lessons learned?…

Posted on Sunday 29 July 2012

I got diverted by the Olympics and cut short the last post. Such things happen. There was something else I wanted to say, but couldn’t think how to say it, so I threw in the towel for a bit. I liked the article, Psychiatry, The Pharmaceutical Industry, and The Road to Better Therapeutics, because it’s an honest appraisal of the state of the psychopharmacology research.
Psychopharmacology is in crisis. The data are in, and it is clear that a massive experiment has failed: despite decades of research and billions of dollars invested, not a single mechanistically novel drug has reached the psychiatric market in more than 30 years. Indeed, despite enormous effort, the field has not been able to escape the “me too/me [questionably] better” straightjacket.
Scientific advancement is never guaranteed. One can accelerated implementation [the Manhattan Project], but without the nidus of discovery and innovation [Einstein, Fermi, Curie], there’s nothing to accelerate. We put a man on the moon, but we knew it could be done when we started. The enormous accomplishment was making it happen. Dr. Fibiger goes on to say:
What the field lacks is sufficient basic knowledge about normal brain function and how its disturbance underlies the pathophysiology of psychiatric disease. Because of this, as the record now clearly shows, it remains too early to attempt rational drug design for psychiatric diseases as currently conceived. The most obvious solution here is expanded investment in neuroscience. By necessity, this will be driven primarily by the efforts of clinical and basic scientists in academic settings because industry no longer has the appetite or the resources to engage in such activities. It is worth emphasizing that industry is in the business of making drugs, knowledge sometimes being a fortuitous byproduct. Academia is in the business of generating knowledge, and knowledge is what is needed at present.
Of course he’s right. Of course we need to expand our knowledge of basic neuroscience and those mechanisms of disease that we can clarify in the process. And if what he calls "serendipitous clinical observation" comes along the way, so much the better. But we haven’t even adequately defined the targets – the diseases that neuroscience needs to help us understand. As he says:
A major barrier to progress is the current state of nosology in psychiatry. A new taxonomy is a prerequisite for meaningful progress. Today, few would argue that syndromes such as schizophrenia and depression are single, homogeneous diseases. And yet when it comes to clinical research, including clinical trials, both are still almost always treated as such. For example, studies continue to be published on the genetics of both of these syndromes despite the fact that there never will be a robust genetics of either condition as the nature and severity of specific symptoms are too heterogeneous across individuals to have any consistent genetic correlates. Similarly, while DSM conceptualizations of psychiatric disease may have utility in current clinical practice, when it comes to research, they too are a barrier to progress.
He goes on to discuss the NIMH initiative in that direction, the RDoC [Research Domain Criteria]. He likes the idea. I’m not competent to judge the details. But if it’s such a good idea, why didn’t they have it a long time ago? And I worry that the same people who have given us this recent past are still in charge. But beyond that, I wish them the best. These aren’t the kinds of things I personally need to weigh in on. I have something else to say.

I’m thinking of a couple of analogies. Our invasion of Iraq was a mistake of herculean proportions. It was conceived in the halls of a think-tank by a group then called the neoconservatives. We now live with the consequences, but have never really gone back and looked at how it all happened. To their credit, the British are doing that with something called the Chilcot Inquiry, accompanied by extensive public hearings. The report is due out in 2013. Their watchwords are "Lessons Learned." Our financial collapse of 2008 was the result of a complex bit of recklessness that had to do with the repeal of the Glass–Steagall Act allowing the derivatives market to thrive and the fatal commerce in packaged mortgages. We’ve failed to have an extensive inquiry into that debacle with "Lessons Learned" as the goal. Then looking way back to the question of War Neurosis in World War I that I briefly reviewed recently [badges 1…], there were comprehensive reviews on both sides of the War with "Lessons Learned" in mind.

If there were ever a situation where a retrospective examination aimed at "Lessons Learned" was indicated, the last thirty plus years of psychiatry and psychopharmacology would make the best of candidates. In Psychiatry, The Pharmaceutical Industry, and The Road to Better Therapeutics, Dr. Fibiger is candid that the outcome has been a failure, and he calls for more funding for neuroscience, asking academic psychiatry to pick up the torch that has been dropped by industry. He also calls for a new taxonomy in psychiatry as "a prerequisite for meaningful progress." He makes the excellent point that, "It is worth emphasizing that industry is in the business of making drugs, knowledge sometimes being a fortuitous byproduct. Academia is in the business of generating knowledge, and knowledge is what is needed at present." But, given the contemporary landscape, the distinction between industry and academia has been so indistinct that it’s difficult to see his suggestion as anything more than wishful rhetoric. And as for taxonomy, wasn’t the DSM-III revolution supposed to be the very kind of nosology he’s asking for? Isn’t that the point of the DSM-5 revision? Didn’t the DSM-III come from the last version of the Research Domain Criteria? With a thirty year history of academic psychiatry funded by and following after industry [and now in a collective funk at its exodus], we’d be a lot better placed to put our efforts into formally looking closely at how and why we got here. So what I liked about this article is that it clearly states that the massive experiment of the last thirty years has been a failure, and the critique of the folly in continuing the current trajectory is well framed. But what I don’t like are the same things I didn’t like about Dr. Insel’s version [Experimental Medicine] or the one from the American Foundation of Psychiatry’s recent Institute of Medicine Summit [APF Convenes Unique Pipeline Summit] or Dr. Nutt’s report [ECNP Summit on the future of CNS drug research in Europe]. They all see the crisis in drug development with its empty pipeline as the central problem and suggest ways to move ahead.

One of the over-riding characteristics of certain patients with personality disorders is that rather than having life crises that result in learning new skills, they have crisis lives. The frantic solution to the last crisis contains the nidus of the next one, simplistic and emotionally driven solutions quickly becoming the next problem. In the 1960s and 1970s, psychiatry had a crisis. Rather than carefully evaluating the state of things, fixing what needed fixing and holding on to what was useful, like our impulsive patients, we embraced a radical change that was based not on a bird in the hand, but on the two or more birds hypothesized as being in the bush just around the corner that weren’t really there. The neoKraepelinian tenet, The focus of psychiatric physicians should be on the biological aspects of illness, quickly morphed into something else – Mental Illness is biologic, and jumped over the kind of scientific clarity Dr. Fibiger longs for, actually diluting and obscuring the conditions that might have been appropriate targets for drug treatment and biological research, particularly in depression. That conceptual slide was a boon for the drug companies who were all too willing to bankroll academic psychiatry producing growing levels of corruption unprecedented in the annals of medicine and ultimately the trivialization of psychopharmacology altogether.

Psychopharmacology is not in crisis, though some psychopharmacologists seem to be beside themselves. But this part is true – "The data are in, and it is clear that a massive experiment has failed." But the failed experiment is much bigger than the one Dr. Fibiger addresses. Psychiatry has come to the end of a three decade long misadventure with multiple dysfunctional dimensions. This is hardly a time to declare that the absence of the still undiscovered drugs of the last three decades is anything like a crisis. Before we embark on yet another attempt to coerce science into giving us new agents and new directions, we need to comprehensively review how a movement that carried the banner of scientific revolution and a return to mainstream medicine wandered so far from the tenets and ethics of both. It’s time for a comprehensive examination of the last thirty years with a focus on "Lessons Learned"…
    July 29, 2012 | 10:01 PM

    Found this through Mad in America—former employee of FDA turned whistleblower


    If the FDA were to become an honorably scientifically aware watchdog and do what it’s supposed to do, researchers and psychiatric providers and researchers might be forced to actually face the music and act accordingly. Personally, as experimental as drug treatment actually is, I think anyone who prescribes should be required to report regularly to a central authority with all observations about a drug or drugs’ effects on a patient along with the reasoning for prescribing and changing prescriptions. That data should be freely available for research as a public property. The patients’ identity should be anonymous; but age, sex, and whatever relevant stats apply should be diligently reported.

    It makes no sense that patients are being told they need to stay on drugs for life while so few long-term studies of the effects of drugs and almost no studies on the effects of drugs combined are being done.

    Anyone who prescribes psychoactive drugs should be required by law to read to all patients the risks. All patients also should be made to understand that one in a hundred, for instance, is not an astronomical number, nor is one in a thousand; especially when the risk is death.

    Bernard Carroll
    July 30, 2012 | 10:17 AM

    As Dr. Fibiger says, “It is worth emphasizing that industry is in the business of making drugs, knowledge sometimes being a fortuitous byproduct. Academia is in the business of generating knowledge, and knowledge is what is needed at present.” We could add that commercial ventures are sometimes a fortuitous byproduct of the academic search for truth – but they are not the main objective. That is where the field went astray, beginning with the Bayh-Dole Act of 1982.

    Both parties lost out here. The pharmaceutical industry suffered, as Dr. Fibiger makes clear in his refreshing editorial. Academia also suffered – much of the fun went out of research because the disinterested pursuit of knowledge that can lead to serendipitous observations went out of favor, to be replaced in clinical research by “big science.” This model reached its dysfunctional apogee with STAR*D and the like on the one hand and with mindless academic CROs on the other hand, churning out the dubious studies that Dr. Fibiger decries.

    August 2, 2012 | 6:45 PM

    Just as Dick Cheney looked at the US economy from the perspective of the oil industry, Dr. Fibiger expresses the desires of the pharmaceutical industry: “Subsequent to his academic career, Dr Fibiger was Vice President of Neuroscience at Eli Lilly and Company, Vice President of Neuroscience at Amgen, and Senior Vice President and Chief Scientific Officer at Biovail Laboratories International.”

    Pharma would very much like academia and government funding to assume the labor and risks of drug development. If a discovery is promising, pharma can buy in and reap the profits, maybe structuring the deal so the public will bear part of the burden of paying off injury lawsuits.

    Yep, psychiatry will change, according to what the drug companies need. Even with more public money in research, the drug companies will fight government oversight so they can keep tame colonies of university researchers whose job will be to feed the “pipeline.” Clinicians will be of value only as distributors and it won’t matter if they’re specialists. New drugs will be found, inevitably, to be no better than old drugs. And so it goes. The only difference is that research will cost the taxpayers a lot more money, and corporations a lot less.

Sorry, the comment form is closed at this time.