a time for humility…

Posted on Tuesday 13 September 2011

I’ve made mention of the European College of Neuropharmacology that was meeting in Paris last week There’s a video presentation of a panel describing the goings on there now on their website that’s worth watching if you’ve got 30 minutes with nothing to do [Highlights 24th ECNP Congress]. Knowing that you’re unlikely to do that, here are the highlights of the highlights.

I’ve often teased about the signature beginnings and endings of papers that quote the statistics on the high burden of mental illness – "the World-Health-Organization-Public-Health plea for more biological research" I’ve called them. Well, the WHO statistics weren’t enough apparently, so they compiled the EU statistics. Bottom line? 38% of europeans are mentally ill now. Then there’s a major emphasis from everyone on very early intervention, quoting statistics that 75% of mentally ill people trace their symptoms to childhood. So the focus is on early treatment of ADHD and discussion of the "ultra high risk" groups for psychosis [from Dr. McGorry’s work?]. They seemed to dance around the issue of using drugs, the "ethical" questions of early treatment, by saying that those treated are "help-seeking" patients, people who are suffering. They too brought up the personalized medicine story, looking for genetic markers to predict drug responses.

If all of this is sounding very familiar, that’s the reason I’m mentioning it. It’s very similar to what our Drs. Insel [NIMH] and Kupfer [DSM-5] have been saying. There’s another similarity. Our NIMH is developing a research classification of sorts – RDoC [Research Domain Criteria] that is "based on dimensions of observable behavior and neurobiological measures." Well, the ECNP is doing a similar thing – in concert with the other colleges of neuropharmacology. Theirs is based on responses to drugs, neuroscience findings, etc. And they’re also thinking of doing something else – renaming drugs based on their mechanism of action. So instead of "anti-psychotic" we might say "Dopamine D2 Blocker."

This is, after all, the European College of Neuropsychopharmacology, so the focus is expected to be on drugs and treatment – the scientific aspects and the future. But while they do mention a few new drugs, much of what they discuss is new way to use existent drugs or drug classes – treat earlier, directed by genetic markers, etc. New drug treatments mentioned? Drug strategies directed towards targeting the negative symptoms in Schizophrenia.

Those of us who are not neuropsychopharmacologists have been primarily interested these days in the downside of drug treatment – lack of efficacy and toxicity – and the interference of the pharmaceutical industry itself in matters academic. For many, there’s an understandable backlash against pharmacotherapy altogether. I even found myself listening to this panel suspiciously – scanning for danger – rather than hopefully – looking for treatments that might help people with mental illnesses.

Trying to listen to all of this as a Pharmaceutical Executive, I think I’d be wary of throwing much muscle into psychiatry right now. I’m skeptical about the personalized medicine paradigm as it’s being pursued. It feels more like borrowed technology than something driven by a solid set of hypotheses. Why would we be genetically programmed to respond to one specific SSRI over another? There are too many other more likely explanations for the disappointing track record of the antidepressants. And while I’m emotionally drawn to the idea of early detection in Schizophrenia, I’m not convinced that it’s yet a clinical direction – more in the range of research hypothesis. So if I were a drug company czar, I’d be sitting this one out until someone comes up with something [which is apparently what they are doing].

As I said, I’m no psychopharmacologist, but I did have an interesting reaction watching the video and reading through the program. The only thing I saw about the Atypical Antipsychotics was a paper from the Hôpital Pitié Salpétrière cautioning about their use in children [bipolar children]. I realized that I was looking for research into what’s wrong with our current drugs. How do the SSRIs cause Akathisia? Why do people have withdrawal? Are these side effects part of the therapeutic effect? Why do people get the metabolic syndrome with Atypicals? Is it linked to any therapeutic effect? And why do they also have withdrawal?

So, "me too" drugs are OUT. Receptor hypotheses are tired, maybe passé. Targeting symptoms and subgroups is IN. "Early" is IN for Autism, ADHD, and Schizophrenia but OUT for Bipolar Disorders. Mostly, people seem to be looking for some new directions without finding very much quite yet. I found myself wishing they’d spend their time trying to clean up and clarify the indications for what we do have while they’re waiting around hoping for breakthroughs. I think this is what things must be like in the period Thomas Kuhn called paradigm decline or paradigm exhaustion – a lot of disillusionment and cynicism on the outside with a forced exuberance on the inside – trying to keep the dreams alive. Rather than expanding the base [38% mentally ill], they’d be better advised to shrink things down to the population they can treat effectively [and some of them actually seem to be trying to do that]. Paradigm decline is a time for humility, not cheerleading, but it doesn’t always seems to work that way eg Tom Insel.
    “We are at an extraordinary moment when the entire scientific foundation for mental health is shifting, with the 20th century discipline of psychiatry becoming the 21st century discipline of clinical neuroscience”…
    September 13, 2011 | 8:24 AM

    Instead of watching the video of the ECNP conference, I was watching the home videos of the Kennedy family. And wondering how on earth they were persuaded to have a frontal lobotomy on their beautiful daughter Rosemary who apparently had begun to have “outbursts of emotion”???? What snake oil salesman sold them that treatment? I know it landed her in an institution.

    September 13, 2011 | 9:18 AM

    I once read about her. She was not psychotic, more on the rebellious side. It was obviously not an “indicated” treatment. Now we would question whether if psychosurgery was ever indicated, but she didn’t even fit the criteria of those days. I think it can only be categorized as a travesty.

    September 13, 2011 | 2:50 PM

    Wow….I had no idea; I thought she was “mentally disabled” and a lobotomy was still a really bad treatment choice, but if nothing was really wrong with her???? Wow.

    September 13, 2011 | 6:01 PM

    Like candy for a baby: sure hope you’ve read Paul Thacker’s article in Forbes about Nemeroff. As I’ve previously posted, I just hate it when my husband is right (in this case, about the ethically challenged leadership at UM)

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