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(3-19-22) The debate about whether the National Institute of Mental Health should spend more of its $2 billion budget on clinical studies (behavior studies) versus pure brain research continues in today’s blog with NIMH critic Dr. E. Fuller Torrey claiming that NIMH Director Dr. Joshua Gordon recently misspoke during an interview with a New York Times reporter.
The New York Times’ story focused on Dr. Thomas Insel, former NIMH Director, and his new book, Healing: Our Path From Mental Illness To Mental Health, but it quoted both Dr. Insel and Dr. Gordon defending the agency’s dramatic shift away from clinical research.
That shift began under Dr. Insel’s leadership (he left NIMH in 2015). In the article, reporter Ellen Barry quotes Dr. Insel defending the move:
Dr. Insel…does not express regret about his work, or level any criticism at his successor at the N.I.M.H., Dr. Joshua A. Gordon, like him an advocate of basic research. If anything, Dr. Insel said, the country should “double down on brain research.”
The country’s mental health crisis is “not a research problem, it’s an implementation problem,” he said. Good treatments for serious diseases like schizophrenia and bipolar disorder already exist, he said, and it is not the job of scientists at N.I.M.H. to provide services.
“It has nothing to do with what they do,” he said. “It’s asking for French food from an Italian restaurant.”
The article further quotes Dr. Insel stating:
Dr. Insel…calls the advances in neuroscience of the last 20 years “spectacular” — but in the very first pages of his new book, he says that, for the most part, they haven’t yet benefited patients.
That comment didn’t sit well with his successor. In the article, Dr. Gordon reacted by saying:
Dr. Gordon, the current director of N.I.M.H., said Dr. Insel had failed to acknowledge “some really wonderful things that were done at N.I.M.H.” during his tenure or “the tremendous work that we continue to do in research that had short-term impacts on mental health care.”
He offered examples of two new treatments developed on the basis of neurobiological research: ketamine for treatment-resistant depression and brexanolone for postpartum depression. He said that the N.I.M.H. has also funded studies that led to treatments being used today, like a large-scale study that established the effectiveness of comprehensive services for people experiencing a first episode of psychosis.
As for the big breakthroughs, he said, they take decades to realize. Dr. Gordon was in graduate school when scientists cloned the gene for Huntington’s disease, and only now, three decades later, has that work led to new, effective treatments. To envisage breakthrough treatments in the short term, he said, was “bravado.”
Definitive treatments for autism, bipolar disorder and schizophrenia based on genetics are “not likely to pan out in the next five or 10 years,” he said. But researchers have identified hundreds of relevant genes and are “starting to understand the function of those genes in the context of the brain,” which could, he said, provide a pathway to better therapies.
“Could this be the same bravado?” he said. “I’m not using a date.”
Dr. Gordon’s statement, in turn, prompted this response from Dr. Torrey:
Why NIMH Claims Must Be Fact-Checked
Summary: Among four claims made by NIMH regarding psychiatric treatment, fact-checking established that 1 claim was true; 1 claim was true but incomplete; and 2 claims were not supported by the evidence.
On February 22 The New York Times published an important article regarding the mental illness crisis in this country (1). The author, Ellen Barry, interviewed Dr. Joshua Gordon, the director of the National Institute of Mental Health (NIMH) as part of her research.
In the article she cited four claims made by Dr. Gordon in his attempt to prove that NIMH has been doing “some really wonderful things” to improve the treatment of individuals with mental illnesses. Because some of Dr. Gordon’s claims appeared to be at odds with other published data, it seemed appropriate to fact check them. The results are as follows.
Claims #1 and #2: In the context of NIMH`s contributions, Dr. Gordon “offered examples of two new treatments developed on the basis of neurobiological research: ketamine for treatment- resistant depression and brexanolone for postpartum depression. “
Result of Fact Checking for Claim #1: False for ketamine
Ketamine was introduced in the 1960s as an anesthetic and has been widely used as such ever since. It has been known to block the NMDA class of glutamate receptors. In the 1990s research at multiple laboratories in the United States and Europe focused on the possible role of glutamate in causing depression. In the late 1990s researchers in the Department of Psychiatry at Yale University and the Connecticut Mental Health Center carried out the first trial using ketamine on depressed patients. The trial was funded by the Veterans Administration and published in 2000 (2). This was six years before the first NIMH study of ketamine was published (3). A history of ketamine confirmed the Connecticut group’s primacy for the human use of ketamine for depression (4). In 2019 Dr. Gordon himself had asserted that the development of ketamine was a result of “serendipitous clinical observations” rather than basic science research (5). Thus, NIMH cannot claim credit for introducing ketamine.
Results of Fact Checking for Claim #2: True but incomplete for brexanolone
In 2019 the Food and Drug Administration approved brexanolone, the first drug to be approved for the treatment of postpartum depression. The development of the drug was largely due to basic brain research on neurosteroids carried out in the 1980s in the NIMH Intramural Research Program (6). In his 2019 paper “From Neurobiology to Novel Medications: A Principled Approach to Translation” Dr. Gordon used this drug as a model for how future psychiatric drugs should be developed based on basic brain research (5). In his interview with the New York Times reporter he failed to mention that this process for brexanolone took 35 years.
Claim #3 Huntington’s Disease: “Dr. Gordon was in graduate school when scientists cloned the gene for Huntington’s disease, and only now, three decades later, has that work led to new, effective treatments.”
Result of fact checking for Claim #3: False.
Huntington’s disease is a simple, autosomal dominant disease caused by a variation in a single gene on chromosome four. The gene was successfully cloned in 1993 allowing work to begin on finding a treatment that would reverse the effect of the variation. The most advanced drug, tominersen, was developed by Roche pharmaceuticals and tested in a phase 3 treatment trial of almost 800 patients. The trial was stopped in March, 2021 because the patients receiving the drug did worse than those on placebo. Two other phase 1 trials related to the gene, sponsored by Wave Life Sciences, also had to be stopped because of poor results. There are at least two other phase 1 trials underway but the promised “new, effective treatments” are clearly a long ways off.
Claim # 4: Comprehensive Services “NIMH also funded studies that led to treatments being used today, like a large-scale study that established the effectiveness of comprehensive services for people experiencing a first episode of psychosis.”
Results of Fact Checking Claim #4: True
In 2008 NIMH funded two research grants that demonstrated that a team approach to treating early-stage psychosis was more effective than the usual individual practitioner approach. The program is known as the Recovery After Initial Schizophrenia Episode (RAISE) approach. These research grants were excellent examples of the kind of useful clinical research that NIMH should be doing. Under the directorships of Drs. Insel and Gordon such clinical research has been reduced from 50% to less than 10% of the total NIMH research budget (7).
Discussion
In the Internet era we have become accustomed to skepticism about claims being made online, and fact checking has become increasingly important. However, it is still surprising to find that two out of four claims made by the NIMH director to a New York Times reporter are clearly false, and a third is, at best, incomplete. It is understandable why Dr. Gordon would like to claim that ketamine`s development was a product of NIMH basic brain research and why he wishes that an effective drug for Huntington’s disease had been developed. Dr. Gordon has promised that basic brain research will lead to the development of new and better psychiatric drugs. The fact that he can only cite one such example, based on research done 35 years earlier, is embarrassing. Also embarrassing is the fact that there is still no effective treatment for Huntington’s disease despite the fact that the single gene for this disease has been known for thirty years. Theoretically the development of effective treatments for single gene diseases such as Huntington’s should be much easier than for diseases like schizophrenia that appear to be genetically much more complex. Wishing things were different, however, does not excuse the misstatement of facts. Dr. Gordon has a total staff of 1,462 individuals at NIMH (https://www.nimh.nih.gov/about/staff-directories/alphabetical-listing-of-all-staff) to help him keep his facts straight. We hope he will do better in the future.
References
- Barry, Ellen. February 22, 2022. The New York Times. “ The ‘Nation’s Psychiatrist’ Takes Stock, With Frustration”.
https://www.nytimes.com/2022/02/22/us/thomas-insel-book.html - Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351-354. doi:10.1016/s0006-3223(99)00230-9.
- Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856-864. doi:10.1001/archpsyc.63.8.856
- Li L, Vlisides PE. Ketamine: 50 Years of Modulating the Mind. Front Hum Neurosci. 2016;10:612. Published 2016 Nov 29. doi:10.3389/fnhum.2016.00612.
- Gordon JA. From Neurobiology to Novel Medications: A Principled Approach to Translation. Am J Psychiatry. 2019;176(6):425-427. doi:10.1176/appi.ajp.2019.19040386.
- Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 1986;232(4753):1004-1007. doi:10.1126/science.2422758.
- Torrey EF, Simmons WW, Hancq ES, Snook J. The Continuing Decline of Clinical Research on Serious Mental Illnesses at NIMH. Psychiatr Serv. 2021;72(11):1342-1344. doi:10.1176/appi.ps.202000739
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