Urgent Issues in Mental Health Now: An Expert Interview With Thomas R. Insel, MD

Thomas R. Insel, MD


May 16, 2008

Editor's Note:

On behalf of Medscape, Elizabeth Saenger, PhD, former Editorial Director, Medscape Psychiatry & Mental Health, interviewed Thomas R. Insel, MD, Director of the National Institute of Mental Health, about the current state of psychiatry and mental health in the United States. Dr. Insel explores where we have made the most progress in research and clinical practice and discusses the clinical challenges that must be addressed as the field progresses.

Medscape: Dr. Insel, as Director of the National Institute of Mental Health (NIMH), you are in a unique position to give us an overview of psychiatry and mental health in the United States today. Where have we made the most progress in research and clinical practice?

Dr. Insel: Progress in clinical practice has been most impressive in terms of treatment. Compared with when I trained some 30 years ago, we now have the ability to relieve the symptoms of most major psychiatric disorders, from schizophrenia to bipolar disorder to major depressive disorder, as well as most anxiety disorders. Those treatments fall largely into 2 categories: pharmacologic therapy and psychotherapeutic interventions, such as cognitive behavior therapy. Both categories of treatment have become more targeted and have proven effective, so we have made progress. In a nutshell, I would say we are at a point where most treatments get us better but not well. A series of recent studies have uncovered where we still have management difficulty, suggesting that while many available treatments have efficacy, perhaps they aren't as effective in the real world, for several reasons. First, medications are often discontinued by the people who actually could benefit from them. Second, many people don't actually get access to the care that would be most helpful. And third, some evidence-based treatments, particularly certain psychosocial interventions for schizophrenia and bipolar disorder that we know are helpful, are not provided widely enough to reach the people who most need them. So from a treatment perspective, what is perhaps most frustrating is that some of what we have learned through research and efficacy trials is actually not being used extensively; too many people with major mental illnesses are outside of the healthcare system and end up either in the criminal justice system or in other social services not immediately linked to good medical care.

Medscape: What can NIMH do to change this?

Dr. Insel: NIMH has 2 basic targets. One concerns the treatments we have now, which are good, but not good enough. We need to step back and understand more about the mechanisms and pathophysiology of these illnesses in order to develop a next generation of treatments that are far more effective. We have antipsychotic medications for schizophrenia that reduce the hallucinations and delusions, but people treated with these agents still don't go back to work. The reason for this is that schizophrenia is associated with cognitive symptoms and cognitive deficits that do not respond to current treatments. NIMH has recognized this as an important area for future medication development or cognitive remediation treatments that begin to help people with schizophrenia -- not only to have control over their hallucinations and delusions, but also to recover to an extent, allowing them to really participate in society and be gainfully employed. We need a new generation of research to be able to accomplish these kinds of goals, taking us from simply ameliorating symptoms to really facilitating recovery.

The second target has to do with optimizing currently available treatments. For instance, we know that in the treatment of depression roughly half of patients will respond to an antidepressant, such as an SSRI. Another group will respond to psychotherapy, such as cognitive-behavioral therapy. But what we don't know yet is who will respond to which treatment, and unfortunately we are in a situation of basically treating by trial and error. For example, someone can be on an SSRI for 8, 10, or 12 weeks before we recognize that it is not helpful. That is an awfully long time for someone with a very serious, often life-threatening illness to be on a medication without our knowing whether it is helpful. So what we would like to do is to develop a set of biomarkers and predictive tests to help us personalize treatment. In summary, the 2 main NIMH treatment targets are (1) developing new and more effective treatments, and (2) optimizing the use of current treatments.

Medscape: It sounds like psychopharmacogenetics?

Dr. Insel: Pharmacogenomics could be part of the way we personalize treatments, but so far it hasn't fully delivered on the promise that many of us had 5 or 10 years ago. I suspect that in terms of treating depression, schizophrenia, and autism, as well as other psychiatric disorders, we won't be dealing with a single genomic test, but rather a biosignature that includes clinical history, family history, perhaps a brain imaging result, as well as genomic data. Hopefully these factors will collectively help us to understand and predict who will respond best to which treatment.

Medscape: Where would you say that NIMH has made the best investments in terms of its funding and energy?

Dr. Insel: Identifying our best investments depends on how outcomes are measured. There are a number of places where I feel we've made big investments but are still waiting for the ultimate outcomes. We have already seen interesting results from the last 5- 6 years from our investment in large effectiveness clinical trials as opposed to the traditional efficacy trial. These large-scale practical trials involve 10,000 patients in 200 sites across the country, including primary care sites, private practices, and community mental health centers. These sites were selected to be what we would call "more real-world" kinds of settings, and to address how well current treatments work and for whom they work best. The studies, which go by a variety of acronyms, have focused on adolescents with depression, adults with major depressive disorder, chronic schizophrenia, and bipolar disorder; most are now complete and have generated highly informative results. We now have very good data showing that antidepressants, such as SSRIs, when combined with cognitive-behavior therapy, work very effectively in adolescents with depression, which was not as clear before this very large-scale trial was launched.

We also have data on the treatment of schizophrenia suggesting that some of the older, less expensive, antipsychotic medications should be considered as front-line treatments; in head-to-head comparison these agents appear to be roughly as effective as many of the newer and more expensive medications. We also have some very interesting results from studies of depression and bipolar disorder that help us to better understand which treatments are best for which patients and, in addition, how to proceed when initial therapy is unsuccessful. What is the next best choice? These are questions important to practitioners that previously we didn't have answers to; these are not the kinds of trials that pharmaceutical companies are likely to mount because they involve head-to-head comparisons between active medications, rather than comparing a medication with a placebo. So such investigations have been a large -- and, I believe, very effective -- investment.

I think the other major investment for us has been attempting to get a better handle on the basis of these disorders in the brain, in terms of both genetics and imaging. I suspect that if you look back 20 years from now and ask what were the most important developments in the 1990s and the first decade of the 21st century, in psychiatry it would be the reformulation of mental disorders as brain disorders. This is a rather slow and iterative process, but it is certainly truer in 2008 than it was in 1988. We have begun to recognize that each of these disorders, from autism, to schizophrenia, to mood disorders, to anxiety disorders, can be studied as a brain disorder involving specific brain circuits; usually these circuits include some part of the prefrontal cortex. We don't know fully where the circuits have gone astray, but we are increasingly reformulating the etiology of mental illnesses to involve altered development of brain connections. They may manifest much later in life, as with schizophrenia, which generally shows up around age 18 or older. But more and more we understand that though the manifestations may appear late, the underlying problem might be developing far earlier and affect the way brain connections form. We now think about major psychiatric illnesses as developmental brain disorders with the potential to be addressed through very early intervention.

Medscape: What are the most pressing issues that we face now in mental health in terms of not only research, but also preparing and attracting potential scientists to the field?

Dr. Insel: The challenges are at several levels; one entails having a workforce with the breadth and scientific expertise to understand major psychiatric illnesses as developmental brain disorders. However, we don't yet have all the tools to address this challenge. Even with the power of modern genomics and imaging, we still know just a small fraction of what we need to in order to predict and preempt these illnesses. So part of the challenge will be bringing in the next generation of scientists -- trained as both brain and clinical scientists -- to understand how we can have the greatest impact on psychiatric illness.

Another challenge in mental healthcare are the tremendous health disparities we struggle with in patients with psychiatric illness, a problem less frequent in neurological illness and other areas of medicine. It is fair to say that much of the mental healthcare still occurs outside the healthcare system. I would even point to something as rarified as a university environment, often harboring a counseling center in the same building as the campus health center. Students who present with schizophrenia, bipolar disorder, or major depressive disorder -- which we now think of in biomedical terms -- will most likely go to the counseling center, which likely has no communication with the student health center. This scenario symbolizes what we see in the whole community, where most people being treated for these disorders are outside the healthcare system. For example, bipolar illness is often misidentified, if identified at all, in those who are imprisoned, homeless, or recognized in school as having a disciplinary problem rather than a medical illness. So a major challenge ahead is helping the public, the medical community, and patient families understand that these are medical illnesses which shouldn't be attributed to personal weakness, or some mysterious force that can't be addressed in a typical hospital or clinic setting.

Medscape: Do you think this sort of thinking might be a legacy of the mind/body split, or is it related to something else?

Dr. Insel: Such thinking is partially due to 300 years of what we call Cartesian dualism, in which disorders of the mind are not considered disorders of the body or brain. The 1990s -- or "decade of the brain" --helped address this issue as we increasingly came to understand the association between the "mind" and "brain," or at least understand that mental events could be studied as brain events. An extension of this development is the understanding of mental disorders as brain disorders; however, this remains an evolving and incompletely understood process. I think it also must be recognized that psychiatry has played a large role in encouraging this attitude; for many years much of the psychiatry discipline has perpetuated the division between itself and medicine. In terms of my own education, we were essentially trained as a subdiscipline of psychoanalysis, with a very distant relationship to the rest of the medical school and with little emphasis on understanding these conditions as medical disorders. For example, we were taught in great detail that peptic ulcer disease was related to psychosocial stress. And the recognition today that this is a disease having to do with a specific, treatable bacteria reminds us that we need to be open to understanding mental or behavioral disorders within the realm of medical causes.

Medscape: Can you expand on the relationship between psychiatry and medicine?

Dr. Insel: Depression is an interesting example because it is highly prevalent, highly disabling, and even though the condition is imminently treatable, doesn't get treated often enough. If you ask nonpsychiatric physicians to characterize depression -- which is extremely common in private practice -- they will most likely be aware of Hollywood's interpretation of the illness, generally involving sadness, tearfulness, and perhaps hopelessness. But in fact for most men with depression, irritability or somatic complaints are more likely symptoms. Also, people don't recognize that depressed patients usually present to a private-practice office, not to a psychiatrist or community mental health center.

The morbidity and mortality associated with depression is only partly associated with suicide. For example, a person who suffers a myocardial infarction (MI) may have an increased risk for depression in the weeks after the MI, and we have come to learn that the presence of depression following an MI increases cardiovascular mortality approximately 2- to 3-fold. This is a greater risk for mortality from a cardiovascular event than is associated with almost any other cardiovascular variable, except, perhaps, being in cardiac failure; post-MI depression increases mortality risk more than the presence of an arrhythmia, the magnitude of the change in enzymes, or even infarct size. So obviously depression is not just a disease involving mood and cognition, but rather a condition affecting the whole body with implications for a wide range of medical disorders, including not only cardiac disease, but also immune conditions, cancer, and, as more recent data suggest, osteoporosis. Depression is a complex, physiologic event with numerous medical complications that need to be understood and appreciated if we're to focus on and succeed in treating the whole person.

Medscape: How do cultural factors affect the presentation of depression? And is there anything you would like to add to this discussion?

Dr. Insel: The cultural question is extremely important because America is changing so rapidly; we have to understand that depression may look different in people who grew up in other countries. NIMH has done some fascinating research investigating the risk for mental disorders in immigrants to the United States, showing that rates are actually higher in the next generation. So this sort of research has very important implications.

I think this issue of health disparities is especially critical. Our nation needs to understand the importance of providing treatment to people who need it most, but who may be least able to afford it. Part of what makes addressing mental disorders so difficult is that people with these conditions are often so disabled that they stop working, stop caring for their children, and may become homeless. Because so many of the costs associated with mental disorders are in the public domain, psychiatric illness is incredibly costly compared with other medical problems. Approximately 80% of antipsychotic prescriptions are paid through Medicaid or Medicare; there are really no other medical illnesses with this cost profile -- that is, with indirect costs such as social services and the cost that the public pays in both healthcare and nonhealthcare trumping specific medical costs. For example, in terms of psychiatric illness, the indirect costs of social services for issues such as unemployment, welfare, and aid to the homeless can be greater than for the healthcare itself. This is not the case for cancer, heart disease, or neurologic disorders. Thus we need to be thinking about how we treat psychiatric illnesses and develop therapies, not simply as a cost but as an investment; we pay tremendously for the care of people with mental disorders and are not doing so in a very efficient way.

Medscape: So you really have to look at the larger picture?

Dr. Insel: Absolutely. These are disorders that affect all of us and are extremely disabling. Besides just the emotional toll involved with mental illness, we also have to learn to effectively acknowledge and address the tremendous social costs.

This interview is published in collaboration with NARSAD, the World's Leading Charity Dedicated to Mental Health Research.