1 Boring Old Man

Funds Join Campaign to Pressure Pharma to Disclose Trial Data

Pharmalot

By Ed Silverman

07/22/2015

The investors, which collectively manage about $3.8 trillion, plan to meet with drug makers in which they invest to ensure that trials are registered and results are reported, according to Sile Lane, campaign director at Sense About Science, a non-profit that launched the AllTrials campaign. In an unprecedented move, a group of 85 asset managers and pension funds is teaming with a U.K. non-profit campaign to pressure drug makers to disclose clinical trial data. The effort is likely to escalate a closely watched battle that has increasingly placed the pharmaceutical industry on the defensive as researchers and regulators call for increased disclosure in the U.K. to agitate for greater trial data disclosure.

Drug makers will be asked to retrospectively register past and ongoing clinical trials, and register all future trials before they begin; publish methods and full results of all trials, include information on adverse events; post objective summary results within one year of completing a trial, and support efforts to provide independent researchers access to anonymized individual patient data, according to a statement. “We believe this is going to be game changing,” Lane tells us. To facilitate the process, the AllTrials campaign is conducting an audit of disclosure policies for the 50 largest drug makers and will score each one. The results are expected to be published in September. “This will become a tool readily available to investors,” she says.

The move comes amid growing clamor from academics and consumer groups to press drug and device makers to release trial data. At issue is the ability for researchers to independently verify study results and, consequently, improve patient treatments that can lead to better health and lower costs. Concerns have been heightened following various safety scandals that revealed trial data for some products was never fully published or disclosed. In recent months, regulators in the U.S. and Europe have responded by releasing new rules designed to widen access. And several drug makers, in varying degrees, have taken steps to release trial data.

For instance, GlaxoSmithKline created a website where data requests are made to 10 different drug makers, Johnson & Johnson is working with Yale University to provide access to data, and Bristol-Myers Squibb will grant access to academics as part of a collaboration with Duke University. AstraZeneca formed a panel to review requests for data, although questions were raised about its independence. But critics say such efforts are few and far between. Helena Vines Fiestas, who heads sustainability research at BNP Paribas, says there is increasing concern that a lack of transparency about medicines – past and present – is having a negative impact on stock valuations. BNP got involved as an outgrowth of a broader effort to rate and benchmark companies in different industry sectors.

For instance, she says fines paid by 21 drug makers for marketing malfeasance between 2007 and mid-2015 was $40 billion, and 43% was directly related to minimizing side effects that were identified during clinical trials but not properly reported. Her team also queried analysts and discovered that an average of about 30% of drug company stock valuations directly relate to results of Phase III clinical trials.

“The lack of complete and unbiased information can mislead decisions made not only regulators and doctors, but also investors,” Fiestas tells us. “We think if the companies become more transparent and take the issue around auditing and reports more seriously that the decisions made by analysts can be more closely aligned with reality”…

Psychiatry’s Identity Crisis

New York Times

by Richard A. Friedman

Contributing Op-Ed Writer

July 17, 2015

AMERICAN psychiatry is facing a quandary: Despite a vast investment in basic neuroscience research and its rich intellectual promise, we have little to show for it on the treatment front. With few exceptions, every major class of current psychotropic drugs — antidepressants, antipsychotics, anti-anxiety medications — basically targets the same receptors and neurotransmitters in the brain as did their precursors, which were developed in the 1950s and 1960s. Sure, the newer drugs are generally safer and more tolerable than the older ones, but they are no more effective…

At the same time, judging from research funding priorities, it seems that leaders in my field are turning their backs on psychotherapy and psychotherapy research. In 2015, 10 percent of the overall National Institute of Mental Health research funding has been allocated to clinical trials research, of which slightly more than half — a mere 5.4 percent of the whole research allotment — goes to psychotherapy clinical trials research.

As a psychiatrist and psychopharmacologist who loves neuroscience, I find this trend very disturbing. First, psychotherapy has been shown in scores of well-controlled clinical trials to be as effective as psychotropic medication for very common psychiatric illnesses like major depression and anxiety disorders; second, a majority of Americans clearly prefer psychotherapy to taking medication…

Finally, many of our patients have histories of trauma, sexual abuse, the stress of poverty or deprivation. There is obviously no quick biological fix for these complex problems. Still, there has been a steady decline in the number of Americans receiving psychotherapy along with a concomitant increase in the use of psychotropic medication in those who are treated in the outpatient setting. These trends are most likely driven by many factors, including cost and the limited availability that most Americans have to mental health practitioners. It is clearly cheaper and faster to give a pill than deliver psychotherapy…

More fundamentally, the fact that all feelings, thoughts and behavior require brain activity to happen does not mean that the only or best way to change — or understand — them is with medicine. We know, for instance, that not all psychiatric disorders can be adequately treated with biological therapy. Personality disorders, like borderline and narcissistic personality disorders, which are common and can cause impairment and suffering comparable to that of severe depression, are generally poorly responsive to psychotropic drugs, but are very treatable with various types of psychotherapy…

• guilding the lily…
• in a guilded cage… 
• the guilded age…
• the rise and ??? of the guild…

Psychiatry Now Admits It’s Been Wrong in Big Ways – But Can It Change?

Truthout

by Bruce Levine

March 5, 2014

Bruce Levine’s Question: Is it really possible for psychiatry to reform in any meaningful way given their complete embrace of the "medical model of mental illness," their idea that emotional and behavioral problems are caused by a bio-chemical defect of some type? Can they really reform when their profession as a financial enterprise rests on drug prescribing, electroshock and other bio-chemical-electrical treatments? Can psychiatry do anything but pay lip service to a more holistic/integrative view that includes psychological, spiritual, social, cultural and political realities?

Robert Whitaker’s Answer: I think we have to appreciate this fact: any medical specialty has guild interests, meaning that it needs to protect the market value of its treatments. If it is going to abandon one form of treatment, it needs to be able to replace it with another. It can’t change if there is no replacement in the offing. When the APA published DSM-III, it basically ceded talk therapy to psychologists, counselors, social workers and so forth…

… So I don’t believe it will be possible for psychiatry to change unless it identifies a new function that would be marketable, so to speak. Psychiatry needs to identify a change that would be consistent with its interests as a guild. The one faint possibility I see – and this may seem counterintuitive – is for psychiatry to become the profession that provides a critical view of psychiatric drugs. Family doctors do most of the prescribing of psychiatric drugs today, without any real sense of their risks and benefits, and so psychiatrists could stake out a role as being the experts who know how to use the drugs in a very selective, cautious manner, and the experts who know how to incorporate such drug treatment into a holistic, integrated form of care. If the public sees the drugs as quite problematic, as medications that can serve a purpose – but only if prescribed in a very nuanced way – then it will want to turn to physicians who understand well the problems with the drugs and their limitations. That is what I think must happen for psychiatry to change. Psychiatry must see a financial benefit from a proposed change, one consistent with guild interests.

But I’ll stop my rant. This blog isn’t about that old story. This blog is about honesty in science. But I guess it has been so long since someone acknowledged that psychiatrists are physicians who care for the sick, bringing to bear whatever might help – whether biologic, psychologic, sociologic, humanistic, cybernetic, etc. And that for many of our patients, psychotherapy of the kind I learned, practiced, and still practice is exactly what the doctor ordered. As for Whitaker’s thoughts about searching for a marketable skill or some new function. I guess I already have one, so I don’t need to ponder a Collaborative Care environment where I’m asked to be an expert consultant medicating patients I’ve never seen [which to me smells like malpractice].

• Long-term effects of antipsychotics
  Joanna Moncrieff
  BJPsych Advances March 2015, 78-79. DOI: 10.1192/apt.bp.114.012591
• Early schizophrenia: skilful management of medication
  John Cookson
  BJPsych Advances March 2015, 80-84. DOI: 10.1192/apt.bp.114.013359
• Patients need reliable facts and figures about antipsychotics
  Stephen M. Lawrie
  BJPsych Advances March 2015, 85-87. DOI: 10.1192/apt.bp.114.013375

Antipsychotics can effectively reduce acute psychotic symptoms in many people, but evidence on the benefits of long-term treatment is more equivocal, and recent evidence underlines their potentially negative effect on brain volume, alongside other serious physical complications. NICE [2014] recommends more research into long-term outcomes of antipsychotic discontinuation. In the meantime, recent evidence suggests that a trial of supported antipsychotic discontinuation should be considered as one option in the routine treatment of people with psychotic conditions. This strategy may help some people to improve their functioning and quality of life, and reduce the risks to their physical health.

Only about 20% of those in the dose reduction/discontinuation group actually managed to discontinue their antipsychotic medication at all. There were no actual differences between the dose reduction/discontinuation and maintenance treatment groups in social function or quality of life, and the mean dose of antipsychotic over the previous 2 years was only about 1.5 mg different in haloperidol equivalents [~2 mg v. ~3.5 mg daily]. In the final analysis, only 8 individuals in the dose reduction/discontinuation group and 3 in the maintenance treatment group had sustained antipsychotic discontinuation during the 7-year follow-up.

What it actually shows is that antipsychotic discontinuation is rarely feasible and that slow tapering of the dose down to an average of about 2 mg haloperidol equivalents is associated with some measures of functional improvement. Indeed, the results are entirely in keeping with treatment guidelines which suggest that antipsychotic medication should be maintained for 2 years and then phased withdrawal attempted. What the trial suggests we really need is not new strategies for managing antipsychotic treatment after a first episode, but a way of identifying the small number of patients who can manage without antipsychotics.

The enthusiastic embrace by Moncrieff of Wunderink et al’s 7-year follow-up of a 2-year randomised controlled trial of treatment for first-episode psychosis is understandable. But any eagerness to dismiss the usefulness of long-term treatment with antipsychotics is premature. The results are counter-intuitive and seem to have puzzled the authors themselves and to invite speculative explanations.

The main finding of the Wunderink et al study is that after 7 years, 30 people from the original 128 with a first episode of non-affective psychosis were identified as being in recovery, with symptomatic and functional remission; of these, 25 were on no medication at that time. This group represented about half of the patients eligible for the study. The findings tell us that skilful management of medication is important in helping patients to achieve more complete remission of functional impairments after a diagnosis of schizophrenia-like illness.

It remains advisable for patients with a first episode of schizophrenia or other non-affective psychosis to continue on medication for at least 1 year after remission of the episode and/or discharge from hospital. A proportion of patients who remain well 1 year later may not require further antipsychotic medication, but there is no reliable way of identifying these, other than by a gradual discontinuation of medication. Those with a longer initial DUI or with comorbid substance misuse are less likely to remain well for long without medication. For those requiring medication to remain well, adherence is important; the medication is not effective unless it is taken, and side-effects must be recognised. The management of dosage, choice of antipsychotic and achievement of adherence require close clinician–patient relationships with skilful clinical management, as does advice to the families and carers. 

Wunderink is one of those studies that gets discussed and analyzed over and over – something of a Rorschach ink·blot for the pre-existing opinion of the reader. Those who  are opposed to maintenance antipsychotic treatment point to the greater functional recovery in the group of patients in the reduction/discontinuation group at seven years. Those who support maintenance antipsychotic treatment note that very few patients could actually get off of antipsychotics entirely in either group of this study. The patients in the reduction/discontinuation group were on a lower mean dose in the years following the original 18 month study, suggesting that the improved functional recovery might be related to the lower dosing regimens.

I must say that my own limited and anecdotal experience mirrors these results somewhat. I left training with the attitude that lower·dose or better-yet, medication·free, was the laudable goal, but wasn’t altogether able to bring it off. Getting people medication·free was invariable followed by relapse, and I settled for the lower·dose route unless directed otherwise by the patient’s choice. Those selecting medication·free either restarted medication or relapsed and ended up on a higher dose. In theory, perhaps, relapse is not necessarily a bad thing, but in practice, it was a major disruption in the interpersonal and vocational lives of the patients I followed. A couple sustained medication·free·ness, but it was way late in the game.

Of course, only one study indicating advantages of a DR strategy in patients with remitted FEP is not enough evidence in such an important matter. However, these results merit replication by other research groups.

Revisiting the Commercial–Academic Interface
Reconnecting the Dots — Reinterpreting Industry–Physician Relations
Understanding Bias — The Case for Careful Study
Beyond Moral Outrage — Weighing the Trade-Offs of COI Regulation

a contrarian frame of mind…
wtf?… 
wtf? for real… 
a narrative… 
not so proud… 
unserious arguments seriously… 
the real editors speak out… 
got any thoughts?… 
not backward… 

Competing interests are a complex problem

Part I of a series on conflicts of interest in medicine

Canadian Medical Association Journal

by Roger Collier

July 16, 2015

… In an ideal world, there would perhaps be no need for a conversation about conflicts of interest in medical research. Academic researchers with good ideas for new medications would have all the funding and resources they need to manufacture compounds and launch large-scale clinical trials without support from industry. That, however, is not reality. Today, like it or not, the expensive and risky process of getting new medications into the hands of patients requires resources unavailable in academic laboratories. "We are in the business of making patients better," said Drazen, a pulmonologist. "When you develop something and want to take it that last step, from a general idea to making a difference for patients, you really need a way to work with commercial entities"…

"The problem is that people are taking the marketing arm, where doctors are selling a drug, and they conflate it with the discovery arm, where we want to encourage interaction," said Drazen. "We need to figure out a way for researchers to work with commercial entities that won’t paint them as having sold their soul to the devil."

If negative attitudes about all financial ties between doctors and industry don’t change, they will continue to undermine innovation in medicine, according to Dr. Thomas Stossel, author of the book Pharmaphobia. Over the course of his lengthy career, the practice of medicine has improved tremendously, said Stossel. He attributes that improvement to better tools, most of which came from the medical-products industry. "We get that stuff at great difficulty and at great expense," said Stossel, director of translational medicine at Brigham and Women’s Hospital in Boston, Massachusetts. "With respect to innovation, intelligent, educated people — even doctors — have no idea. They think this stuff comes from Santa Claus"…

Next: Part II: The costs of vilifying pharma

To Support Physician Decision-Making, Re-Evaluate Industry Funding Of Science

Health Affairs Blog

by Christopher Robertson

July 16, 2015

In 1984, the New England Journal of Medicine [NEJM] began requiring authors of research papers to disclose financial relationships with the pharmaceutical or device industry. The policy was controversial then, and even a decade later still faced criticism, with noted scholars charging that it “thwarts the principle that a work should be judged solely on its merits.”

Though every respectable scientific journal has now adopted such a policy, this critical view has received new attention in a three-part series on conflicts of interest appearing in NEJM, again asking whether disclosures “foster an ad hominem approach to evaluating science.” Three former NEJM editors fired back in the pages of The BMJ, calling this a “seriously flawed and inflammatory attack” on a longstanding consensus about conflicts of interest. Who is right?

It is tempting to answer with heated rhetoric about “industry greed” and the “taint” of industry money, or with a romantic account of the “life-saving innovations” funded by industry. But both arguments miss the point. The question should be simply whether disclosures will support physician decision-making and ultimately enhance patient health outcomes. And more fundamentally, whether there are better models for funding science…

"With few exceptions, every major class of current psychotropic drugs — antidepressants, antipsychotics, anti-anxiety medications — basically targets the same receptors and neurotransmitters in the brain as did their precursors, which were developed in the 1950s and 1960s."

So I, for one think that the New England Journal’s argument is not applicable to psychiatry, and probably equally flawed in other specialties. If there are no "untainted" academics to write editorials and review articles, then I’d just as soon we do without editorials and review articles. In fact, the point being made in the CMAJ article above that only Pharmaceutical Companies have the resources to do drug research is an even stronger argument to keep academics that write editorials and reviews free of industry connections. Who else is going to counter the barrage of hype that comes when each new drug becomes available?

• C.I.A., on Path to Torture, Chose Haste Over Analysis 15 December 2014
• American Psychological Association’s Role in Bush-Era Interrogation Program April 2015
• Outside Psychologists Shielded U.S. Torture Program, Report Finds 10 July, 2015
• Psychologists Who Greenlighted Torture 10 July, 2015
• US torture doctors could face charges after report alleges post-9/11 ‘collusion’ 11 July, 2015
• Three senior officials lose their jobs at APA after US torture scandal 12 July, 2015
• ‘A national hero': psychologist who warned of torture collusion gets her due 13 July, 2015
• Three senior officials lose their jobs at APA after US torture scandal 14 July, 2015
• Torture, American-Style: The Role of Money in Interrogations 14 July, 2015

When Psychiatrist Major Paul Burney arrived at Guantanamo Bay in June 2002, he was unaware that he would be assigned to BSCT [Behavioral Science Consultation Team] to support interrogations.

[1] Three of us; [the enlisted psychiatric technician], and I, were hijacked and immediately in processed into Joint Task Force 170, the military intelligence command on the island. It turns out we were assigned to the interrogation element because Joint Task Force 170 had authorizations for a psychiatrist, a psychologist, and a psychiatric technician on its duty roster but nobody had been deployed to fill these positions. Nobody really knew what we were supposed to do for the unit, but at least the duty roster had its positions filled.

They knew nothing of interrogation, so the psychologist contacted a psychologist he had met, LTC Banks, who was [unknown to the contacting psychologist] working with SERE. Banks set out to arrange training. BSCT thought they were going there just to learn about interrogation, but their CO wanted them to bring back SERE techniques to try.

[2] At the time, there was a view by some at GTMO that interrogation operations had not yielded the anticipated intelligence, MAJ Burney testified to the Army IG regarding interrogations: "This is my opinion, even though they were giving information and some of it was useful, while we were there a large part of the time we were focused on trying to establish a link between al Qaeda and Iraq and we were not being successful in establishing a link between al Qaeda and Iraq. The more frustrated people got in not being able to establish this link, there was more and more pressure to resort to measures that might produce more immediate results."

The point is simply that besides being an indelible blot on the moral integrity of our country and failing to yield anything of any worth to us, the Torture Program was actually used as a tool to take advantage of our wounded and frightened state to trump up a reason to invade a sovereign country that had nothing to do with 911 by trying to link al Qaeda and Iraq, probably partly motivated to gain access to Iraq’s oil reserves and partly as a showpiece for their Project for the New American Century – AKA American Dominion on the world stage. So why did the APA Ethics Director, Stephen Behnke, and his cohort in the APA leadership do it? Was he part of the Bush Administration megalomania. No, it was something much simpler…

APA’s motive to please DoD

The very substantial benefits APA obtained from DoD help explain APA’s motive to please DoD. and show that APA likely had an organizational conflict of interest, which it needed to take steps to guard against. DoD is one of the largest employers of psychologists and provides many millions of dollars in grants or contracts for psychologists around the country. The history of DoD providing critical assistance to the advancement and growth of psychology as a profession is well documented, and includes DoD’s creation of a prescription-privileges "demonstration project" in which psychologists were certified to prescribe psychiatric drugs within DoD after going through a two-year training course… And by the time of the PENS Task Force, contemporaneous internal discussions show that improving APA’s already strong relationship with DoD was a clear priority for officials working on the PENS Task Force.

In addition, at the time of the task force’s creation, DoD was in the midst of developing policy about how psychologists and psychiatrists could participate in interrogations and other intelligence-collection activities. APA wanted to positively influence DoD regarding this policy so that psychologists would be included to the maximum degree possible, and psychologists would not lose the lead role to psychiatrists. APA used the pro-DoD task force composition and report to show its strong support to DoD, with the hope or expectation that APA would be rewarded with a very prominent role for psychologists in this new policy. And in fact, the policy did provide a very prominent role for psychologists, a fact celebrated by the APA officials who had worked most closely on the task force…

Behnke failed to proceed with and actively resisted proceeding with these complaints. The evidence shows that Behnke knew that the adjudications process was not equipped to address ethical complaints regarding psychologists’ participation in interrogations — and that it would not lead to any sort of meaningful or thorough investigation.

The end result of the limited nature of the ethics investigations and the Ethics Office’s purposeful unwillingness to thoroughly investigate allegations of unethical conduct by psychologists who participated in interrogations was that the Ethics Office prioritized the protection of psychologists — even those who might have engaged in unethical behavior — above the protection of the public.

• American Psychiatric Association policy on interrogation 2006
• American Medical Association policy on interrogation 2006

After 911, the country was united in a surge of patriotic zeal that the Bush Administration used to take us into a war with Iraq that we would have declined in other circumstances. The prisoner abuse at Abu Ghraib prison and torture at Guantanamo Bay were among the many disillusioning revelations that came out of that war. We learned that two DoD contract psychologists, Jim Mitchell and Bruce Jessen, had a central role in the development and implementation of the enhanced interrogation techniques [AKA Torture]. Less widely known, the APA [American Psychological Association] also had a part in this story – specifically addressing the ethical obligations of the psychologists involved in the interrogation process.

Press Release and Recommended Actions: Independent Review Cites Collusion Among APA Individuals and Defense Department Officials in Policy on Interrogation Techniques

American Psychological Association

June 10, 2015

… The Hoffman report contains deeply disturbing findings that reveal previously unknown and troubling instances of collusion,” said Dr. Susan McDaniel, a member of the Independent Review’s Special Committee. “The process by which the Presidential Task Force on Psychological Ethics and National Security [PENS] was created, the composition of the membership, the content of the PENS report and the subsequent activities related to the report were influenced by collusion between a small group of APA representatives and government officials.

The Hoffman report states that the intent of the individuals who participated in the collusion was to “curry favor” with the Defense Department, and that may have enabled the government’s use of abusive interrogation techniques. As a result, the 2005 PENS report became a document based at least as much on the desires of the DoD as on the needs of the psychology profession and the APA’s commitment to human rights…

The Hoffman Report

Sidley Austin law firm

by Douglas Hoffman

Commisioned by the American Psychological Association

June 2015

«from the Hoffman Report, page 14»

APA’s motive to please DoD

The very substantial benefits APA obtained from DoD help explain APA’s motive to please DoD. and show that APA likely had an organizational conflict of interest, which it needed to take steps to guard against. DoD is one of the largest employers of psychologists and provides many millions of dollars in grants or contracts for psychologists around the country. The history of DoD providing critical assistance to the advancement and growth of psychology as a profession is well documented, and includes DoD’s creation of a prescription-privileges "demonstration project" in which psychologists were certified to prescribe psychiatric drugs within DoD after going through a two-year training course. While APA took one significant step in 1991 that disappointed many military psychologists — refusing to allow DoD ads in APA’s publications because of DoD’s discriminatory position regarding gays and lesbians in the military — APA had lifted its advertising ban in 2004. And by the time of the PENS Task Force, contemporaneous internal discussions show that improving APA’s already strong relationship with DoD was a clear priority for officials working on the PENS Task Force.

In addition, at the time of the task force’s creation, DoD was in the midst of developing policy about how psychologists and psychiatrists could participate in interrogations and other intelligence-collection activities. APA wanted to positively influence DoD regarding this policy so that psychologists would be included to the maximum degree possible, and psychologists would not lose the lead role to psychiatrists. APA used the pro-DoD task force composition and report to show its strong support to DoD, with the hope or expectation that APA would be rewarded with a very prominent role for psychologists in this new policy. And in fact, the policy did provide a very prominent role for psychologists, a fact celebrated by the APA officials who had worked most closely on the task force…

«from the Hoffman Report, page 9»

lV. SUMMARY OF THE INVESTIGATION’S CONCLUSIONS

Our principal findings relate to the 2005 task force, which was formally empaneled by the APA President and was called the Presidential Task Force on Ethics and National Security, or "PENS." The task force finalized a report on June 26, 2005 containing 12 ethical guidelines that were adopted as official APA ethics policy by the APA Board on an emergency basis less than one week later.

Our investigation determined that key APA officials, principally the APA Ethics Director joined and supported at times by other APA officials, colluded with important DoD officials to haw APA issue loose, high-level ethical guidelines that did not constrain DoD in any greater fashion than existing DoD interrogation guidelines. We concluded that APA’s principal motive in doing so was to align APA and curry favor with DoD. There were two other important motives: to create a good public-relations response, and to keep the growth of psychology unrestrained in this area.

We also found that in the three years following the adoption of the 2005 PENS Task Force report as APA policy, APA officials engaged in a pattern of secret collaboration with DoD officials to defeat efforts by the APA Council of Representatives to introduce and pass resolutions that would haw definitively prohibited psychologists from participating in interrogations at Guantanamo Bay and other U.S. detention centers abroad. The principal APA official involved in these efforts was once again the APA Ethics Director, who effectively formed an undisclosed joint venture with a small number of DoD officials to ensure that APA’s statements and actions fell squarely in line with DoD’s goals and preferences. In numerous confidential email exchanges and conversations, the APA Ethics Director regularly sought and received pre-clearance from an influential, senior psychology leader in the U.S. Army Special Operations Command before determining what APA’s position should be. what its public statements should say. and what strategy to pursue on this issue…

Another proud moment for the ethics business
Psychologists Shielded U.S. Torture Program, Report Finds

Another lightning strike! Awaiting Internet repair…

Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Disruptive Behaviors in Children With Subaverage Intelligence

by Michael G. Aman, Ph.D., Goedele De Smedt, M.D., Albert Derivan, M.D., Ben Lyons, Ph.D., Robert L. Findling, M.D., and the Risperidone Disruptive Behavior Study Group

American Journal of Psychiatry 2002 159:1337-1346.

[ClinicalTrials.gov Identifier: NCT00266552]

Objective: The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence.

Method: In this 6-week, multicenter, double-blind, parallel-group study of 118 children [aged 5-12 years] with severely disruptive behaviors and subaverage in- telligence [IQ between 36 and 84, inclusive], the subjects received 0.02-0.06 mg/kg per day of risperidone oral solution or placebo. The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscalc of the Nisonger Child Behavior Rating Form.

Results: The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint [change in score of -15.2 and -6.2, respectively]. Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoinl. as well as on the Aberrant Behavior Checklist subscales for irritability, lethargy-social withdrawal, and hyperactivity; the Behavior Problems Inventory aggressive -destructive behavior subscale; a visual analogue scale of the most troublesome symptom; and the Clinical Global Impression change score. The most common adverse effects reported during risperidone treatment were headache and somnolence. The extrapyramidal symptom profile of risperidone was comparable to that of placebo. Mean weight increases of 2.2 kg. and 0.9 kg occurred in the risperidone and placebo groups, respectively.

Conclusions: Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ.

Treatment of Young People With Antipsychotic Medications in the United States

by Mark Olfson, MD, MPH; Marissa King, PhD; Michael Schoenbaum, PhD

JAMA Psychiatry. online July 01, 2015. doi:10.1001/jamapsychiatry.2015.0500.

[full text on-line]

Importance Despite concerns about rising treatment of young people with antipsychotic medications, little is known about trends and patterns of their use in the United States.

Objective To describe antipsychotic prescription patterns among young people in the United States, focusing on age and sex.

Design, Setting, and Participants A retrospective descriptive analysis of antipsychotic prescriptions among patients aged 1 to 24 years was performed with data from calendar years 2006 [n = 765,829], 2008 [n = 858,216], and 2010 [n = 851,874], including a subset from calendar year 2009 with service claims data [n = 53,896]. Data were retrieved from the IMS LifeLink LRx Longitudinal Prescription database, which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population.

Main Outcomes and Measures The percentage of young people filling 1 or more antipsychotic prescriptions during the study year by sex and age group [younger children, 1-6 years; older children, 7-12 years; adolescents, 13-18 years; and young adults, 19-24 years] was calculated. Among young people with antipsychotic use, percentages with specific clinical psychiatric diagnoses and 1 or more antipsychotic prescriptions from a psychiatrist and from a child and adolescent psychiatrist were also determined.

Results The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults. In 2010, males were more likely than females to use antipsychotics, especially during childhood and adolescence: 0.16% vs 0.06% for younger children, 1.20% vs 0.44% for older children, 1.42% vs 0.95% for adolescents, and 0.88% vs 0.81% for young adults. Among young people treated with antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children [57.9%] than among other age groups [range, 70.4%-77.9%]. Approximately 29.3% of younger children treated with antipsychotics in 2010 received 1 or more antipsychotic prescriptions from a child and adolescent psychiatrist. Among young people with claims for mental disorders in 2009 who were treated with antipsychotics, the most common diagnoses were attention-deficit/hyperactivity disorder in younger children [52.5%], older children [60.1%], and adolescents [34.9%] and depression in young adults [34.5%].

Conclusions and Relevance Antipsychotic use increased from 2006 to 2010 for adolescents and young adults but not for children aged 12 years or younger. Peak antipsychotic use in adolescence, especially among boys, and clinical diagnosis patterns are consistent with management of developmentally limited impulsive and aggressive behaviors rather than psychotic symptoms.

Peak antipsychotic use in adolescence, especially among boys, and clinical diagnosis patterns are consistent with management of developmentally limited impulsive and aggressive behaviors rather than psychotic symptoms.

Clinical policy makers have opportunities to promote improved quality and safety of antipsychotic medication use in young people through expanded use of quality measures, physician education, telephone- and Internet-based child and adolescent psychiatry consultation models, and improved access to alternative, evidence-based psychosocial treatments.

The place of antipsychotics in the treatment of Psychosis remains clouded in controversy in spite of more than a half century of study, experience, and debate. Neither Kraepelin’s Dementia Praecox, a progressive deteriorating illness leading to an early death, nor Bleuler’s Schizophrenia, a defined syndrome with multiple types, survives as the dominant model for predicting the course of illness. We now tend to see episodes of psychosis punctuating a variable level of functional impairment over time. While traditional guidelines call for maintenance medication based on relapse prevention, long term studies document that many patients regularly discontinue the treatment. And others feel strongly that maintenance medication itself interferes with recovery. Both of these opposing recommendations are backed by studies, anecdotal case reports, passionate ideologies, and interpretations of the bias of the opposing view. Since these medication have now been around now for a lifespan we’re seeing large population surveys that bear on this controversy. This one’s from Scandanavia, a traditional resource for this big population studies:

Antipsychotic treatment and mortality in schizophrenia.

by Torniainen M, Mittendorfer-Rutz E, Tanskanen A, Björkenstam C, Suvisaari J, Alexanderson K, and Tiihonen J.

Schizophrenia Bulletin. 2015 41[3]:656-663.

BACKGROUND: It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view.

METHODS: We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 [N = 21 492], aged 17-65 years, and persons with first-episode schizophrenia during the follow-up 2006-2010 [N = 1230]. Patient information was prospectively collected through nationwide registers. Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010.

RESULTS: Compared with age- and gender-matched controls from the general population [N = 214920], the highest overall mortality was observed among patients with no antipsychotic exposure [hazard ratio [HR] = 6.3, 95% CI: 5.5-7.3], ie, 0.0 defined daily dose [DDD]/day, followed by high exposure [>1.5 DDD/day] group [HR = 5.7, 5.2-6.2], low exposure [<0.5 DDD/day] group [HR = 4.1, 3.6-4.6], and moderate exposure [0.5-1.5 DDD/day] group [HR = 4.0, 3.7-4.4]. High exposure [HR = 8.5, 7.3-9.8] and no exposure [HR = 7.6, 5.8-9.9] were associated with higher cardiovascular mortality than either low exposure [HR = 4.7, 3.7-6.0] or moderate exposure [HR = 5.6, 4.8-6.6]. The highest excess overall mortality was observed among first-episode patients with no antipsychotic use [HR = 9.9, 5.9-16.6].

CONCLUSIONS: Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.

While the implications of this study may seem to conflict with other oft·quoted papers [eg Wunderink, Harrow, etc] the outcome parameters are different – functional improvement there vs overall mortality here. Further, all of these reports can’t possibly factor in the most confounding variable of all – the unique clinical field that the patient, the clinician, and the family face at any given moment in time. So reading the blogs, the individual case reports, and the various commentaries on this topic can be confusing as they often discuss these decisons as if they fall into the domain of morality – using maintenance medication is good as opposed to using maintenance medication is bad.

South Carolina House votes to remove Confederate flag from statehouse grounds

Washington Post

By Elahe Izadi and Abby Phillip

July 9, 2015

South Carolina Gov. Nikki Haley is set to sign a bill that will bring down the Confederate flag on the statehouse grounds, less than a day after lawmakers in the state House of Representatives voted to remove it. Haley, a Republican, called for the flag’s removal last month in the wake of the shooting massacre inside a Charleston church. The bill cleared its final legislative hurdle early Thursday morning when the House voted 94 to 20 in favor of the proposal.

After more than 13 hours of debate — which became increasingly contentious as the night wore on — House Republicans and Democrats agreed not to amend the legislation with a proposal that threatened to make final passage more difficult. Just before 1 a.m., the lawmakers voted 93 to 27 to move it forward in a critical second-reading vote. Minutes later, the bill easily cleared the two-thirds threshold needed for it to officially pass the chamber, a hurdle the state Senate cleared earlier this week.

If you didn’t grow up in the South in the 1940s and 1950s, you couldn’t possible imagine how big this is. That license plate on the right was on the front of many cars [in some places "most cars"] and "The South shall rise again!" was a stock phrase. Even those of us who were dedicated to racial equality and were marching in the streets saw that flag and those slogans, as having some misty-eyed meaning. That was wrong. And many of us figured that out along the way. But for the Legislature of the State of South Carolina to actually do something about it is truly a something I thought I’d never see. There will come a time when this something will be the history that South Carolinians are proud of…