Federal Govt. Accused Of Abandoning Research That Would Provide Short Term Help To The Most Seriously Mentally Ill

Dr. E. Fuller Torrey rips into NIMH, its advisory board and NAMI

(6-8-20) Dr. E. Fuller Torrey is again accusing the National Institutes of Mental Health of virtually abandoning clinical trials that could help Americans with schizophrenia and bipolar disorder in the short term.

Instead, NIMH, the main federal government agency for research into mental illness with a budget of almost $2 billion, has made basic brain research its priority. The results of such research will take three or four decades to show results, if then.

What’s the difference between “clinical trials” and “basic research.”

Elizabeth Sinclair Hancq, the director of research at the Treatment Advocacy Agency, which Dr. Torrey helped found, provided examples for me in an email.

• Basic research: growing cells in petri dishes and testing the effect of a particular drug on cellular mechanisms, like stopping their growth or activity. Basic research also includes animal model studies when trying to understand underlying cellular or system biology.
• Clinical trials: Testing the effect of a particular drug on symptoms and disease processes.

Perhaps the best way to see the marked difference between the two is by looking at clinical trials the NIMH is not funding. TAC listed 16 examples in a press release all of which are listed at the end of this blog.

Here is a sampling:

• Efficacy of generic drugs: Psychiatric patients being switched from brand-name to generic psychiatric medications frequently complain about loss of efficacy. NIMH should support studies of generic drug efficacy for psychiatric illnesses.

• Long-term injectable antipsychotics: In recent years, several new long-term injectable antipsychotics have been introduced. Although each was approved by the FDA for being better than a placebo, almost nothing is known about their comparative efficacy against each other. NIMH funded trials on these medications would help physicians make more informed decisions on medications for their patients.
• Long term effects: Many of the psychotropic drugs commonly administered to millions of patients in the United States were only studied for their acute effects. Very little is known about the long-term effects of treatment with these medications regarding side effects, maintenance dose, and use of blood levels. These should be systematically studied. The results of such studies might enable treatment using doses which are lower than those currently used, reducing side effects and improving medication compliance.
• Duration of treatment: Current guidelines are not clear regarding how long patients should be treated after a first episode of psychosis. In practice, many clinicians recommend stopping after one year, often increasing risk of relapse. (Studies) should be done randomizing patients to continuation of low dose antipsychotic treatment 1, 2 and three years after their first psychotic episode, to see if continued treatment reduces risk of relapse, while monitoring side effects.
• ECT: Electroconvulsive therapy (ECT) is underused in the United States compared to other developed nations. Randomized, sham–controlled studies using modern research designs should be conducted in the United States testing the efficacy and safety of ECT. This might encourage the use of this unpopular, but safe and efficacious evidence-based treatment.

Dr. Torrey wrote that NIMH funding is now skewed with 90 percent going for basic research, versus a fifty-fifty split.

“Since NIMH is funded with taxpayer funds,” Dr. Torrey wrote in an email,  “people currently affected for psychiatric disorders should have some hope of benefiting from current research.”

In a 2016 article in the British Journal of Psychiatry, twenty current or former members of a blue ribbon panel that advises NIMH urged Dr. Gordon to fund both clinical and basic research, writing that both are essential.

This argument about funding between basic research and clinical trials began before Dr. Gordon took charge, as noted in an interview with Dr. Gordon written by Amy Ellis Nutt in 2017 in The Washington Post:

The debate heated up during the tenure of Gordon’s predecessor, Thomas Insel, who left the helm of the institute after 13 years. Insel emphasized neuroscience and urged a reshaping of how mental illnesses are classified. Rather than sticking with the long-used Bible of psychiatry, the Diagnostic and Statistical Manual of Mental Disorders, Insel endorsed an approach called RDoC, for Research Domain Criteria, which emphasizes research into genomic and brain imaging as well as behavior.

During that interview, Dr. Gordon acknowledged that both basic research and clinical trials have value, but he did not directly address Dr. Torrey’s or other scientists’ concerns about his choice of basic research over clinical trials. Nor could I find any explanation by him or NIMH on the Internet for the lopsided funding. (I will be happy to post one if provided.)

Dr. Torrey’s newest criticism comes in a co-authored article published in Psychiatric Times (see below,) TAC also has issued a letter/press release that criticizes the NIMH’s 2020 Strategic Plan for Research, noting that “The five-year plan is strongly weighted toward basic brain research to the exclusion of research that is of more immediate relevance for individuals who are currently affected.”

In that same release, TAC notes “except for one passing reference, the untreated individuals with serious mental illness who are homeless and incarcerated are entirely missing” from the 2020 plan.

In email exchanges with me, Dr. Torrey chastised members of the NIMH National Advisory Mental Health Council, who serve at the pleasure of NIMH, for not questioning Dr. Gordon and the funding shift away from clinical trials.

His harshest criticism, however, was aimed at the National Alliance on Mental Illness.

By contrast Mental (Health) Illness America has, to the best of my knowledge, never criticized NIMH research. For NAMI the situation is even worse. Two years ago, when we set out in article criticizing NIMH research, NAMI sent a notice later on the same day to all its chapters saying they should ignore our allegations because whatever NIMH is doing was fine with NAMI.

(Editor’s note: When this happened, I called a NAMI official and was told that NAMI agreed with the direction Dr. Gordon was taking NIMH.)

When I think of all the time spent in the 1990s by Jim and Carol Howe, Betsy and Dick Greer and others at Nami getting NIMH to focus on serious mental illness makes me sick to my stomach to realize how far Nami has fallen. It was Nami’s efforts in fact that persuaded Steve Hyman, then the NIMH director, to fund the CATIE trial which has been so useful in sorting out the first and second-generation antipsychotics. Steve funded the project not because he had any interest in it but rather just to get NAMI off his back.

As always, I welcome readers’ comments on my Facebook page.

Riches Abound, So Where Are the Trials for Schizophrenia and Bipolar Disorder?

From Psychiatric Times. Article by Drs. E. Fuller Torrey and Robert H. Yolken

Congress awarded the National Institute of Mental Health an additional $98 million as part of the National Institutes of Health budget resolution in December 2019, which brings the NIMH budget to just under $2 billion and represents a 35% increase since 2015, one of the largest increases in the history of the NIMH. Yet, during the 5 years from 2015 through 2019, NIMH funded a total of 2 new drug treatment trials for schizophrenia and bipolar disorder, according to clinicaltrials.gov. This contrasts with the 5-year period from 2006 through 2010 when NIMH funded 48 such trials. NIMH has thus almost entirely given up its role of evaluating drugs for the treatment of 2 disorders.

Schizophrenia and bipolar disorder are among the most serious psychiatric disorders and play a disproportionate role among individuals who end up homeless, incarcerated, and who commit suicide. The cost of schizophrenia alone in the US was estimated to be $155.7 billion, based on a 2013 study.¹ Traditionally, the pharmaceutical industry and NIMH have been the main developers of new psychiatric drugs. In recent years, the former has reduced its efforts to develop such drugs, at least in part because of the failure of genetic research to identify new targets for new drug development. Given the semi-withdrawal of the pharmaceutical industry, it would seem reasonable to expect the NIMH to increase, rather than decrease, its efforts.

A big part of the problem is the NIMH policy of requiring the identification of specific biological targets in the brain for treatment trials. This has been widely interpreted to mean that the NIMH is not really interested in supporting clinical trials at this time. Indeed, the NIMH has been widely criticized for focusing exclusively on basic brain research rather than clinical research that could help people currently affected by diseases such as schizophrenia and bipolar disorder. For example, in 2016, 20 current and former members of the NIMH National Advisory Mental Health Council published an editorial in the British Journal of Psychiatry criticizing the NIMH’s overemphasis on basic research.² Joshua Gordon, MD, PhD, the current NIMH director, has “acknowledged that neither genetic research nor the study of complex circuits was likely to produce new treatments anytime soon.”³

In fact, genetic findings relating to the immune system have been among the strongest genetic findings to date, and there is substantial genetic overlap between serious psychiatric disorders and a range of autoimmune diseases.^4,5 Findings from small studies indicating that immune modulatory drugs have promise for the treatment of schizophrenia and bipolar disorder should be followed with larger scale studies.⁶ In addition, there are neuro-hormones such as estrogen that are promising as well as probiotics and other agents to modulate the microbiome and gut-brain axis.^7,8 Given the fact that the last new psychiatric drug for psychosis was clozapine, which was approved 30 years ago, the time is long past due when the NIMH should undertake an aggressive search for better drugs. And now it has $2 billion in taxpayer funds to do so.

TAC Letter/ Press Release questioning NIMH’s 2020 plan.

2020 National Institute of Mental Health (NIMH) Strategic Plan for Research 

To whom it may concern:

The Treatment Advocacy Center appreciates the opportunity to provide comment on the National Institute of Mental Health (NIMH) draft 2020 Strategic Plan for Research.

The Treatment Advocacy Center is a national nonprofit dedicated exclusively to eliminating barriers to the timely and effective treatment of serious mental illnesses such as schizophrenia and bipolar disorder. Our organization promotes laws, policies, and practices for the delivery of psychiatric care and supports the development of treatments for and research into the causes of serious mental illnesses (SMI).

The National Institute of Mental Health (NIMH) is the main federal government agency for research into mental illness. The NIMH was authorized through the passage of the National Mental Health Act in 1946 to better help individuals with mental health disorders through better diagnosis and treatments. With a budget of almost $2 billion in 2020, the NIMH conducts research and funds outside investigators to better understand mental illness and develop new treatments to reduce the burden these disorders have on individuals.

Despite the NIMH’s vision that all mental illnesses should be prevented or cured, the NIMH has a history of ignoring those with the most severe mental illnesses, including markedly reducing treatment trials for medication treatments for schizophrenia in the last 15 years.

On December 2nd, the NIMH released a draft of its five-year plan for research and invited feedback from individuals and organizations. Again, it did not prioritize projects that will help those living with the most severe forms of mental illness, with little sense of urgency to improve the reality for those suffering right now and their families.

Missing People who are Homeless or Incarcerated: The NIMH five-year plan lists suicide prevention and early intervention in psychosis under the section on ‘Challenges and Opportunities,’ which lays the groundwork for their plan. However, except for one passing reference, the untreated individuals with serious mental illness who are homeless and incarcerated are entirely missing. At least one-third of the homeless, especially those who are chronically homeless and/or unsheltered, have serious mental illness. There are 10 times more individuals with serious mental illness in the nation’s jails and prisons than there are in state psychiatric hospitals. Untreated individuals with serious mental illness are also overrunning the nation’s emergency rooms and adversely impacting law enforcement in a variety of ways. The omission of this group under ‘Challenges and Opportunities’ suggests that NIMH does not regard them as a major problem to be considered for its research goals. The omission seems especially ironic given the fact that one week prior to the release of the NIMH draft research plan, the White House sent invitations for their upcoming White House Summit on Transforming Mental Health Treatment to Combat Homelessness, Violence and Substance Abuse.

Out of Balance: The five-year plan is strongly weighted toward basic brain research to the exclusion of research that is of more immediate relevance for individuals who are currently affected. Basic brain research, such as biological or animal-based research into how the brain works, is of course part of the NIMH mission. Some of these brain research initiatives, such as the Human Connectome Project, may well lead to new treatments 20 or 30 years from now. But the authors of the report appear to believe that understanding the underlying biological mechanisms of how the brain works is the overriding goal of NIMH research.

The imbalance in NIMH research has been confirmed by an analysis of its research portfolio and was pointed out in 2016 in an editorial published the British Journal of Psychiatry. Twenty current or former members of the NIMH National Advisory Mental Health Council noted that, in recent years, NIMH research has become increasingly centered on basic research, especially genetics and neural circuits, instead of research that might help people currently afflicted. In the editorial, they called for “an increase in public discussion of how to appropriate funding resources across mental health research domains.” The current NIMH draft report appears to further increase the imbalance toward basic research.

No New Treatments: According to the NIMH plan, no new treatments will be available until the distant future. The report assumes that the development of new treatments must await new research findings from basic brain studies. For example, Objective 3.1 states: “Develop new interventions based on discoveries in genomics, neuroscience, and behavioral science.” There is a total disregard of current research findings which could lead to better treatments if they were pursued. In addition, NIMH has almost completely stopped doing any treatment trials for serious mental illness using currently available drugs. For example, in 2018, the most recent year for which complete data is available, NIMH supported just one treatment trial for schizophrenia among its 2,640 total grants.

The following are examples of research initiatives on serious mental illness that are currently being under-researched or not researched at all by NIMH. Each study has the potential to lead to better treatments and/or the prevention of these disorders.

• Update of CATIE study: The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, funded by NIMH, compared more recently introduced antipsychotics with the older antipsychotics. The results, published in 2005, were extremely helpful in guiding the treatment of schizophrenia. Since that time, five new antipsychotics have been introduced. Doing a CATIE-type trial comparing the effectiveness of these medications would be very useful in guiding treatments.
• Efficacy of generic drugs: Psychiatric patients being switched from brand-name to generic psychiatric medications frequently complain about loss of efficacy. NIMH should support studies of generic drug efficacy for psychiatric illnesses.
• Long-term injectable antipsychotics: In recent years, several new long-term injectable antipsychotics have been introduced. Although each was approved by the FDA for being better than a placebo, almost nothing is known about their comparative efficacy against each other. NIMH funded trials on these medications would help physicians make more informed decisions on medications for their patients.
• Long term effects: Many of the psychotropic drugs commonly administered to millions of patients in the United States were only studied for their acute effects. Very little is known about the long-term effects of treatment with these medications regarding side effects, maintenance dose, and use of blood levels. These should be systematically studied. The results of such studies might enable treatment using doses which are lower than those currently used, reducing side effects and improving medication compliance.
• Duration of treatment: Current guidelines are not clear regarding how long patients should be treated after a first episode of psychosis. In practice, many clinicians recommend stopping after one year, often increasing risk of relapse. RCTs should be done randomizing patients to continuation of low dose antipsychotic treatment 1, 2 and three years after their first psychotic episode, to see if continued treatment reduces risk of relapse, while monitoring side effects.
• ECT: Electroconvulsive therapy (ECT) is underused in the United States compared to other developed nations. Randomized, sham–controlled studies using modern research designs should be conducted in the United States testing the efficacy and safety of ECT. This might encourage the use of this unpopular, but safe and efficacious evidence-based treatment.
• Medication compliance: Patients often do not come in to the clinic to receive long- acting injections. While in some cases this is due to active refusal of treatment, in many cases this is due to negative symptoms, disorganization and poor insight. Randomized studies showing that nurses who travel to patients’ homes and administer long acting injections once a month are predicted to show lower rates of treatment discontinuation and decrease in hospitalization.
• Disease markers: Clinicians are badly in need of accessible biological markers for the diagnosis and monitoring of treatment for psychiatric patients. NIMH should be collecting blood, saliva, and other accessible specimens from large groups of patients for population-based analytics.
• Infections in childhood: Several European studies have reported that infections in childhood are risk factors for the later development of serious mental illnesses. The studies need to be replicated in the United States with its more diverse population.

• Anti-inflammatory medications: Multiple studies have reported that serious mental illnesses have an inflammatory component. Sixteen different anti-inflammatory agents, some with promising results, have been tried for schizophrenia and/or bipolar disorder. NIMH is not currently supporting treatment trials for any of them but should be doing so.
• Probiotic treatment trials: Studies of the gut-brain axis and associated microbiome hold great promise for the development of new psychiatric medications. NIMH should be supporting treatment trials of probiotics and prebiotics for people with serious mental illness.
• Estrogen: Estrogen has been shown to be relevant to schizophrenia. There are well- replicated sex differences in the age of onset and disease course of schizophrenia that indicates that hormone differences between sexes might have an influence. Several randomized controlled trials administering estradiol patches to female patients with schizophrenia reported a beneficial effect. Further RCTs should be done, taking into account the risk for cancer, and the brain mechanism by which estrogen improves symptoms should be explored.
• Herpes viruses: Several studies have reported increased antibodies to various herpes viruses in individuals with schizophrenia and bipolar disorder. The viruses include cytomegalovirus, herpes simplex virus, Epstein-Barr virus, and others. Most recently, for example, aberrant immune responses to the Epstein-Barr virus were found in many individuals with schizophrenia and major depressive disorder. Studies of these viruses and the use of anti-viral medications could be very beneficial to those suffering from serious mental illness.
• Toxoplasmosis: Four studies have reported that cat ownership in childhood is a significant risk factor for later developing schizophrenia. Toxoplasma gondii is a parasite carried by cats and increased antibodies to this parasite have been reported in multiple studies of individuals with schizophrenia. Research on the role of this parasite and the development of drugs against it could lead to improved treatments.
• Urban risk: Multiple studies have shown that being born in, or raised in, an urban area doubles the risk of later developing a serious mental illness. Understanding the cause of this could lead to better treatments or even prevention of these diseases.
• Migrant risk factor: Multiple European studies have shown a dramatic increase in serious mental illness in individuals who migrate from one specific country to another, for example Jamaica to England or Morocco to the Netherlands. This is not true of all migrants but only specific groups. The increase in incidence of serious mental illness is as much as six-fold. Doing studies of these migrants could lead to understanding the cause and better treatments for these illnesses.In summary, the draft plan for NIMH research goals for 2020-2025 further exacerbates the existing imbalance in NIMH research. It offers little hope for new or better treatments for individuals who are currently afflicted with a mental illness during their lifetime, especially a serious mental illness. Like NIMH’s present research portfolio that includes only one treatment trial for schizophrenia among its 2,640 grants, the proposed 5-year research plan is completely unacceptable to individuals with severe mental illness and their families. It is also inexcusable given the large increase in research funding given to NIMH by Congress in recent years. Such funding should have been, and should be, used to correct the existing imbalance, not to further exacerbate it. Those with the most severe forms of mental illness deserve to be prioritized.

Sincerely,

Fuller Torrey, MD, Founder of the Treatment Advocacy Center and Associate Director for Research, Stanley Medical Research Institute

Michael Knable, DO, Board President, Treatment Advocacy Center and Medical Director, Clearview Communities

Robert H. Yolken, MD, Board Member, Treatment Advocacy Center, and Director of the Stanley Neurovirology Laboratory, Johns Hopkins University Medical Center

Cameron Quanbeck, MD, Board Member, Treatment Advocacy Center, Associate Medical Director, Cordilleras Mental Health Rehabilitation Center, San Mateo, California

Jeffrey L. Geller, MD, MPH, Board Member, Treatment Advocacy Center Elizabeth Sinclair Hancq, Director of Research, Treatment Advocacy Center John Snook, Executive Director, Treatment Advocacy Center