1 Boring Old Man

I was looking around for some recent Tom Insel writing that was fully available on-line, and ended up at his Director’s Blog on the NIMH website. These are his December offerings with a plug for what’s coming next:

1. Antidepressants: A complicated picture _{[December 06, 2011]}
2. Treatment Development: The Past 50 Years _{[December 14, 2011]}
3. "In the next blog, I will suggest that what many are calling a ‘crisis in medication development’ may be an opportunity for NIMH innovation"

^{"We know that depression is a very heterogeneous syndrome." "A true understanding of the nature of these different forms of depression and the ability to predict who will benefit from the various treatments available depends on a better understanding of the biology of depression, either directly or indirectly through the use of ‘biomarkers.’"}

^{"As we engage ourselves in efforts to gain a deeper understanding of the biology of depression, it is important to remember that optimal treatment for depression does not begin or end with medication. Treating depression is an art that requires many tools. We will not save lives by dismissing any of the tools we currently have available, even as we endeavor to develop better ones. A quality treatment plan for depression includes a thorough assessment, a comprehensive treatment plan that includes choices tailored to and guided by the individual — whether that be medication, psychotherapy or both — and careful, frequent follow-up."}

This is the traditional picture of treatment development: public sector support of scientific discovery, and private sector investment in specific compounds and early phase clinical trials, followed mostly by private and some public funding of clinical trials. This traditional picture is about to change. NIH has announced plans to create a new institute—the National Center for Advancing Translational Science [NCATS]. Pending Congressional approval, NCATS should enable the development of innovative methods and technologies to enhance the development, testing, and implementation of diagnostics and therapeutics important for a wide range of human diseases and conditions, including mental disorders. NCATS would also support studies of the process of R&D, including a collaboration with the Food and Drug Administration to help identify barriers to progress and provide science-based solutions to reduce costs and the time required to develop new drugs and diagnostics. This should help reduce the “bottleneck” that occurs in the treatment development pipeline.

But change is coming from another direction as well, especially for psychiatric medications. Over the past year, several companies, including Astra Zeneca, Glaxo-Smith-Kline, Sanofi Aventis, and recently Novartis, have announced either a reduction or a re-direction of their programs in psychiatric medication R&D. Some of these companies [such as Novartis] are shifting from clinical trials to focus more on the early phases of medication development where they feel they can identify better targets for treating mental disorders. Others are shifting from psychiatry to oncology and immunology, which are viewed by some as lower risk.

There are multiple explanations for these changes. For instance, many of the blockbuster psychiatric medications are now available in inexpensive generic form. In addition, there are few validated new molecular targets [like the dopamine receptor] for mental disorders. Moreover, new compounds have been more likely to fail in psychiatry compared to other areas of medicine. Studying the brain and the mind has proven to be much more difficult than the liver and the heart. Most experts feel the science of mental disorders lags behind other areas of medicine. The absence of biomarkers, the lack of valid diagnostic categories, and our limited understanding of the biology of these illnesses make targeted medication development especially difficult for mental disorders.

Given the industry’s lack of innovation over the past three decades and the history of aggressive marketing of psychiatric medications, some might understandably say, “good riddance.” But by almost any measure we need better treatments, both medications and psychotherapies, for the entire range of mental disorders. It is never a positive sign for those with mental illness when thousands of scientists and millions of dollars are shifted away from research on these disorders.

What can NIMH do about this? Without the large budget and the scientific expertise for medication development, how can NIMH compensate for the pharmaceutical industry’s shift in focus? Is it appropriate for NIMH to invest public dollars in an area that many pharmaceutical companies have deemed too risky for investment? In the next blog, I will suggest that what many are calling a “crisis in medication development” may be an opportunity for NIMH innovation…

^{Translational science is a cross disciplinary scientific research that is motivated by the need for practical applications that help people. The term is used mostly in the health sciences and refers to things like the discovery of new drugs that directly help improve human health. Thus, translating bench science to bedside clinical practice or dissemination to population-based community interventions. In the United States, the National Institutes of Health have implemented a major national initiative to leverage existing academic health center infrastructure through the Clinical and Translational Science Awards.}

I’m sure that Tom Insel is not the right person to answer the question, "Is it appropriate for NIMH to invest public dollars in an area that many pharmaceutical companies have deemed too risky for investment?," or say "It is never a positive sign for those with mental illness when thousands of scientists and millions of dollars are shifted away from research on these disorders." Like the situation with Drs. David Kupfer and Darrel Regier and their DSM-5 revision, these are people who have spent their lives cheerleading the "up-side" of the DSM-III "Clinical Neuroscience" Psychopharmacology revolution while overlooking [or not seeing] its very tawdry under-belly. And they’re still riding the bus…

We await Dr. Insel’s proposals ["an opportunity for NIMH innovation"] with a very wary eye…