incremental marker…

Posted on Wednesday 24 June 2015

I suppose most Southerners have something to say about  the goings on after the Charleston shooting and all the media attention about the battle flag. As a boy growing up in Chattanooga Tennessee literally in an area peppered with cannons and Civil War Monuments, I had no idea that the Civil War was even about slavery. That seems as outrageous to my to say as it must be to read. When I hear other people say things like that, I hear it as possibly reconstructing history, but for me to say otherwise would be a lie. My Dad was from an Italian immigrant family; grew up in a Northern coal mining town on the wrong side of prejudice; and came South on a football scholarship. My mother was from rural Georgia – a vaudeville family – and a soft spoken do-gooder somewhere to the left of anyone else in Tennessee I ever met. We were raised to sit in the back of the bus and go out of our way to be respectful to black people. It was odd, because I never met anyone else that said that, But for that matter, I can’t recall anyone actually talking about segregation much in those times. It was just part of the fabric of life. And it was disconnected from the stories of chivalry and honor – and that flag.

With that kind of background, I was an early convert when the Civil Rights Movement got started, even in high school ["class of sixty, best in Dixie"]. And by 1966, my new wife and I were veteran marchers and picketers, but the flag hadn’t changed in my mind. We took a camping trip from our apartment in Memphis in the summer of 1966, and that’s when the flag came into things [selective memory…]:
Back in the summer of 66, my young wife and I took a camping trip down the Mississippi Delta from Memphis where I was finishing Medical School. We wanted to take some Jim Crow pictures to preserve what it had been like there – thinking that we were finally on the downhill leg of the Civil Rights Movement, and people might try to forget. In the course of our travels, we saw a sign to Ruleville Mississippi – a place we’d heard of from watching the Democratic Convention when the Mississippi Freedom Democrat Party tried to be seated. Their most eloquent spokesperson was Fannie Lou Hamer from Ruleville, a tiny town in the heart of the cotton fields that covered the Delta in those days. [Notice that President Johnson cut her off of national television during her speech]:

As we drove into town, we knew we were in the right place for our photographs. There was a Dairy Queen on the way into town with a strange addition built onto the front of it with a large picture window. On the back wall was a huge Confederate Battle Flag tacked up on the wall. The sign outside said, White Citizens Council Annex, Private Club. So we drove through town, photographing the "white" and "colored" signs that had defined the segregated South of our childhood. My wife was driving as I clicked away. She circled back, determined to get a picture of the White Citizens Council Dairy Queen. We parked nearby, but I noticed that the same two-tone blue 1956 Ford that had been following us earlier pulled up right behind. I also notice that there was a shotgun mounted vertically between the two guys in the front seat.

So we drove on, forgoing our photo-op, followed by the two-tone blue Ford. When we reached the Sunflower County Line, it mercifully turned around. When we finally stopped for gas and gathered some composure, we started wondering how they knew we were "foreigners." There, on the rear bumper of my car was the answer – a black and white A.C.L.U. bumper sticker that simply said, "JUSTICE." Our pictures didn’t survive the 50 years in between, but the memories did.
It seems peculiar to me that, until then, I hadn’t connected that flag with racism and it hadn’t solidly sunk in that the Civil War was indeed about slavery. How I could’ve been so involved in "the Movement" and yet be oblivious to how my childhood version of history actually went together with it is now beyond my comprehension. But seeing that flag in the Ruleville Mississippi White Citizens Council Dairy Queen picture window did the trick.

In the mid-1980s, my teenaged daughter and a friend announced that they were going to "a march." They’d heard us and our friends tell our epic tales of our marching days, and decided they wanted to get in on the action. There was a poor rural county north of Atlanta, all white, that was "racist." A school teacher had organized a small MLK day parade, that had been broken up by "the Klan." The next week, Hosea Williams, a local Civil Rights leader took a bus filled with students from the Black Atlanta colleges, and the same thing happened. So he got serious, and mobilized a big march. Meet at the King Center and ride buses up to this town. So the four of us showed up along with 20,000+ other Atlantans. They finally got all the City buses there and every church bus in town, and off we went. There were more marchers than people in that whole county. The comic relief was this armada of buses stopping on the Interstate for a 20,000 person strong pee break. Men on the port side at the fence, women in the woods on the starboard side. The county was overwhelmed by the invading horde [now a bustling suburb with McMansions in what used to be those empty fields].

But the point is that back then, the sides of the highway were lined with people, mouths agape, some of whom had denim jackets with Klan logos, waving those battle flags and throwing snowballs from what was left of a rare Georgia snowstorm. When we got back to the buses, we were among a few hundred people that didn’t get on a bus. By then, it was night, and we were gathered on an overpass. And here came the pickup trucks with battle flags mounted on the beds and people leaning out the windows twirling chains and hurling epithets. They had been soundly defeated and they were plenty mad. After about 45 very long minutes [during which I questioned my parental judgement], the State Troopers discovered us and herded us into a parking lot, calling for more buses. As fate would have it, our bus broke down as we got off  the Interstate in Atlanta, and we had to walk the full length of "Sweet Auburn Avenue" – the heart of the black Atlanta "club scene" with two very cute blond teens who were quite the objects of interest on this particular Saturday night. A memorable day – snowballs early and cat-calls late. But if I had any remaining romantic attachments to that flag, 45 minutes on that overpass put an end to them for good.

In 2001, then Georgia Governor Roy Barnes changed the Georgia flag, a leftover from segregationist days. It actually probably cost him being re-elected [now I read our "new flag" was a confederate flag too. Who knew?]. But whatever, I feel kind of proud that the Southern States are moving towards finally removing those anachronistic symbols. Whatever they meant, or now mean, we can do without them:

I hate what happened to get things moving, that senseless shooting. But I didn’t know I’d live long enough to see this happen – no matter the stimulus. I mentioned that my two best friends died within a week of each other a little over a year ago [in memory…]. They were veterans of those days too, much more than I was. I’m just sorry they didn’t get to see this incremental marker of the change that was such an important goal in their lives. Change is so slow, and you never know just when or how it’s going to happen…
Mickey @ 11:08 PM

down pat…

Posted on Tuesday 23 June 2015

This Age of Meta-Analyses in matters of the psyche is poking holes in some broadly held paradigms, nowhere more apparent than those relating to the notion of the monolithic Major Depressive Disorder. The efficacy and safety of the SSRIs are being widely re-considered. The DSM-5 Field Trials made an assault on the bedrock reliability that vaulted Major Depressive Disorder into being in the first place:

[kappa values in the DSM Field Trials]

Now we have this Meta-Analysis of one of the mainstays of treatment, Cognitive Behavior Therapy:
by Tom J. Johnsen and Oddgeir Friborg
Psychological Bulletin. 2015 May 11. [Epub ahead of print]

A meta-analysis examining temporal changes [time trends] in the effects of cognitive behavioral therapy [CBT] as a treatment for unipolar depression was conducted. A comprehensive search of psychotherapy trials yielded 70 eligible studies from 1977 to 2014. Effect sizes [ES] were quantified as Hedge’s g based on the Beck Depression Inventory [BDI] and the Hamilton Rating Scale for Depression [HRSD]. Rates of remission were also registered. The publication year of each study was examined as a linear metaregression predictor of ES, and as part of a 2-way interaction with other moderators [Year x Moderator]. The average ES of the BDI was 1.58 [95% CI 1.43, 1.74], and 1.69 for the HRSD [95% CI 1.48, 1.89]. Subgroup analyses revealed that women profited more from therapy than did men [p < .05]. Experienced psychologists [g = 1.55] achieved better results [p < .01] than less experienced student therapists [g = 0.98]. The metaregressions examining the temporal trends indicated that the effects of CBT have declined linearly and steadily since its introduction, as measured by patients’ self-reports [the BDI, p < .001], clinicians’ ratings [the HRSD, p < .01] and rates of remission [p < .01]. Subgroup analyses confirmed that the declining trend was present in both within-group [pre/post] designs [p < .01] and controlled trial designs [p = .02]. Thus, modern CBT clinical trials seemingly provided less relief from depressive symptoms as compared with the seminal trials. Potential causes and possible implications for future studies are discussed.

In-so-far as I can see, this was a well conducted and very thorough analysis. The "funnel plots" suggest that there’s some publication bias, but it’s not a lot [see paper]. The article has  the expectable section at the end speculating on the "why" of their findings which I’ll leave for your own perusal since it’s available on-line. It seems to cover the usual suspects and does acknowledge the paradox that one would think an intervention like this ought to improve with practice. I am not a CBTer myself, but I am familiar with it from reading Beck’s works and several seminars, though I didn’t "do it" in a formal way. Certainly, the idea of depressive cognition was incorporated back in the day by most all  psychotherapists of any ilk.

Rather than speculate and obsess on the why of a waning response to CBT or the why of the plummeting kappa in the DSM Field Trials [or for that matter the why of the Placebo changes described by Kirsch [first rate madness…] or the other challenges to the reported efficacy of SSRI/SNRI antidepressants], I think I’ll just add this to the already too long list of things that discredit the idea that one can be very scientific with a category that elevates dysphoric emotion to the level of a disease entity and offers simple generic solutions. Looking at the last several posts [about Collaborative Care], there’s a whole system being built around some psychiatrist reviewing cases with a Care Manager sight unseen and making pronouncements about a treatment plan that prescribes CBT and/or Drugs to treat this obviously changing and heterogeneous category called Major Depressive Disorder.

People are moving ahead as if we have this business of treating MDD down pat. We don’t and won’t. As Ed Shorter put it in Before Prozac, "Bottom Line: Major Depression doesn’t exist in Nature. A political process in psychiatry created it." Frankly, I’n impressed that CBT has held up as well as it has…
Mickey @ 4:13 PM

added for completeness…

Posted on Monday 22 June 2015

In the course of things, I ran across this report which seems relevant to the recent discussion of the Collaborative Care model [and likely has as much to do with its construction as any other factor mentioned]:

Mickey @ 6:39 PM

comment on a comment…

Posted on Monday 22 June 2015

This comment on the last post [a requiem in the key of infrequent interaction…] might clarify some of my visceral aversion to the discussions of Collaborative and/or Integrative Care.

    I don’t think the APA leadership support of this is financially motivated. I think it is ideologically motivated. Which in this case is worse, because if they had the financial interests of the group in mind [not to mention basic professionalism and the interest of individual patients] they wouldn’t support it. Lieberman, who posted the first video about this from APA, was a big fan of carving out a role for psychiatry under ACA because he was thoroughly committed to ACA politically and the idea of treating populations rather than patients.
I’ve embedded two short APA videos on the topic: the one from Jeffrey Lieberman mentioned above and one from Paul Summergrad a year later. In addition, I’ve included more than you’ll want to look at from other APA sources:
APA: Collaborative Care

This is a population model that incorporates various instruments [screening, PHQ-9, etc] along the way. It’s built on the naive notion that one can treat mental health problems with a prescription pad and/or CBT. It reminds me of a graphic I drew when I first started blogging about psychiatry and mental health matters a number of years ago. I drew it meaning to be facetious, but maybe I should have applied for a patent…

Mickey @ 4:44 PM

a requiem in the key of infrequent interaction…

Posted on Saturday 20 June 2015

The goals of Integrated Care: Working at the Interface of Primary Care and Behavioral Health are to educate psychiatrists about the fundamental shift underway in health care and to prepare them to be successful and effective in the new health care arena. The passage and implementation of the Patient Protection and Affordable Care Act presents an opportunity for newly insured patients and for funding models of integrated care, enabling psychiatrists to have a more significant population-level impact…
Edited by Lori E. Raney, M.D.

The integration of physical and mental health care is an important aspect of the Medicaid health home model. Collaborative care programs are one approach to integration in which primary care providers, care managers, and psychiatric consultants work together to provide care and monitor patients’ progress. These programs have been shown to be both clinically-effective and cost-effective for a variety of mental health conditions, in a variety of settings, using several different payment mechanisms. This brief highlights the collaborative care model as one approach to implementing integrated care under the Medicaid health homes authority.

"… developing innovative integrated care models and translating research on evidence-based behavioral health interventions into effective clinical and public health practice." I admit to an involuntary visceral aversion to this kind of jargon filled patter. And it seems to be the preferred rhetoric in a lot of the literature on Collaborative Care [AKA Integrative Care] that apparently looms as a vision of the future for psychiatry [two versions…, my say…, not directly seeing the patients…]. It’s obviously a big push item from SAMHSA, APA, Medicare, Medicaid, ACA, Managed Care, etc. This, from one of the epicenters at the University of Washington:
Collaborative Care is a specific type of integrated care developed at the University of Washington that treats common mental health conditions such as depression and anxiety that require systematic follow-up due to their persistent nature. Based on principles of effective chronic illness care, Collaborative Care focuses on defined patient populations tracked in a registry, measurement-based practice and treatment to target. Trained primary care providers and embedded behavioral health professionals provide evidence-based medication or psychosocial treatments, supported by regular psychiatric case consultation and treatment adjustment for patients who are not improving as expected.

Collaborative Care originated in a research culture and has now been tested in more than 80 randomized controlled trials in the US and abroad. Several recent meta-analyses make it clear that Collaborative Care consistently improves on care as usual. It leads to better patient outcomes, better patient and provider satisfaction, improved functioning, and reductions in health care costs, achieving the Triple Aim of health care reform. Collaborative Care necessitates a practice change on multiple levels and is nothing short of a new way to practice medicine, but it works. The bottom line is that patients get better.
Previously, I posted two versions… of the Collaborative Care model, one from the American Psychiatric Association and one from a paper in JAMA [ Health Reform, Research Pave Way for Collaborative Care for Mental Illness ]. This one is from the AIMS Center at the University of Washington:

[click image for description]

Obviously, from all the noise from the APA higher-ups and PsychiatricNews, the APA had its hand in this story. Essentially, it’s a step beyond the last sell out in that psychiatrists have a sit down with the Care Manager and discuss cases of patients they’ve never seen, making suggestions to be passed on to others. The only reason that the psychiatrist is there is that they’ve figured out that the primary care docs know nothing of mental illness and prescribe very badly. So we’re there to prescribe better – only to do it blindfolded – formerly known as malpractice. It’s an absurd scheme that can only produce psychiatrists that end up as in the dark as the primary care doctors they advise via proxy. So it’s at least clear why the rhetoric is so jargon filled – take away the jargon and there’s nothing there. My advice? Insert No Roles where it says New Roles.

The great irony of this legacy passed on to us from the PHARMA tarnished KOLs who sold out psychiatry long ago is that it forces anyone participating in it to do the very thing that everyone is complaining about – see medication as the first line treatment of mental illness and overprescribe. To even amplify the  irony, this model is essentially supported and encouraged by the people who criticize the bio-bio-bio models the most [see the rise and ??? of the guild…]. The KOLs and PHARMAs of the decades bracketing the century mark succeeded in reducing psychiatry to pill-pushing for their profit and this is what they’ve passed along to us – now encoded as Collaborative Care. What other Behavioral Health Clinicians haven’t quite figured out is that they are on a dotted line too, and are already feeling their future dwindling along with psychiatry and headed for a similar fate. Unfortunately, for all concerned, all of this actually hinges on the business-fication of the word "Care," and is unlikely to change until society rediscovers other meanings of the word. Like the bumper sticker in the 1980s prophetically said, "Managed Care is Neither!"

Here are the abstracts of the reliable meta-analyses so far:
The Cochrane Collaboration
by Janine Archer, Peter Bower, Simon Gilbody, Karina Lovell, David Richards, Linda Gask, Chris Dickens, and Peter Coventry
17 OCT 2012

Background: Common mental health problems, such as depression and anxiety, are estimated to affect up to 15% of the UK population at any one time, and health care systems worldwide need to implement interventions to reduce the impact and burden of these conditions. Collaborative care is a complex intervention based on chronic disease management models that may be effective in the management of these common mental health problems.
Objectives: To assess the effectiveness of collaborative care for patients with depression or anxiety.
Search methods: We searched the following databases to February 2012: The Cochrane Collaboration Depression, Anxiety and Neurosis Group [CCDAN] trials registers [CCDANCTR-References and CCDANCTR-Studies] which include relevant randomised controlled trials [RCTs] from MEDLINE [1950 to present], EMBASE [1974 to present], PsycINFO [1967 to present] and the Cochrane Central Register of Controlled Trials [CENTRAL, all years]; the World Health Organization [WHO] trials portal [ICTRP];; and CINAHL [to November 2010 only]. We screened the reference lists of reports of all included studies and published systematic reviews for reports of additional studies. Selection criteria: Randomised controlled trials [RCTs] of collaborative care for participants of all ages with depression or anxiety.
Data collection and analysis: Two independent researchers extracted data using a standardised data extraction sheet. Two independent researchers made ‘Risk of bias’ assessments using criteria from The Cochrane Collaboration. We combined continuous measures of outcome using standardised mean differences [SMDs] with 95% confidence intervals [CIs]. We combined dichotomous measures using risk ratios [RRs] with 95% CIs. Sensitivity analyses tested the robustness of the results.
Main results: We included seventy-nine RCTs [including 90 relevant comparisons] involving 24,308 participants in the review. Studies varied in terms of risk of bias. The results of primary analyses demonstrated significantly greater improvement in depression outcomes for adults with depression treated with the collaborative care model in the short-term [SMD -0.34, 95% CI -0.41 to -0.27; RR 1.32, 95% CI 1.22 to 1.43], medium-term [SMD -0.28, 95% CI -0.41 to -0.15; RR 1.31, 95% CI 1.17 to 1.48], and long-term [SMD -0.35, 95% CI -0.46 to -0.24; RR 1.29, 95% CI 1.18 to 1.41]. However, these significant benefits were not demonstrated into the very long-term [RR 1.12, 95% CI 0.98 to 1.27]. The results also demonstrated significantly greater improvement in anxiety outcomes for adults with anxiety treated with the collaborative care model in the short-term [SMD -0.30, 95% CI -0.44 to -0.17; RR 1.50, 95% CI 1.21 to 1.87], medium-term [SMD -0.33, 95% CI -0.47 to -0.19; RR 1.41, 95% CI 1.18 to 1.69], and long-term [SMD -0.20, 95% CI -0.34 to -0.06; RR 1.26, 95% CI 1.11 to 1.42]. No comparisons examined the effects of the intervention on anxiety outcomes in the very long-term. There was evidence of benefit in secondary outcomes including medication use, mental health quality of life, and patient satisfaction, although there was less evidence of benefit in physical quality of life.
Authors’ conclusions: Collaborative care is associated with significant improvement in depression and anxiety outcomes compared with usual care, and represents a useful addition to clinical pathways for adult patients with depression and anxiety.
The Cochrane Collaboration.
by Siobhan Reilly, Claire Planner, Linda Gask, Mark Hann, Sarah Knowles, Benjamin Druss, and Helen Lester
4 NOV 2013

Background: Collaborative care for severe mental illness [SMI] is a community-based intervention, which typically consists of a number of components. The intervention aims to improve the physical and/or mental health care of individuals with SMI.
Objectives: To assess the effectiveness of collaborative care approaches in comparison with standard care for people with SMI who are living in the community. The primary outcome of interest was psychiatric admissions.
Search methods: We searched the Cochrane Schizophrenia Group Specialised register in April 2011. The register is compiled from systematic searches of major databases, handsearches of relevant journals and conference proceedings. We also contacted 51 experts in the field of SMI and collaborative care.
Selection criteria: Randomised controlled trials [RCTs] described as collaborative care by the trialists comparing any form of collaborative care with ‘standard care’ for adults [18+ years] living in the community with a diagnosis of SMI, defined as schizophrenia or other types of schizophrenia-like psychosis [e.g. schizophreniform and schizoaffective disorders], bipolar affective disorder or other types of psychosis.
Data collection and analysis: Two review authors worked independently to extract and quality assess data. For dichotomous data, we calculated the risk ratio [RR] with 95% confidence intervals [CIs] and we calculated mean differences [MD] with 95% CIs for continuous data. Risk of bias was assessed.
Main results: We included one RCT [306 participants; US veterans with bipolar disorder I or II] in this review. We did not find any trials meeting our inclusion criteria that included people with schizophrenia. The trial provided data for one comparison: collaborative care versus standard care. All results are ‘low or very low quality evidence’.Data indicated that collaborative care reduced psychiatric admissions at year two in comparison to standard care [n = 306, 1 RCT, RR 0.75, 95% CI 0.57 to 0.99].The sensitivity analysis showed that the proportion of participants psychiatrically hospitalised was lower in the intervention group than the standard care group in year three: 28% compared to 38% [n = 330, 1 RCT, RR 0.72, 95% CI 0.53 to 0.99].In comparison to the standard care group, collaborative care significantly improved the Mental Health Component [MHC] of quality of life at the three-year follow-up, [n = 306, 1 RCT, MD 3.50, 95% CI 1.80 to 5.20]. The Physical Health Component [PHC] of the quality of life measure at the three-year follow-up did not differ significantly between groups [n = 306, 1 RCT, MD 0.50, 95% CI 0.91 to 1.91].Direct intervention [all-treatment] costs of collaborative care at the three-year follow-up did not differ significantly from standard care [n = 306, 1 RCT, MD -$2981.00, 95% CI $16934.93 to $10972.93]. The proportion of participants leaving the study early did not differ significantly between groups [n = 306, 1 RCT, RR 1.71, 95% CI 0.77 to 3.79]. There is no trial-based information regarding the effect of collaborative care for people with schizophrenia.No statistically significant differences were found between groups for number of deaths by suicide at three years [n = 330, 1 RCT, RR 0.34, 95% CI 0.01 to 8.32], or the number of participants that died from all other causes at three years [n = 330, 1 RCT, RR 1.54, 95% CI 0.65 to 3.66].
Authors’ conclusions: The review did not identify any studies relevant to care of people with schizophrenia and hence there is no evidence available to determine if collaborative care is effective for people suffering from schizophrenia or schizophreniform disorders. There was however one trial at high risk of bias that suggests that collaborative care for US veterans with bipolar disorder may reduce psychiatric admissions at two years and improves quality of life [mental health component] at three years, however, on its own it is not sufficient for us to make any recommendations regarding its effectiveness. More large, well designed, conducted and reported trials are required before any clinical or policy making decisions can be made.
Mickey @ 3:28 PM

the Age of the Decepticons…

Posted on Thursday 18 June 2015

The Treatment for Adolescents with Depression Study [TADS] was an NIMH funded clinical trial including 439 adolescents that ran from September 1998 though March 2004. The study compared Placebo [PBO], Prozac [FLX], Cognitive Behavior Therapy [CBT], and Prozac+Cognitive Behavior Therapy [COMBO] for 12 weeks in a blinded RCT. But that’s not all folks.  They then broke the blind and followed the subjects for another 24 weeks. PBO non-responders could then choose FLX, CBT, or COMBO:
by March JS, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, and Severe J
Archives of General Psychiatry. 2007 64[10]:1132-1143.

CONCLUSIONS: In adolescents with moderate to severe depression, treatment with fluoxetine alone or in combination with CBT accelerates the response. Adding CBT to medication enhances the safety of medication. Taking benefits and harms into account, combined treatment appears superior to either monotherapy as a treatment for major depression in adolescents.
by Benedetto Vitiello, Susan Silva, Paul Rohde, Christopher Kratochvil, Betsy Kennard, Mark Reinecke, Taryn Mayes, Kelly Posner, Diane E. May, and John S. March.
Journal of Clinical Psychiatry. 2009 70[5]: 741–747.

RESULTS: Forty-four patients [10.0%] had at least 1 suicidal event [no suicide occurred]. Events occurred 0.4 to 31.1 weeks [mean +/- SD = 11.9 +/- 8.2] after starting TADS treatment, with no difference in event timing for patients receiving medication versus those not receiving medication. Severity of self-rated pretreatment suicidal ideation [Suicidal Ideation Questionnaire adapted for adolescents score > or = 31] and depressive symptoms [Reynolds Adolescent Depression Scale score > or = 91] predicted occurrence of suicidal events during treatment [P < .05]. Patients with suicidal events were on average still moderately ill prior to the event [mean +/- SD Clinical Global Impressions-Severity of Illness scale score = 4.0 +/- 1.3] and only minimally improved [mean +/- SD Clinical Global Impressions-Improvement scale score = 3.2 +/- 1.1]. Events were not preceded by increased irritability, akathisia, sleep disturbance, or manic signs. Specific interpersonal stressors were identified in 73% of cases [N = 44]. Of the events, 55% [N = 24] resulted in overnight hospitalization.
CONCLUSIONS: Most suicidal events occurred in the context of persistent depression and insufficient improvement without evidence of medication-induced behavioral activation as a precursor. Severity of self-rated suicidal ideation and depressive symptoms predicted emergence of suicidality during treatment. Risk for suicidal events did not decrease after the first month of treatment, suggesting the need for careful clinical monitoring for several months after starting treatment.
Among the bizarre misrepresentations in Clinical Trials of psychiatric drugs during the Age of the Decepticons, this one may take the grand prize. The full story is covered in significant I… and significant II…, but here’s the punchline:

« truncated » · « recolored » · « click for original »

This is figure 1 from that last paper. A more truthful version of the legend would read:

As much as I appreciate someone finally mentioning psychological factors ["Most suicidal events occurred in the context of persistent depression and insufficient improvement without evidence of medication-induced behavioral activation as a precursor"] as even existing, they’re just trying to dissuade us from looking at figure 1 and seeing what it actually says: Prozac caused suicidality in a significant portion of adolescents in the NIMH funded TADS trial. No statistical tests needed to see that. And what person with suicidal thinking or attempts ever didn’t have an explanation?

This disconnect between the narrative and the data came to my attention from the posts by David Healy [Coincidence a fine thing] and Robert Whitaker [The Real Suicide Data from the TADS Study Comes to Light]. I ran across them vetting an absurd paper by statistician, Robert Gibbons [Suicidal Thoughts and Behavior With Antidepressant TreatmentReanalysis of the Randomized Placebo-Controlled Studies of Fluoxetine and Venlafaxine], in one of his many attacks on the Black Box Warnings [a warning that the TADS trial actually supports]. Both Healy and Whitaker [and I] attribute the discovery of this damning chart amid the din of TADS papers to Swedish Investigator Göran Högberg [his comments from our 2012 email conversation are in my significant I… post].

So finally, Högberg‘s finding makes it into the medical literature [years after the patent ran out]:
by Högberg, Göran | Antonuccio, David O. | Healy, David.
International Journal of Risk & Safety in Medicine. 2015 27[2]:85-91.

Completed suicides are a major cause of death in adolescents in Sweden. Forensic analysis of completed suicides in children and adolescents shows there is one completed suicide per 1000 children taking a selective serotonin re-uptake inhibitor [SSRI]. In order to elucidate these events we undertook a study of the results and reporting of suicidal events in the Treatment of Adolescents with Depression Study [TADS]. We conclude that a major, albeit underreported, finding in the TADS was the significant increase of suicidal events in the adolescents on antidepressant medication in comparison to the group on placebo medication. The proportions of suicidal events were 11% and 2.7% respectively. This increased risk of suicidal events might be related to the high incidence of medication with an SSRI in the group of completed suicides among Swedish adolescents:
« from Högberg et al’s version » · « recolored »
DecepticonIt’s years late, and it’s softly presented, but it’s still something of a breakthrough. It’s what we’re hoping for from Data Transparency, but they didn’t have to petition for the data or jump through any hoops as it was just hiding there in plain sight. And it’s a republication of a deceptively presented NIMH funded study, setting the record straight. It may seem frivolous to name these studies that distort the Clinical Trial findings after characters from the SciFi Transformer comics and movies, but the term Decepticons just fits them to a tee [deceptive icons]. The TADS trial produced some twenty publications, and is widely quoted recommending SSRI treatment for depressed adolescents. It’s also used in most arguments against the Black Box Warning, as in the paper quoted above. Perhaps NIMH Director Insel might grace us with a blog on Högberg’s paper?
Mickey @ 4:31 PM

the business of doing business….

Posted on Wednesday 17 June 2015

In looking at the history of psychiatry, 1980 marks a radical change with the introduction of the DSM-III. But that was hardly the only thing happening in 1980, not by a long shot. Probably the most remarkable event was the election of Ronald Reagan which marked a dramatic change in our way of doing capitalism – the unregulated free-market way. 1980 is where a lot of graphs begin – like the rise of wealth inequity or our separating from the rest of the world with medical costs [in spite of no gain]. Reagan’s deregulation was sustained and defended by his Federal Reserve Chairman, Alan Greenspan, who artfully controlled our free economy by manipulating interest rates from 1987 until retiring in 2005, just as the housing market began its free-fall, ushering in the Great Recession in 2008:

Probably the most perceptive observer of human behavior of the era was actually an economist at Yale, Robert Shiller, who found a way to quantitate the value of real estate, the Case Shiller Index. In 2000 he published a book, Irrational Exuberance, that predicted what would happen when the real estate "bubble" finally "burst." His title came from a speech by Alan Greenspan explaining away the earlier "DotCom bubble" as an anomoly. In Shiller’s Behavioral Economics, it was a an example of a natural exception to the Supply/Demand economic principle – a runaway financial market doomed to collapse – something like the Gold Rush. The Housing Market did indeed crash in spades, just as he predicted, bringing the economy down with it:

We watched as huge companies whose main business was the business of doing business fell one after another as the ramifications of their Irrational Exuberance spread across the country and unemployment soared. 2008 closed the parentheses opened in 1980, and it happened in psychiatry then as well when Senator Grassley exposed a list of prominent academic psychiatrists who were participating in and profiting from a psychopharmacology bubble of sorts. It didn’t crash like the overall economy, but it at least lost some of its magical aura. The drug companies had mirrored the general trend of becoming increasingly into the business of doing business, and it’s still happening:
Pharmalot: WSJ
By Ed Silverman
June 16, 2015

For the past several years, the pharmaceutical industry has been relying on a model that sometimes resembles Hollywood studios. Rather than use their resources to build every medicine from scratch, the biggest drug makers increasingly look outside their own labs to buy a company or license a compound and then use their financial, regulatory and marketing muscle in hopes of creating a hit.
Ed tells it in a softer way than I would. These are companies whose main business is the business of doing business. Like Enron, AIG, Countrywide, and countless others, they’re in their corporate offices and not in their laboratories or manufacturing plants. They’re disconnected from the essence of their purpose. And unfortunately, they’re not the only piece of medical pie where that has happened:
So how is that working out? A new analysis says not so well, at least for most companies. With few exceptions, most drug makers did not end up using their capital efficiently to make acquisitions between 2004 and 2014, according to the analysis by the McKinsey consulting firm. Similarly, few drug makers succeeded in forging licensing deals that generated blockbuster products. Put another way: most drug makers had low hit rates. “Overall, it seems few companies excel at sourcing innovation externally,” the consultants wrote in Nature Reviews Drug Discovery…

To be sure, there were success stories. For example, there was the $11 billion that Gilead Sciences paid to acquire Pharmasset and its hepatitis C compounds. As for licensing, the consultants pointed to a pair of deals in which Johnson & Johnson  licensed the Xarelto bloodthinner from Bayer and the Imbruvica cancer treatment from Pharmacyclics. But only two drug makers – Roche and J&J – ranked highly in both categories.

“It’s really hard to be successful at both M&A and licensing,” says Myoung Cha, a partner in the medical products practice at McKinsey. “There are few companies that seem to be consistently good. Overall, there’s a huge spread in performance in efficiency, at least among the largest companies… And licensing looks very similar to venture capital investment. One or two great deals can make all the difference.”

In fact, the analysis found that few drug makers were able to license one or more blockbuster medicines over that 10-year period, despite a large number of deals. And most of the blockbuster deals – seven out of 10 – involved late-stage licenses, which suggests that many of the higher-quality molecules were more expensive to source, according to the consultants.

So what does this mean for the notion that external sourcing will save the day and help the pharmaceutical industry reinvent itself? “Many companies are trying to make large pushes to external sourcing,” says Cha. “And many say it’s a great way to augment the pipeline. I would also say it’s not a panacea for building a strong pipeline. Companies really need to think hard about where to generate return for dollars invested – internal or external discovery. External sourcing is simply not a capability that every company has equally.”
Like any good psychotherapist, Robert Shiller saw a piece of human behavior in economic systems that made little sense, and he figured out how to both document it and make predictions based on what he saw. Part of that paradigm involves making the change from being a company that researches, developes, tests, and then markets medications into a company that uses their financial, regulatory and marketing muscle in hopes of creating a hit – the business of doing business.

But there’s a point here beyond my diatribe about corporate greed. PHARMA is a protected industry. The Approval process eg only two positive studies; the generous patent life; the patent extension options; allowing Direct-to-Consumer Advertising; the absence of strong price regulation; colluding with keeping their data hidden; all are among the many ways we reward the pharmaceutical industry for their research and development of new medical treatments. They get special concessions as payback for their R&D efforts.

If they’re not doing Research and Development and are spending their time on the business of doing business and doing a Gilliad [gagging price gouging on a captive audience via patent protection], why should we continue to give them special treatment? Why, indeed?…
Mickey @ 6:37 PM

darwin 101…

Posted on Tuesday 16 June 2015

Five years ago, I was trying to explore the factors behind our medical schools tolerating all of the Academic Psychiatrists that were so allied with the pharmaceutical industries. I could find no way to quantitate how much money was flowing into the Universities from industry. But I could find out about NIMH money,  so I compiled the amounts coming to the University where I was on the faculty, Emory University. The PHARMA money was much more discretionary, but I thought the NIMH money might at least give us a sense of magnitude [see to bring in the money…]:
September 27, 2010
I’ve spent no small amount of time raling about the invasion of the Pharmaceutical Industry into Academic Medicine, specifically at Emory University where I trained and worked for some time. The Chairman, Dr. Charles Nemeroff, was relieved of his Chair in 2008 because of repeated Conflict of Interest violations. Since then, he has moved on to become the Chairman at the Miller School of Medicine in Miami. You might wonder why Miami would recruit a tarnished person, or why Emory put up with his antics so long. That question has an answer. Dr. Nemeroff came to Emory in 1991. At that time, the Department at Emory had no National Institute of Mental Health Grants. In the NIH/NIMH database, the funding amounts for grants only goes back 10 years, so I’ve shown the total number of grants above for the whole period and added the total funding below for the last decade:

Dr. Nemeroff came in 1991, and stepped down under a cloud of allegations in the Fall of 2008. By that year, the Department was bringing in 18 Million Dollars yearly from NIMH Grants [up from zero when he came]. And that only includes NIMH Government Grants. While I have no access to the amounts, there was also plenty of Pharmaceutical Industry money coming Emory’s way as well during those years through Dr. Nemeroff’s efforts.
I ran across that old post today and was amazed as I was the day I compiled it. That’s a lot of money, and there was plenty of PHARMA money coming in too – study grants and unrestricted institutional grants. I had wondered why the University had tolerated Nemeroff’s antics, but wonder no more. He came in 1991, and brought in an army of researchers who brought in the money. While this is a dramatic version, this trend was manifest all over the country. On a lark, I thought I’d look into what has happened since he was asked to step down in the wake of Senator Grassley’s expose of his personal PHARMA Income in 2008.

The research program Dr. Nemeroff built is holding its own. Obviously, the thing we would all like to know about is the PHARMA income coming in. What was it then? What is it now? There is no way I know of to get at those figures, but I’m absolutely sure that now is remarkably less than then [as PHARMA has moved on to greener pastures].

Unless you’ve been in Academic Medicine, you would have no way of knowing how medical education actually works. There is very little Institutional Support from the Universities. Much of the teaching is done by volunteer clinicians [unpaid]. In most medical specialties, the departments support themselves by delivering services – hospitals, clinics, etc. In psychiatry, we just don’t generate money like the rest of medicine – don’t even come close. In the 1950s and particularly 1960s, there was heavy government funding to support the Community Mental Health services flowering at the time. So departments of psychiatry were heavily invested in and supported by public medicine. In the 1970s, those resources were waning fast, and with Reagan’s election in 1980, they virtually disappeared. Managed Care was slashing psychiatric services at the same time [also a resource  for psychiatry departments]. Those were my days in academic medicine, and we were operating hand to mouth [on our best days].

So the government money from the NIMH heavily favored biological research; PHARMA was paying handsomely for academic connections offering lucrative institutional and product testing grants; and Managed Care was only paying psychiatrists to do medication management. Is it any wonder what happened in psychiatry? It was Darwin 101 – Natural Selection and Survival of the Fittest. Universities chose chairmen who could build like Charlie Nemeroff, who hired faculty who could bring in the government and PHARMA research money, and here we are today. That doesn’t make it right, but it’s what happened.
Mickey @ 6:30 AM


Posted on Sunday 14 June 2015

    re·form  [ri-‘fôrm]
    1. make changes in something [typically a social, political, or economic institution or practice] in order to improve it.
In this case, my preferred definition is more literal: re·form = to form again
U scientists will have to choose: Research or consulting fees.
Star Tribune
By Maura Lerner
June 12, 2015

For the first time, University of Minnesota scientists will be barred from accepting consulting fees from companies that sponsor their research, under a new ethics plan endorsed Friday by the Board of Regents. President Eric Kaler says the new rule, which is designed to guard against conflicts of interest, is one of the strictest in the country among academic research centers.

The regents unanimously endorsed the 75-page plan, which recommends a series of changes to tighten safeguards for patients who volunteer in university research trials. The plan was commissioned in the wake of widespread criticism of research practices at the U’s psychiatry department and its handling of a 2004 drug study during which a 27-year-old patient, Dan Markingson, committed suicide. Dr. William Tremaine of the Mayo Clinic, who led the task force that drafted the plan, said that one of the goals is to ensure that vulnerable patients like Markingson, who had schizophrenia, “know what they’re getting into” and aren’t coerced into studies.

“That’s been a huge concern at the university over the last 11 years,” Tremaine said Thursday, as he briefed the regents on the proposals. The plan calls for beefing up scrutiny of research involving patients, and paying experts to serve on oversight panels.  It also takes a harder line on potential conflicts of interest. In the past, U scientists were permitted to do research for drug companies while serving as their paid consultants at the same time. Under the new plan, they’ll have to choose one or the other, Tremaine said. “That’s going to be threatening to some individuals,” he noted. “It’s your choice. If you want the payments, then don’t do the research.”

Dr. Charles Schulz, who stepped down as chairman in April after a series of scathing reports about his department, was one of the psychiatrists involved in the Markingson case. He said he thought the changes were “very appropriate.” Schulz acknowledged that he had received consulting fees in the past while conducting industry-sponsored research. At the time, he said, it was permitted as long as the payments were disclosed; but he said he understands the university’s move to change the rules. “That’s not an unreasonable plan for the university,” he said. “I think it’s going to be a very good plan.”

Schulz said he will retire at the end of the year.
We can only watch what’s happening at the University of Minnesota with something akin to awe. Carl Elliot and his associates have taken the phrase, "Sunlight is said to be the best of disinfectants," to new heights:
Supreme Court Justice Louis Brandeis’ article in the December 20, 1913 edition of Harper’s Weekly is often cited for his maxim, “Sunlight is said to be the best of disinfectants.” The article, entitled What Publicity Can Do, was one of a series of articles he compiled into a book he published; Other People’s Money and How the Bankers Use It. Brandeis asserted that transparency was a necessary reform to check the power of large banks. His theories served as the foundation for the establishment of the Federal Trade Commission…
Whether by design or instinct, Carl Elliot et al have followed the playbook of Louis Brandeis to the letter. Brandeis was a lawyer who called attention to broader social issues by taking on exemplar individual cases and keeping them in the sunlight, ultimately leading to his quarter century tenure as a Supreme Court Justice. In much the same way, the tragedy of Dan Markingson’s death has been the specific focus for the bioethicists at the University of Minnesota, but it’s leading to palpable changes which will be widely influential in the lives of many others to come.

Mickey @ 1:10 PM

not backward…

Posted on Friday 12 June 2015

by Fiona Godlee
British Medical Journal. 2015 350:h3176
[Published 11 June 2015]

The New England Journal of Medicine has refuelled the smouldering debate on conflicts of interest. In a surprising series of articles and an editorial by its editor in chief, Jeffrey Drazen, the journal seems to signal a retreat from current efforts to tackle financial conflicts of interests in medicine:
There has been no shortage of critical response, including in The BMJ. In an editorial I and colleagues conclude that it’s a mistake to suggest that rigorous standards should be revisited
And an accompanying article by three former editors of the New England Journal of Medicine, Robert Steinbrook, Jerome P Kassirer, and Marcia Angell, calls its series of articles “a seriously flawed and inflammatory attack” that tries to rationalise conflicts of interest in the medical profession
They fear a further weakening of conflict of interest policies at the New England Journal of Medicine and hope that its stance will serve as a wake-up call. Other contributions to the debate come from bloggers surprised and concerned at the journal’s new stance:
Indeed it’s hard to find support for the New England Journal of Medicine’s move. Richard Horton, editor of the Lancet, comes closest:
The truth, he says, lies somewhere between these extremes.

So where is this common ground? No one doubts the need for a vibrant drug and devices sector that serves patients and populations. Nor does anyone seriously question that, to deliver this, the industry must interact with researchers and understand the needs of patients and clinicians. And there is little dispute that non-financial conflicts of interest — such as academic passion and personal belief — are just as important, if harder to track.

Has the debate been useful? Horton thinks so, and I agree. Two clarifications in particular. Firstly, this is not a moral but a practical issue. As Steinbrook and colleagues say, it should not be insulting to suggest that a person’s judgment can be affected by financial relationships. “The concern is not whether physicians and researchers who receive money have been bought by the drug companies … The essential issue is that it is impossible for editors and readers to know one way or another.”

Secondly, the same person or people shouldn’t be asked to produce the evidence and appraise it. As our editorial says, “These are different professional responsibilities, and they clash.” The BMJ’s new policy on conflicts of interest among authors of educational articles seeks to make clear this distinction
Ironically, we took as our model the New England Journal of Medicine’s former policy, which set similar rules. These are hard to implement, but we are determined to push on, evaluating as we go. Our aim is not only to ensure that our educational content can be trusted but to encourage culture change in medicine in the interests of patients and the public. We seek experts in all fields of medicine who do not have relevant financial relations with the industry. If you are such a person and would like to contribute, please email us:
so we can add you to our growing database.
No, this isn’t just posted to crow about this blog making the BMJ editorial page, though I admit to feeling proud. It’s here because of that line up there in red:
“The concern is not whether physicians and researchers who receive money have been bought by the drug companies … The essential issue is that it is impossible for editors and readers to know one way or another.”
Unlike Dr. Godlee, I do have some concern that "physicians and researchers who receive money have been bought by the drug companies," but she’s right, the main concern "is that it is impossible for editors and readers to know one way or another." I would hold that it is virtually impossible for a conflict of interest not to have an impact on one’s opinion. I just don’t want to spend my time reading something spending my time thinking about the author’s bias, and never knowing the answer. I’d rather read the thoughts of a "lesser expert."

If you want to be a scholar, an academic expert, don’t sign on to a company. If you want to work for industry, don’t pretend you’re a scholar. And by the way, if you’re not an open conduit into the scientific literature, do you think they’ll hire you? Here’s an example from the paradigm of COI:

The graph is the number of companies he was a paid to advise by year. Note what happened when Dr. Grassley investigated him – and the ones  left were in the minor leagues. If it were his expertise that mattered, it would’ve been a different story. Certainly there have been genuine experts who worked for/with industry as documented in Rosenbaum’s articles, but they were exceptions to the rule [and we all know that]. The usual hire is for a ticket into the literature.

And speaking of rationalizations, see Psycritic’s Conflicts of Interest for a classic. As Dr. Godlee’s editorial title says, "Conflict of interest: forward not backward."
Mickey @ 11:16 PM