In the last post, I talked blithely about how Pharma had functioned as a sugar daddy to psychiatry in recent decades, and that’s frankly how many of us have come to see it. I can conceive of partnerships between academia and industry that might not become cesspools of stealth advertising and scientific corruption like the last two decades – but it would certainly have to be under a completely different set of ground rules than we’ve lived under during the current era. I hope the misadventures of this period continue to be exposed and that the lessons learned are chiseled in granite for the future. But that’s not the topic of the moment. The topic is the current idea of the NIMH becoming directly involved in new drug development and translational neuroscience as it’s currently being redefined.
First, I don’t accept the argument that new drug development in psychiatry is some kind of emergency now as compared to any other point in history. The following are examples from the literature of psychopharmacological evangelism used to explain this sense of urgency:
| Depression is one of the most prevalent and costly brain diseases. In the last major epidemiology study conducted in the United States, major depression had an overall lifetime prevalence rate of 17.1% (21% in women and 13% in men), and comparable figures have been obtained worldwide. These findings represent an increase of approximately 6% in the 15 years since the previous study… |
| Affective disorders account for considerable psychiatric morbidity (pain and suffering), but also significant disability and consequent loss of productivity. Depression has been estimated to be the second leading cause of disability worldwide, surpassed only by ischemic heart disease. Moreover, depression is often associated with comorbid psychiatric disorders, most notably anxiety disorders (panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive−compulsive disorder and post-traumatic stress disorder). The mean age of onset of depression has markedly decreased from the 40- to 50-year-old range noted several years ago to the 25- to 35-year range, and this phenomenon has been observed worldwide. Depression often goes undetected, especially in children, adolescents and the elderly. Mood disorders are associated with a significant risk for suicide, which remains one of the top ten causes of death in the United States and in many countries throughout the world. Depression is a major independent risk factor for the development of coronary artery disease and stroke, and possibly other major medical disorders. |
| Major depression is now recognized as a highly prevalent, chronic, recurrent, and disabling biological disorder with high rates of morbidity and mortality. Indeed, major depression, which is projected to be the second leading cause of disability worldwide by the year 2020, is associated with high rates of mortality secondary to suicide and to the now well-established increased risk of death due to comorbid medical disorders, such as myocardial infarction and stroke. Considerable strides have been made over the past 2 decades in the development of safe and efficacious antidepressants. |
| Depression is an illness that frequently starts early in life, tends to run a chronic course, and produces substantial disability. According to the World Health Organization, depression is the leading global cause of years of life lived with disability and the fourth leading cause of disability-adjusted life-years, a measure that takes premature mortality into account. Depression is not only widespread and common, it may be fatal; an estimated 90% of suicides are associated with mental illness, most commonly depression. There were nearly 30 000 suicides in the United States in 1999, almost twice the number of homicides. Suicide has become the third leading cause of death in individuals aged 15 to 24 years. |
| Despite efficacious and widely available antidepressants and psychotherapeutic interventions, the psychosocial and medical burden of depression is increasing. In fact, the World Health Organization projects that depression will continue to be prevalent, and by the year 2020, will remain a leading cause of disability, second only to cardiovascular disease. Although we do not know with certainty why rates and disability associated with depression are increasing, it is likely that this mood disorder continues to be remarkably under-recognized and under-treated. Depression frequently occurs in the context of chronic medical illness, and it is only relatively recently that the research community has turned its attention to the relationship between depression and chronic medical conditions. However, there is much work yet to be done. |
Four of these paragraphs were written by a paid medical writer, Sally Laden, in industry generated articles ghosted for key opinion leader guest psychiatrist authors. One was written by Dr. Tom Insel, Director of the National Institute of Mental Health. They sound the same whether they’re written as part of a stealth advertising campaign to sell more drugs or by the person in charge of setting our research policies.
Next, the pharmaceutical industry has produced a steady stream of drugs, primarily antidepressants and atypical antipsychotics, touted as breakthroughs or blockbusters, approved based on statistical rather than robust efficacy during a time of admitted diagnostic imprecision. The commercial success of these medications has not been matched by broad therapeutic gains, and the consensus is now that the notion of a march towards improved efficacy, safety, or scientific clarity over the period has been an illusion, in part maintained by the allure of future discovery. The highly motivated pharmaceutical industry has poured a ton of money into chasing the dream of new discovery with little to show for their efforts. They have an armada of marketers and an ocean of customers, yet they’re giving up because they haven’t been able to find a product to launch.
In general, publicly funded research has generated knowledge about the basic biology of mental disorders, leading to the identification of treatment targets that may be explored further by the private sector. For instance, NIMH funding has been essential for identifying the serotonin transporter as a target for the development of antidepressants and dopamine receptors as targets for antipsychotic medications. While public funding has built the scientific foundation for medication development, most medication research and development [R&D] has been the domain of the private sector.
What the field lacks is sufficient basic knowledge about normal brain function and how its disturbance underlies the pathophysiology of psychiatric disease. Because of this, as the record now clearly shows, it remains too early to attempt rational drug design for psychiatric diseases as currently conceived. The most obvious solution here is expanded investment in neuroscience. By necessity, this will be driven primarily by the efforts of clinical and basic scientists in academic settings because industry no longer has the appetite or the resources to engage in such activities. It is worth emphasizing that industry is in the business of making drugs, knowledge sometimes being a fortuitous byproduct. Academia is in the business of generating knowledge, and knowledge is what is needed at present…
In fact, this trend towards directed research has been growing in the NIMH for some time, in Insel’s NIMH. No more eggheads following their noses. You want a grant? Then it has to be in an area of interest, in the predefined direction of "bench to bedside." Insel’s recent directives just further constrict the researcher’s options. But the truth is, by everyone’s reckoning, we need eggheads, people thinking creatively outside the box about the basics. And Insel’s NIMH, already deficient in providing a base of basic neuroscience in part because grant money is so tied to specific practical areas, has decided to adopt the approach of industry which is already at the end of its rope? get into the new drug development business? adopt the style of the better financed industry scientists who’ve failed to generate the mythic magic bullets?
The mission of NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. For the Institute to continue fulfilling this vital public health mission, it must foster innovative thinking and ensure that a full array of novel scientific perspectives are used to further discovery in the evolving science of brain, behavior, and experience. In this way, breakthroughs in science can become breakthroughs for all people with mental illnesses.
Whatever happened to the NIMH Research Domain Criteria (RDoC) http://www.nimh.nih.gov/research-funding/rdoc/index.shtml ?
The draft Research Domain Criteria Matrix as reported by Neurocritic http://neurocritic.blogspot.com/2010/11/research-domain-criteria-for.html looks plenty stupid.