» Why Psychiatry's Seismic Shift Will Happen Slowly
08/05/13 08:43 from Forbes - Tech
Last week, Thomas Insel, Director of the National Institute of Mental Health, published a blog post that outlined a new approach for deciding what psychiatry research the U.S. government would fund. No longer, he wrote, would the NIMH rely ..
Matthew Herper, Forbes Staff
I cover science and medicine, and believe this is biology's century.
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5/08/2013 @ 9:43AM |2,000 views
Why Psychiatry's Seismic Shift Will Happen Slowly
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Thomas R. Insel, Director, National Institute of Mental Health. (Photo credit: Wikipedia)
Last week, Thomas Insel, Director of the National Institute of Mental Health, published a blog post that outlined a new approach for deciding what psychiatry research the U.S. government would fund. No longer, he wrote, would the NIMH rely on the Diagnostic and Statistical Manual of Mental Disorders, the collection of symptoms used by psychiatrists to diagnose depression, bipolar disorder, schizophrenia, and other ailments, as its “gold standard” for categorizing patients in research studies. He wrote:
While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.
As a result of this, he wrote, the NIMH “will be re-orienting its research away from DSM categories.” Instead, it would be encouraging medical researchers to frame their studies using a still nascent classification system being developed by the NIMH, called RDoC.
The reaction from the blogosphere was swift and loud as journalists and bloggers interpreted the decision as a swipe against the fifth edition of the DSM (called the DSM-5) and the American Psychiatric Association, which compiles it. Mindhacks wrote that the NIMH was “abandoning the DSM” and called the move “potentially seismic.” New Scientist called it a “bombshell” and said the DSM was being “denounced.” The Verge also went with the headline that the NIMH was abandoning the “controversial bible” of psychiatry. John Horgan at Scientific American wrote that psychiatry was in crisis as Insel rejected its Bible and replaced it with nothing.
There were also some more nuanced comments, from Neurocritic and 1 Boring Old Man, noting that this was not a shift so much as a continuation of the line of thinking that had been presented previously by both Insel and the APA itself. But the DSM-5 has been beset by controversy, partly because Allen Frances, a prominent psychiatrist who worked on previous editions, has been publicly decrying the way the new edition of the manual was put together. And a fight between the country’s largest psychiatric organization and the institute that decides which psychiatric projects get government money was too good to pass up.
The real story is more complex, and it is driven by the huge disappointments of the past two decades in psychiatric research, which have failed to lead to new drugs and have led to most large drug companies backing away from or abandoning the psychiatric field. Changing how patients with mental illness are diagnosed is going to take a lot longer than many people seem to think. The DSM is not being abandoned — psychiatry is finally growing up.
I called the NIMH, and was put on the phone with Bruce Cuthbert, the director of the division of adult translational research. I had a pretty simple question. If the NIMH were really rejecting or abandoning the DSM, that would mean the agency wouldn’t accept studies that use DSM-5 criteria. For instance, if you wanted to test a new schizophrenia drug in schizophrenics, you’d have to find some new RDoC way of describing the disease.
Cuthbert said repeatedly that would not be the case. It’s not so much that studies that use the DSM-5 will be excluded and abandoned, but that researchers would now be allowed to apply for grants that would not use the manual’s diagnostic criteria, or subdivided them in new, creative ways.
“Using DSM diagnoses for research has become a de facto standard ever since the DSM-III came out in 1980,” Cuthbert said. “What we are trying to do is to study neural systems directly because they cut across lots of the dsm disorders.” I asked the question again. “We are moving in a new direction. That doesn’t mean that next month we’ll stop accepting DSM diagnoses. It rather is a shift in emphasis.
New studies can still include DSM diagnoses, but their boundaries should not be limited by what’s in the DSM. The new NIMH policy gives scientists the choice of going much broader, or being far more narrow.
In practice, grants at the NIMH are given out by a peer review scoring system in which anonymous experts critique proposals. At the end of the day, which grants get funded will depend on how they do in that system. So this change in focus will happen slowly, and will depend on the exact experiment being done.
The DSM-5 will still be the manual used by psychiatrists diagnosing patients, and it will still be used by insurance companies, and the government programs Medicare and Medicaid to decide what to pay doctors and hospitals for treating mentally ill patients. Cuthbert says that the NIMH is already working on ways to build “crosswalks” between the DSM-V and its new RdoC diagnosis system, which is still barely sketched out.
Why change at all? Cuthbert gives the example of one symptom of depression called anhedonia, the scientific name for inability to find pleasure in normally enjoyable activities. On the one hand, this condition occurs in lots of psychiatric illnesses, including anxiety and eating disorders. We don’t know if it is neurologically similar in all of them or not. On the other hand, there are different types of anhedonia, Cuthbert says. Some people might go out to dinner with friends and not enjoy it. Others might be so down as to lack the energy to get to the restaurant in the first place, even though they would enjoy it once they arrived.
The NIMH’s strategy with the RDoC approach is to dis-entangle a diagnosis like this. If there were a protein or blood test or brain scan that fit with one type of anhedonia (people with eating disorders who are too tired to go out for instance), but not with the others, it doesn’t want to miss it. But this means taking the DSM-5 apart and re-assembling it through arduous experimental work. “It’s going to take a decade or more for results to bear fruit,” Cuthbert says.
The idea that psychiatry needs to become more focused on biological causes of disease, not associations of symptoms, is not new, either for Insel, who gave a TEDex talk on the topic, or to psychiatry as a whole. A recent paper in The Lancet, a medical journal, found that schizophrenia, bipolar disorder, autism, major depression and attention deficit hyperactivity disorder all shared common genetic glitches as potential causes.
Behind all this talk about biology is a commercial reality: psychiatric drug development has become a dead-end. GlaxoSmithKline, Novartis, and AstraZeneca have stopped trying to invent new psychiatric drugs. Pfizer, Merck, and Sanofi have de-emphasized them. There are just 303 psychiatric drugs in development, compared to 3,436 cancer medicines and 1,247 drugs for other neurological disorders, according to the Analysis Group in a study commissioned by PhRMA, the drug industry trade group.
The introduction of the DSM-III in 1980 created a standardized language for psychiatry, and this did lead to big advances in psychiatric medicine. The next decade would see the introduction of anti-depressants like Prozac, Paxil and Wellbutrin and antipsychotic drugs like Zyprexa, Risperdal, and Abilify. In the 2000s, the NIMH funded big, independent clinical trials testing how well these medicines compared and how well to use them. A big study of the antidepressants found that a third of patients became symptom-free on taking them, but that switching those who were not helped to other drugs yielded diminishing results. A study of the schizophrenia drugs showed that, for just about all of them, patients and doctors chose to switch to another treatment three-quarters of the time, showing how difficult to use these medicines are.
But the strategy of conducting studies of existing drugs in thousands of patients fails when new drugs are not being invented. So Cuthbert says that the NIMH is very consciously focusing on small studies of new experimental drugs that drug companies have not embraced. The idea is to follow the “de-risking” model that has been successful for disease charities. The best example is Kalydeco, a drug for cystic fibrosis originally developed at Vertex Pharmaceuticals with funding from the Cystic Fibrosis Foundation. Eventually the drug became Vertex’s most important product, demanding lots of resources and generating a high price. The idea is to try to get industry interested in psychiatry again. Changing the diagnostic system, seen as one reason that drugs are failing, is part of the job.
Jeffrey Lieberman, the chairman of psychiatry at Columbia University’s College of Physicians and Surgeons, ran the NIMH’s big schizophrenia trial. He is also a defender of the DSM in its current form. But he is also a big believer that psychiatry needs to base its decisions more on biology, and less on behavior.
“The DSM is the past and, for the time being, the present,” says Lieberman. “But it won’t be the future. The future it will be either improved or replaced by a more physiologically based set of diagnostic criteria. That may change the whole landscape for diagnosis.”
