma has had a powerful pull throughout history [and brought down some of the best of us], but only really worked in patients with clear PTSD as specifically defined. Having spent a career treating a lot of traumatic illness, I don’t personally think that Schizophrenia is primarily a post-traumatic syndrome – certainly not without some solid consistent evidence.

It’s not easy to respond to the British Psychological Society’s [BPS], Understanding Psychosis and Schizophrenia, primarily because of the extensive use of negation throughout the report. In their discussion, the phenomena formerly called a symptom [like hearing voices] is not abnormal, but rather something seen in normal mental life. A negative symptom like anhedonia is not some primary aspect of a disease state but rather the result of being overwhelmed. There is not any underlying condition causing symptoms [the Szaszian formulation of the Myth of Mental Illness]. Medication is not treating some underlying pathology, but rather an optional adjunct some find helpful. Much of what is seen in these conditions is the result of being not understood or not listened to. In the etiologic dimension, the report suggests that these are people who have been traumatized by life experiences – not a flight into fantasy but a reaction to fact.

The points made in the report are certainly well known to all of us. Besides echoing the words of Thomas Szasz [who is nowhere mentioned in the report], it’s a position similar to the one expressed by Robert Whitaker in his books and by the bloggers on his web-site, Mad in America [Whitaker is referenced extensively in the report]. It also mirrors the ideas of the Recovery Movement and the Psychiatric Survivors Movement. The phrase coined in the report that seems to define the approach being generally advocated is "We need to replace paternalism with collaboration." In the section about recovery colleges, there’s a table contrasting these models as discussed in this report:

Section 13: What mental health services need to do differently
   13.1 We need to move beyond the ‘medical model’
   13.2 We need to replace paternalism with collaboration
   13.3 We need to stop ‘prescribing’ and start supporting people to choose
   13.4 We need to make rights and expectations explicit
   13.5 We need to reduce the use of compulsion and mental health legislation
   13.6 We need to change the way we do research
   13.7 We need to change how mental health professionals are trained and supported

While I’m focusing on the overall thrust of the report, James Coyne of the PLoS blog, Mind the Brain, has addressed the content and I’d recommend looking at his take on the specifics of the report [“Understanding Psychosis and Schizophrenia” and mental health service users].

1. Practice Guideline for the Treatment of Patients With Schizophrenia [APA 2004]
2. Guideline Watch [APA  2009]
and from the NIMH RAISE Project [now adopted by SAMHSA]
3. Individual Resiliency Training Manual [NIMH 2014]

Just for clarification, there are two central medical models of disease. The one being referred to here holds that signs [things you see] and symptoms [things reported] are external manifestations of an internal cause [a disease]. Diagnosis is focused on locating the underlying cause [which is also the object of treatment, if possible]. Treatment of the symptoms themselves is a secondary focus. There are several corollaries. Aesculapian Authority refers to the traditional physician role – the assumption that the physician may recommend doing something painful or counterintuitive, but that recommendation has Therapeutic Intent and operates under the principle of Primum non nocere – "first, do no harm." Obviously, this BPS report questions the appropriateness of this model when applied to psychotic mental illness as well as the applicability of the corollaries.

Section 14: What we all need to do differently
14.1 We need take on board that we’re all in this together – there is no ‘us’ and ‘them’
14.2 We need to focus on prevention
   14.2.1 Prevention: towards a safer society
   14.2.2 Prevention: towards a more equal society
   14.2.3 Prevention: reducing discrimination and oppression
   14.2.4 Prevention: reducing harmful drug use and addressing its causes
   14.2.5 Prevention: what we can each do to protect our mental health
14.3 We need to campaign against prejudice and discrimination

^{Georgia Morning}

A few years back, I made an attribution error [Adolf Meyer [1866-1950]…]. I credited Adolf Meyer, the influential early American Psychiatrist with the bio·psycho·social model. It was an easy error to make. Meyer’s model was psycho·biology and Meyer’s wife was a major founding figure in American Social Work. But looking back, it highlights how sometimes big things are happening all around you, but you’re too caught up in your own scene to see them:

The Need for a New Medical Model: A Challenge for Biomedicine

by George L. Engel

Science. 1977 196[4286]:129-136.

[full text on-line]

At a recent conference on psychiatric education, many psychiatrists seemed lo be saying to medicine, "Please take us back and we will never again deviate from the ‘medical model.’" For, as one critical psychiatrist put it, "Psychiatry has become a hodgepodge of unscientific opinions, assorted philosophies and ‘schools of thought,’ mixed metaphors, role diffusion, propaganda, and politicking for ‘mental health’ and other esoteric goals". In contrast, the rest of medicine appears neat and tidy. It has a firm base in the biological sciences, enormous technologic resources at its command, and a record of astonishing achievement in elucidating mechanisms of disease and devising new treatments. It would seem that psychiatry would do well to emulate its sister medical disciplines by finally embracing once and for all the medical model of disease.

But I do not accept such a premise. Rather, I contend that all medicine is in crisis and, further, that medicine’s crisis derives from the same basic fault as psychiatry’s, namely, adherence to a model of disease no longer adequate for the scientific tasks and social responsibilities of either medicine or psychiatry. The importance of how physicians conceptualize disease derives from how such concepts determine what are considered the proper boundaries of professional responsibility and how they influence attitudes toward and behavior with patients. Psychiatry’s crisis revolves around the question of whether the categories of human distress with which it is concerned are properly considered "disease" as currently conceptualized and whether exercise of the traditional authority of the physician is appropriate for their helping functions. Medicine’s crisis stems from the logical inference that since "disease" is defined in terms of somatic parameters, physicians need not be concerned with psychosocial issues which lie outside medicine’s responsibility and authority…

The Clinical Application of the Biopsychosocial Model

BY GEORGE L. ENGEL,, M.D.

American Journal of Psychiatry. 1980 137[5]:535-544.

[full text on-line]

Engel was actually a figure in my own life back in the day. I was an internist who had discovered that practicing medicine wasn’t quite like it had been in training. Following the patients from beginning to end, I quickly realized that there was more to doctoring than the science of disease I had learned, because the persona and the life of the patient had so much more to do with the treatment of patients than was apparent in the environment where I trained. I had learned about disease from the knowledge gained from groups united by diagnosis, but practicing medicine was with one patient at a time, and the one part was a lot bigger factor than I might have ever imagined. Engel was an internist who had become a major figure in psychiatry and psychosomatics. I had read his work and considered applying to psychiatry in Rochester where he was because he was there when I decided to add psychiatry to my skillset. But after spending three years in Europe as a soldier, I think I was ready to come home, and ended up in Atlanta where, unlike Rochester, today’s snow is considered a blizzard [‘southern born and southern bred‘ as they say]. I finished my psychiatry residency in 1977 and by 1979 & 1980, I was directing a residency, in Analytic training, and way too busy to know about the coming storm. I went to neither APA Convention [1979, 1980]. The young faculty like me stayed at home and kept the home fires burning.

So when Dr. Carroll said in his comment yesterday, "… we can agree about the historical failure consistently to implement the biopsychosocial model in the care of patients with schizophrenia", he wasn’t kidding. I really didn’t know that Engel had introduced that model during and as part of the controversies that swirled around in those days when the DSM-III was in the works. Thinking about it now, from my perspective I’m not sure it was consistently or fully implemented anywhere – period.

Southern storm duties call me right now. Wood for the fire, etc. But I think it’s a good place for me to take a breather and gather my thoughts. In the meantime, I refer you to the debate that went on in the comment section of my post which side of the street?…. It’s well worth the read both for content and how such exchanges should be conducted – respectfully…

^{I call it "winter park benches with chiminea"}

I saw Birdman or (The Unexpected Virtue of Ignorance) Saturday night, one day before the Oscars, and by Sunday night, I was rooting for it to win, even though it was in the running with some other amazing films. In Atlanta, we had [still have] a film series at Emory called Movie Mania, attended by members of the Mental Health Community and trainees at large in the many different programs in the area. It’s only a matter of time before Birdman will be on the screen in one of those discussions – guaranteed. It’s a classic, in the genre and league with One Flew Over the Cuckoo’s Nest, but unlike that film [or A Beautiful Mind, or Shutter Island, or the King of Hearts] – in Birdman, neither Psychosis nor any kind of Mental Health anything is ever mentioned.

As much as I would love to talk on and on about this film, a Blog is no place to ruin a movie for those who haven’t seen it. So I’ll just make a few comments. In the movies, we all cheer for these characters played by Michael Keaton, Jack Nicholson, Russel Crowe, Leonard DiCaprio, and Alan Bates [Martin Scorsese’s Shutter Island may be an exception, but you’ll have to see it to know why]. We all cheer for the protagonists, even with their often tragic endings – everyone in the audience, including the psychiatry residents who then leave the film series to go back to the Emergency room and have to deal with the out of control psychotic people brought by the police, or by distraught family and friends [see this comment on the last post for their dilemma].

The brilliance of Birdman is that it’s not about mental illness, it’s about an aging actor who is searching for an authentic connection with life by adapting a serious drama [by Raymond Carver] about the power of love and connectedness on Broadway. His real success in life had been in his role in a series of popular heroic fantasy films in which he played the caped Birdman – a superhero with superpowers – but he lead something of a meaningless life otherwise with angst and failed relationships. We learn in the opening scene that, in private, he actually has Birdman’s superpowers, hears the voice of the character Birdman, and at times he actually becomes Birdman [again in private] under stress. So Michael Keaton [who was the first film Batman], is a character who contains the psychotic dilemma without anyone medicating him or anyone enthusiasticly aiming him towards recovery. He doesn’t even have a mental illness. He’s just a guy that can’t experience his sense of being in life, and also secretly is a superhero, but doesn’t feel his life in that role either.

I’m about to tell the end of the movie. I don’t think it will interfere with seeing it, but if you hate spoilers, bookmark this post and come back after you’ve seen it. By the way, see it for sure. When you see it, first read the blurb about Raymond Carver’s life. And pay particular attention to the Edward Norton and Emma Stone characters, who, like a Greek Chorus, narrate the dilemma throughout the film in their own lives. ‘I only feel real on the stage, not in my life.’

Keaton’s character achieves authenticity by using a real gun in the ending suicide scene on the opening night of the play. He doesn’t die, but shoots off his nose. While he achieves critical acclaim, it’s a hard act to follow obviously. Looking in the mirror in the hospital, he sees his reconstructed nose which is radically different [looks like a beak]. As a matter of fact, we notice that his bandages look like the Birdman mask. Seeing some birds, he goes to the window and opens it. Later, when his daughter [Emma Stone] comes in the room and sees the open window with him gone, she races to first look at the ground far below with alarm. Then she looks up, and smiles. The end. We smile too. We’re smiling for the Keaton character who seems to have escaped as the Birdman – flying free of the mess on the ground. But what we’ve seen in truth, is a man jumping from the window of a multistory building. That is a dilemma…

When I wrote which side of the street?…, I suppose I hoped I’d be able to focus on Jeffrey Lieberman’s inappropriate and pompous rant on Medscape and avoid the British Psychological Society‘s report. But I can see I’m not going to get away with that. That is, in fact, one of the things that I find so hard about discussing this topic. No matter what I say about psychosis as I see it, I’m seen as taking a side and get hit from some other side as a <something not good>. Mention using neuroleptic medication and I’m a power hungry self-righteous ‘MDeity‘ who loves committing people. Say something about the recovery metaphor, or the down-side of diagnoses, or over-medication, and I’m suddenly a naive 60s type who thinks ‘all you need is love‘ who doesn’t understand trauma. Talk about psychotherapy, and I’m an unrepentant psychoanalyst who way overvalues "talk therapy" and "fanciful theories." At 73, I may have visited each of those pastures along the way, but it was a long time ago and I no longer remember even what they felt like. They didn’t fit for me because each of them relies on a notion of causality, and I don’t know what causes psychosis, or even if it’s a single thing. I tend to use the term Schizophrenia and its traditional subtypes in conversation, but even that has changed for me. Catatonia has been split off in a very helpful way. And there’s no question that in early days, I included cases I would now see as having obvious Manic-Depressive Illness. The ground shifts when you’re without the more solid signatures of my Internist days. But it is what it is.

• Understanding Psychosis and Schizophrenia
  The British Psychological Society
  Division of Clinical Psychology
  [full text on-line here]

  This report of the British Psychological Society mirrors a widespread reaction against a purely biomedical explanation for psychosis, for Schizophrenia. They propose the alternative possibility that it can be an adaptation to childhood trauma and abuse. They advocate access to psychotherapy for these patients and suggest using neuroleptic medications only when helpful or requested, not as a steady diet. "Many people find that ‘antipsychotic’ medication helps to make the experiences less frequent, intense or distressing. However, there is no evidence that it corrects an underlying biological abnormality. Recent evidence also suggests that it carries significant risks, particularly if taken long term." This report comes from the UK where offering talk therapy to psychotic patients is apparently mandated, but not really available. Something like that.

• Redefining Mental Illness
  by T. M. Luhrmann
  New York Times
  January 18, 2015

  Tanya Luhrman is an Anthropologist at Stanford. Among her books, Of Two Minds is a study of the transformation within psychiatry in the 1980s. In this New York Times piece, she reports favorably on the British Psychological Society’s report above, saying: "The implications are that social experience plays a significant role in who becomes mentally ill, when they fall ill and how their illness unfolds. We should view illness as caused not only by brain deficits but also by abuse, deprivation and inequality, which alter the way brains behave. Illness thus requires social interventions, not just pharmacological ones. One outcome of this rethinking could be that talk therapy will regain some of the importance it lost when the new diagnostic system was young. And we know how to do talk therapy. That doesn’t rule out medication: while there may be problems with the long-term use of antipsychotics, many people find them useful when their symptoms are severe…"

• Diagnosis: The View of the Psychiatric Association
  by Paul Summergrad
  New York Times
  January 27, 2015

  Luhrman had mentioned that the NIMH had abandoned the DSM-5 and instituted their RDoC Project. Paul Summergrad, current APA President, offered a short clarifying reply to her NYT piece: "Ms. Luhrmann notes approvingly that the National Institute of Mental Health, in beginning a program called Research Domain Criteria, determined that existing psychiatric diagnoses ‘were neither particularly useful nor accurate for understanding the brain, and would no longer be used to guide research.’ However, she does not mention a joint statement by the institute’s director, Dr. Tom Insel, and the former president of the American Psychiatric Association, Dr. Jeffrey Lieberman, which explained: ‘All medical disciplines advance through research progress in characterizing diseases and disorders. DSM-5 and RDoC [Research Domain Criteria] represent complementary, not competing, frameworks for this goal.’ Precisely."

• What Does the New York Times Have Against Psychiatry?
  by Jeffrey A. Lieberman
  Medscape
  February 18, 2015

The article about mental illness was an incredibly unscholarly, misinformed, confused — at worst, unhelpful, and at best, destructive — commentary that will add to the confusion about the diagnosis of mental illness, enhance the stigma, and may lead some patients to doubt the veracity of the diagnoses that they have been given and the treatments that they are receiving. Specifically, Dr Luhrmann was prompted to write this by a report that came from the British Psychological Society, which is a professional organization in the United Kingdom. This report, titled Understanding Psychosis and Schizophrenia, suggested that hearing voices and having feelings of paranoia were common experiences; that they commonly occur in the course of everyday life, particularly in the context of trauma, abuse, or deprivation, and that they shouldn’t be considered symptoms of mental illness and attached to diagnoses because that is only one way of viewing them. Viewing diagnoses as normative mental phenomena has relative advantages and disadvantages. This strikes me as preposterous. It is, at best, phenomenologic relativism, and at worst, simply conflating symptoms with a disorder or a disease… Viewing it this way is, in a way, challenging the veracity of diagnoses and giving people who have symptoms of a mental disorder, license to doubt that they may have an illness and need treatment…

Finally, when I read the article, disappointed and annoyed as I was, I tried to write a serious, responsible, and constructive letter to the editor, which I submitted within 24 hours. Seventy-two hours have elapsed since the article’s publication. I haven’t heard from the Times about their interest in publishing my response, so I assume they won’t publish it. The name that I publish under is my own. My credential is the Chairman of Psychiatry, Columbia University College of Physicians and Surgeons, one of the leading departments of psychiatry in the country, past president of the American Psychiatric Association, and author of the forthcoming book for the lay public called Shrinks: The Untold Story of Psychiatry. Assuming that my letter was not completely uninformed or incoherent, I would think that there would have been reason to accept it, given my credentials and the fact that I made a reasonable point. Let’s see if they print it. If they don’t, that adds further to my dismay over what I consider to be journalistically irresponsible behavior by this once-respected newspaper.

My own dog in this hunt has to do with an acquired pet peeve. I wrankle when people personify psychiatry as in "psychiatry thinks …" as if psychiatry is a unity all of one mind. I have the same reaction to "psychoanalysis thinks …" for that matter. Because what comes next is usually something I don’t think. But I try to keep my mouth shut because I can see why people do that. He purports to speak for all of us. But I sure don’t think all that Dr. Lieberman says in this piece. And I don’t think what the British Psychological Society or Tanya Luhrman think either, though their general recommendation of more judicious use of medication and access to "talk therapy" have always been part of my own thinking about these patients. Since I don’t know what causes psychosis, I would justify both recommendations on other grounds. There is little question in my mind that the neuroleptic medication can prevent relapse, and in a significant number of cases, that’s an important dilemma added into the mix.

When I arrived on the scene in psychiatry forty years ago, the psychoanalysts were entrenched in the seats of power much as the bio-psychiatrists are now. Some spoke from an arrogant position similar to that taken by Dr. Lieberman here. Even as an immigrating rookie from another specialty, I could sort of smell where that was headed. So it was back then that I learned about what happens when a paradigm flows way beyond its defensible boundaries. And like now, there was money involved – billing medical insurance for long but often optional psychotherapies. A sense of rightness clouded their vision and they missed many opportunities to become right-sized, attacking or becoming defensive when they should’ve been listening and adapting. Sounds familiar. Things were lost in the process.

• DSM-5: Caught between Mental Illness Stigma and Anti-Psychiatry Prejudice
  by Jeffrey A. Lieberman
  Scientific American
  May 20, 2013
• Anti-Psychiatry Prejudice? A response to Dr. Lieberman
  by Judy Stone
  Scientific American
  May 24, 2013

  "Conclusion: So many symptoms are now being medicalized, even absurdly, grief. It makes me wonder if there a DSM 5 diagnosis for someone who is self-serving, can’t accept criticism, and believes critics are prejudiced bigots? I was very disappointed to see Dr. Lieberman’s shallow, self-serving and evidence-free diatribe appear in Scientific American as a guest opinion. He failed to reveal important conflicts of interest. He made serious claims for which he presented no evidence. He has made thinly veiled personal attacks on his critics, without offering anything substantive to counter rationally…"

This morning’s thermometer says that we’re finally starting to thaw out down here a bit. Time for a real blog with graphs and numbers. Within the few years after the introduction of the Selective Serotonin Reuptake Inhibitor [SSRI] class of antidepressants, their association with suicidal ideation, suicide attempts, or suicides became the question of the hour based on case reports. There was an FDA Hearing in 1991 that didn’t find a signal sufficient for action. But by the next FDA Inquiry in 2004, meta-analysis of Clinical Trials was added to the case reports, and the FDA concluded that a signal justified adding a Black Box Warning to all antidepressants for adolescents, later extended to young adults. Throughout this period, investigators have also attempted to examine large practice databases to clarify this relationship.

Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database

by Carol Coupland, Trevor Hill, Richard Morriss, Antony Arthur, Michael Moore, and Julia Hippisley-Cox

British Medical Journal. 2015;350:h51.

[full text on-line]

Objective: To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression.

Design: Cohort study. Setting Patients registered with UK general practices contributing data to the QResearch database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012.

Exposures: Antidepressant class [tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants], dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables.

Main outcome measures: Suicide and attempted suicide or self harm during follow-up.

Results: During follow-up, 87.7% [n=209 476] of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days [interquartile range 79–590 days]. During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant [adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50], but the suicide rate was significantly increased during periods of treatment with other antidepressants [2.64, 1.74 to 3.99]. The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram [3.70, 2.00 to 6.84]. Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants [0.96, 0.87 to 1.08] compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants [1.80, 1.61 to 2.00]. The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine [1.85, 1.61 to 2.13], trazodone [1.73, 1.26 to 2.37], and mirtazapine [1.70, 1.44 to 2.02], and significantly reduced for amitriptyline [0.71, 0.59 to 0.85]. The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment.

Conclusion: Rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants. Mirtazapine, venlafaxine, and trazodone were associated with the highest rates of suicide and attempted suicide or self harm, but the number of suicide events was small leading to imprecise estimates. As this is an observational study the findings may reflect indication biases and residual confounding from severity of depression and differing characteristics of patients prescribed these drugs. The increased rates in the first 28 days of starting and stopping antidepressants emphasize the need for careful monitoring of patients during these periods.

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Supplementary Data: «link»

Protocol: «Safety of antidepressants in adults aged under 65: protocol for a cohort study using a large primary care database»

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The suicide rates in our study cohort [43 per 100 000 in men and 9 per 100 000 in women] are higher than those in the general population in England [three year average rates of 12.4 per 100 000 in men and 3.7 per 100 000 in women for 2010-12]. Larger differences than this might be expected since our rates are in patients with a diagnosis of depression rather than in the general population. Studies showing greater differences, however, have tended to be in secondary care settings, where patients have more severe depression. These results are consistent with those of our previous cohort study in older people with depression, which found that trazodone, mirtazapine, and venlafaxine were associated with the highest rates of attempted suicide or self harm in people aged 65 or more.

Conclusions:

This study has found that rates of suicide and self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic antidepressants, but were higher for the group of other antidepressant drugs, with mirtazapine, venlafaxine, and trazodone being associated with the highest risks. The number of suicide events was small so the results for suicide should be interpreted with caution. Rates tended to be highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment. These findings are of associations rather than causal effects and are particularly susceptible to confounding by indication, channelling bias, and residual confounding; further research is needed to confirm them. The results of this study indicate that patients taking antidepressant drugs should be carefully monitored, especially during early treatment with antidepressants and when stopping treatment.

Society holds our interactions with our customers – healthcare providers and payers – to a higher standard. And it should. Society expects our business to be conducted openly and transparently and in a way that does not create even a perception of inappropriate influence.
Deirdre Connelly speech January 2010

The quote is from a speech given by then newly appointed CEO of GlaxoSmithKline America, Deirdre Connelly, at the CBI 8th Annual Pharmaceutical Industry Compliance Congress in January 2010. It was a year and a half before GSK agreed to their $3 B settlement, "GSK agreed to plead guilty to a three-count criminal information, including two counts of introducing misbranded drugs, Paxil and Wellbutrin, into interstate commerce and one count of failing to report safety data about the drug Avandia to the Food and Drug Administration." And it was long before GSK’s ChinaGate scandal. When I read this speech back then, I was awed [see “so what went wrong?”…]. I guess I thought that either Connelly was the biggest sociopath on the planet, or she was an angel. I suspected the latter, but felt like I might be being the most gullible naive guy on the planet. I even hoped GSK would confess their sins [Study 329 for example]. But that didn’t happen. Deirdre Connelly, however, did happen. But now…

A Glaxo Exec Retires Amid Sales Slump and Reps Question a Bonus Program

Pharmalot: WSJ

By Ed Silverman

Feb 17, 2015

In the latest shift at GlaxoSmithKline, Deirdre Connelly, who has run the North American pharmaceuticals business for nearly six years, is retiring, according to a memo distributed yesterday to employees. She will be replaced by Jack Bailey, who most recently headed government affairs, managed markets and the vaccines business in the U.S., according to the memo. The move comes amid an ongoing reorganization at Glaxo, which has promised to cut expenses by $1.6 billion annually through 2017. The drug maker is struggling with declining sales in its key respiratory franchise and an overall sales drop in the U.S., which is its most important market and accounts for roughly one-third of companywide revenue.

“The U.S. healthcare environment is extremely challenging. We are making good progress with payers and early signals are encouraging, but there remains a lot to deliver,’ Abbas Hussain, the president of the Glaxo global pharmaceuticals business, wrote in the e-mail to employees. The memo was first reported by Bloomberg News. “With Jack heading the U.S. business, I feel confident that we have the right experience to steer us through the current environment and deliver our strategy. I’d also like to thank Deirdre for her leadership of the U.S. business these last six years – she is a great leader and a good friend. I’m incredibly grateful for everything she has done to reshape the U.S. business.”

The change comes after a management reshuffling last year in which Connelly, who arrived from Eli Lilly, began reporting to Abbas. Previously, she reported directly to Glaxo chief executive Andrew Witty, who has been under pressure to engineer a rebound not only from declining sales, but also a bribery scandal in China. During her tenure, Connelly, 54, attempted to steer Glaxo through a turbulent period. Last year, sales of respiratory medicines fell 18% in the U.S., due to both lower volume and price reductions. This reflected a 25% drop in Advair, one of its most important medicines [see here]. Two newer products have so far not generated anywhere near the needed sales levels. The Abbas e-mail also noted that Jorge Bartolome, a senior vice president for the respiratory  and medical centre unit, is leaving.

Besides the challenges of growing sales, however, Connelly also implemented a new and closely watched marketing program for sales reps called Patient First. Begun in 2011, this was designed in 2011, before the drug maker paid a $3 billion fine to the U.S. government to settle allegations of improper drug marketing to physicians, among other things. The program was seen as ground breaking because reps are not paid bonuses based on the volume of prescriptions written by doctors. Instead, bonuses have been based on product knowledge, business acumen and understanding needs of patients and physicians, which were assessed in written tests and simulations conducted by third parties. Supervisory observations are also used [details are here]… “The company put a lot of faith and effort in this system working and we are putting patients first,” says a Glaxo sales rep who asked not to be named. “But you wouldn’t go to a car salesman, who just sold some cars, and pay him based on his knowledge of the auto industry instead of commission. Salespeople are in it for sales and they’ve been seeing declines because the motivation isn’t there.”…

Doctors don’t need us to teach them how to practice medicine. But doctors do benefit from the very specific and extensive knowledge we have about our medicines and the conditions they treat. After all, it’s hard for health care providers to stay current with all the information available about thousands of medicines – and the new ones coming to market. When our GSK sales representatives talk with doctors, we require that they share the extensive knowledge they have about our drugs – including both who should, and importantly, who should not, take our medicines. This is something that my management team and I set as a fundamental requirement. Employees are trained to inform their customers when our products are not right for their patients. That is just one example of delivering value to the physician that is in the best interest of the patient…
Deirdre Connelly speech January 2010

Off-Label Promotion and Kickbacks: The civil settlement resolves claims set forth in a complaint filed by the United States alleging that, in addition to promoting the drugs Paxil and Wellbutrin for unapproved, non-covered uses, GSK also promoted its asthma drug, Advair, for first-line therapy for mild asthma patients even though it was not approved or medically appropriate under these circumstances. GSK also promoted Advair for chronic obstructive pulmonary disease with misleading claims as to the relevant treatment guidelines…

I may yet be naive and gullible, but I still think Deirdre Connelly was legit. If that’s true, her retirement brings up something fundamental. Can a publicly owned pharmaceutical company survive in a world where a drug isn’t hyped up and sold with aggressive and deceitful marketing? where it’s instead allowed to stand on its actual worth based on efficacy and safety? or will the push for profits, and the dreams of becoming a blockbuster drive the show? Whatever the case, let’s hope that her influence and policies have at least some sticking power. And if she applies to the FDA, let’s give her a long hard look…

Living in the South for a lifetime, one’s tolerance for this kind of cold is an undeveloped skill. People race to the grocery to stock up on things they usually don’t buy as if the Siege of Leningrad is beginning. Schools, clinics, and stores close in the morning [and regret it in the afternoon]. The worst part is the scorn and laughter coming from people who have emigrated here from the North as they watch us slide off the road because we don’t know how to negotiate the icy patches [and they actually own clothes appropriate for this kind of weather]. The dogs lobby constantly to go out, and then lobby constantly to come back in. And the woodpile, planned to be more than adequate for the season, grows smaller at an alarming rate.

Toward psychiatry as a ‘human’ science of mind. The case of depressive disorders in DSM-5

by Marco Castiglioni and Federico Laudisa

Department of Human Sciences, University of Milano-Bicocca, Milan, Italy

Frontiers in Psychology. 2014 5:1517.

[full text on-line]

The aim of this paper is to argue that a strictly reductionist approach to psychiatry represents a theoretical and clinical obstacle to a fruitful synthesis between neurobiological and sociocultural aspects of the sciences of mind. We examine the theoretical and practical motivations underlying this approach, by analyzing the case of depressive disorders, as defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM], and the related removal of the “bereavement exclusion clause.” We first explore the claim that DSM is atheoretical, observing that, far from being atheoretical, DSM adopts an implicit, biologically inspired view of the mind; we show that such a view leads to a sort of circularity in the definition of depressive disorders, in which psychopharmacology seems to play a key role. We then turn to further problems deriving from this position, analyzing the issue of placebo effects in the treatment of depressive disorders and the philosophical question of normative preconditions for psychopathological diagnosis. Finally, we address the issue of subjectivity, which, together with the related aspect of the subject’s relational context, appears to be crucial to any scientific theorizing about mental disorders, despite DSM’s attempt to exclude it. Our defense of a non-reductionist view of mental disorders, however, does not imply that we endorse any sort of metaphysical dualism, or anti-diagnostic or anti-psychiatric positions. On the contrary, we argue that the adoption of a reductionist position actually undermines the theoretical and clinical accuracy in explaining depressive disorders…

But I don’t really buy my it’s too cold to think about it excuse for having nothing to say about this paper. I thought of some lines from my oft-quoted poet:

It has all already been said "Once or twice, or several times, by men whom one cannot hope to emulate." I’ve thought all of the things in this paper in one form or another for twenty-plus years. But it’s more than that, because I’ve worked up a full head of steam about these matters many times in the last several years. I hope my torpor reflects something more general. The DSM-5, for all the hoopla, was a non-event. It’s not even a DSM-IV on steroids. It’s a DSM-IV with some quirky changes. Maybe [fingers crossed] it’s back to being a code book where it belongs [and a not-very-good code book at that]. Now they’re publishing a version for patients and the lay public [maybe an attempt to stir up some interest somewhere? amywhere?]. But other than that, it’s not much mentioned.