For someone who suffers from a mental illness, the chances for receiving effective treatment and recovering are better now than ever in human history. Incredible as this may sound, it is true. We currently can do more for patients with serious mental illnesses like schizophrenia, schizoaffective disorder and major mood disorders using a range of pharmacologic agents and psychosocial treatments than could any of our predecessors. Moreover, it seems clear to anyone who is in a position to know that the best is yet to come.
At the same time, it is clear to mental health care providers and consumers alike that our treatments have significant limitations, as the CATIE project and other studies have shown, and the delivery of mental health care can be improved. There are two strategies to advance the quality of mental health care that we can pursue. The first is doing more and better with our current knowledge and treatments for mental illness. The second is by pursuing scientific research and making use of future progress and breakthroughs.
Currently, we employ a range of pharmacologic agents and psychosocial therapies and services for the clinical care of patients with serious mental illnesses. However, as providers we do not or cannot avail ourselves of these treatments systematically or uniformly. Many of our medication practices are at variance with existing evidence and clinical logic. Most of our patients receive multiple medications in numerous combinations; a practice of polypharmacy for which there is little empirical basis. They also suffer from elevated rates of psychiatric and medical comorbidity, which may be contributed to, in part, by their medications. In addition, clozapine, the antipsychotic drug with proven superior efficacy, is greatly underutilized. Similarly, long acting injectable medications, which could be used to enhance treatment adherence, are only infrequently used.
Psychosocial treatments and services including case management, psychotherapy, cognitive remediation, social skills training, vocational rehabilitation, supported education and employment and assertive community treatment are not widely available, adequately reimbursed or uniformly applied.
Thus, it would seem that by utilizing currently available treatments and services more effectively we could realize substantial benefits for mental health care. However, we cannot overlook the fact that there are numerous and complicated systemic challenges to aligning treatments with evidence and configuring comprehensive services, not to mention the enormous difficulty of providing for their financing. In New York State we are fortunate to have outstanding leadership by the Office of Mental Health with initiatives underway to promote evidence-based services, prescribing practices and the use of electronic medical records. Consequently, clinicians and providers in New York State are positioned to lead the way in the effort to enhance the quality of mental health care and enable better outcomes for our patients.
Even with the optimal use of currently available knowledge, there will still be enormous unmet needs in the care of people who suffer with serious mental illnesses. We still do not know the causes of mental illness and have no diagnostic tests for them. Many patients are only partially responsive and some wholly unresponsive to existing treatments, and we lack treatments for many disorders (Alzheimer’s disease, autism) or aspects of disorders (e.g. negative symptoms and cognitive impairment in schizophrenia). And we certainly have nothing that approaches a cure for any mental illness.
Progress in these areas will require intensive scientific research. In this regard we are fortunate that the biomedical research enterprise that will inform psychiatric medicine and mental health care is burgeoning and gaining momentum. Brain disorders that express themselves through disturbances in mental functions and behavior are no longer being ignored by mainstream medical research. Of the broad array of research areas that bear on the understanding and treatment of mental illness, I would like to comment on two that are likely to transform the practice of psychiatric medicine and the way in which we provide mental health care in the immediate future.
The first is early detection and intervention research. In recent years, several lines of investigation have demonstrated the benefits of decreasing the duration of untreated illness and providing effective treatment early in the course of psychotic disorders like schizophrenia. This work has led to a passionate movement to develop early psychosis treatment programs around the world. The goal is to identify patients who are at risk for psychotic disorders or are experiencing early signs and symptoms of psychosis and to treat them before the full syndrome or the disabling effects of the illness develop. If implemented properly, early detection and intervention can limit the morbidity of psychotic disorders, prevent disability and foster recovery. This could save untold suffering and funds spent on services and disability.
However, there are two main problems that must be overcome to enable the early detection/intervention strategy to be successfully implemented. One is the lack of precise and reliable diagnostic criteria. The current approach identifies persons at “ultra-high risk” for a psychotic disorder using a combination of behavioral criteria along with family history. Even the best of these methodologies produces an unacceptably high false positive rate meaning that 40% to 70% of patients called high-risk cases will not develop a psychotic disorder in the ensuing three years. This means that people called high risk might be given an unwarranted diagnosis and possible treatment with its potential attendant side effects unnecessarily.
For this reason, it is imperative that we improve the diagnostic precision of our definition of high-risk persons. I believe that this will be done through the use of laboratory tests including genotyping, proteomic analysis, neuroimaging and electrophysiologic assessments. The NIMH has initiated major programs in the area of early detection/intervention. One, called NAPLS (North American Prodome Longitudinal Study) led by investigators at UCLA is a consortium of academic medical centers that are conducting research on the diagnosis and treatment of persons at high risk for psychotic disorders and in the prodromal phase of illness. The second is the RAISE project (Recovery After an Initial Schizophrenia Episode) the goal of which is to develop and test an optimal intervention program for patients with first episode psychosis that will limit disability and foster recovery. The lead sites for this ambitious project are in New York at Columbia University’s New York State Psychiatric Institute and the Zucker Hillside Hospital.
The other problem that must be addressed before the early detection/intervention strategy can be employed effectively is to determine the optimal therapeutic interventions. We do not know if antipsychotic drugs, which are used for the acute and chronic stages of the illness, should be used in the premorbid and prodromal stages as well. We do not know if the optimal interventions are pharmacologic or psychosocial. Therefore, better diagnostic methods and studies of therapeutic interventions are needed before this potentially transformative strategy will be ready for application in mental health care.
The second research area that will rapidly yield important benefits involves the practice of polypharmacy. Currently, polypharmacy is pervasive in mental health care with the vast majority of patients receiving multiple psychotropic medications. However, this practice, widespread as it may be, has little scientific basis and seems mainly born from efforts by clinicians to enhance the therapeutic response of patients by adding more drugs and trying new combinations. This is in large part due to the lack of progress in developing new drugs with novel mechanisms of action. In fact, the medications used for the psychotic and mood disorders are mechanistically pretty much the same as the prototypes that were developed over 50 years ago. However, several things have occurred in recent years that I believe will set the stage for the development of new drugs and new approaches to what can be called a scientifically based or rational polypharmacy.
The first development is that researchers and pharmaceutical companies have realized that there may not be a “magic bullet” for disorders like schizophrenia and bipolar disorder, which have multiple pathologic dimensions. Different pharmacologic actions may be required to remediate the distinct pathophysiologies that underlie the different symptom dimensions of the illness. Schizophrenia provides a good example. For almost a half-century, we have used drugs that block dopamine at the D-2 receptors to treat psychosis while searching for drugs that would also alleviate negative symptoms and cognitive deficits. However, we now know that the antipsychotic drugs whether they are first, second or third generation do not have any significant efficacy against negative and cognitive symptoms. Thus, the focus of drug development has shifted to targeting other systems than dopamine through the development of separate drugs that could be used as adjuncts to antipsychotics.
At the same time the FDA has sanctioned this approach by stating its willingness to approve drugs for indications such as cognitive enhancement and negative symptoms. Consequently, there is now a great deal of research activity underway to develop medications as adjunctive treatments that add to the therapeutic effects of antipsychotics.
The NIMH has helped to facilitate this process by their sponsorship of the TURNS program (Treatment Units for Research on Neurocognition in Schizophrenia). The purpose of this program comprised by eight academic medical centers and led by UCLA is to glean from the pharmaceutical industry promising novel compounds for cognitive enhancement and rigorously test them in phase II “proof of concept” studies. This program has been very successful and will be reporting out its results over the next year.
Ultimately, clinicians will be able to utilize multiple medications from different classes with different mechanisms of action to treat the various aspects of mental illnesses like schizophrenia and mood disorders in a way that is similar to what is done in managing cardiovascular disease.
Before concluding I would also like to comment on the ascendance of comparative effectiveness research as a priority in health care and for the U.S. government. For too long there has been no reliable source of information for clinicians to know how marketed treatments compared to each other and which are most effective and in which patients. Most clinical trials and comparisons of drugs are sponsored by the pharmaceutical industry, first to see they work at all in a given disease condition (phase II studies), then to gain FDA approval (phase III studies) and then in the post-marketing period to seek additional indications or in trials against competitors (phase IV studies). Due to concerns that there was not a source of objective and scientifically rigorous data about the comparative effectiveness of antipsychotic drugs the NIMH sponsored the CATIE Study (Clinical Antipsychotic Trials of Intervention Effectiveness) the results of which deflated many of the exaggerated claims about the superiority of the second generation antipsychotic drugs. In the wake of studies like CATIE, the federal government has mandated that a program in comparative effectiveness research be implemented and has allocated funds for this purpose. The exact means by which this research will be enacted and through what agencies it will be supported are not yet known but it will certainly come to pass within the next year. This will provide a means by which systematic evaluation of marketed medications can be carried out and made available to clinicians. This information will then guide the selection of treatments and their usage and combination. One example of the way that this type of information can be used is reflected in the form of a clinical care pathway called SHAPEMEDS that has been developed by the NYS-OMH and provides guidance to clinicians on medication selection, dose, efficacy, side effects, medical co-morbidity, adherence, and cost based on existing data.
With all the challenges that we face in providing mental health care to a diverse array of patients suffering from the major mental disorders, it is easy to see the glass as half empty rather than half full. However, I have no doubt that we have come a long way in the evolution of mental health care and already overcome the most difficult challenges. I firmly believe that the future is bright and will provide for a greater knowledge base about mental illness, capacity for their treatment and improving the quality of mental health care for generations to come.
Jeffrey A. Lieberman, MD, is a physician and scientist who has spent his career of over 25 years caring for patients and studying the nature and treatment of mental illness. Dr. Lieberman is currently is the Lawrence E. Kolb Professor and Chairman of Psychiatry at the Columbia University College of Physicians and Surgeons and Director of the New York State Psychiatric Institute. He also holds the Lieber Chair and Directs the Lieber Center for Schizophrenia Research in the Department of Psychiatry at Columbia and serves as the Psychiatrist in Chief of New York Presbyterian Hospital- Columbia University Medical Center. Dr. Lieberman received his medical degree from the George Washington School of Medicine in 1975. Following his postgraduate training in psychiatry at St. Vincent’s Hospital and Medical Center of New York Medical College, he was on the faculties of the Mount Sinai School of Medicine and Albert Einstein College of Medicine, and served as Director of Research at the Hillside Hospital of Long Island Jewish Medical Center. Prior to moving to Columbia University he was Vice Chairman for Research and Scientific Affairs in the Department of Psychiatry and Director of the Mental Health and Neuroscience Clinical Research Center at the University of North Carolina at Chapel Hill School of Medicine.
Dr. Lieberman’s research has focused on the neurobiology, pharmacology and treatment of schizophrenia and related psychotic disorders. In this context, his work has advanced our understanding of the natural history and pathophysiology of schizophrenia and the pharmacology and clinical effectiveness of antipsychotic drugs. In terms of the latter, he served as Principal Investigator of the Clinical Antipsychotic Trials of Intervention Effectiveness Research Program (CATIE), sponsored by the NIMH. His research has been supported by grants from the National Institutes of Health and the NARSAD, Stanley, and Mental Illness Foundations. His work has been reported in more than 400 articles in the scientific literature and he has edited or co-edited eight books, including the textbook Psychiatry, currently in its second edition; Textbook of Schizophrenia, Comprehensive Care of Schizophrenia; Psychiatric Drugs; and Ethics in Psychiatric Research: A Resource Manual on Human Subjects Protection. He also serves, or has served, as Associate Editor of the American Journal of Psychiatry, Biological Psychiatry, Neuropsychopharmacology, Acta Psychiatrica Scandinavica, Schizophrenia Research, Neuroimage, International Journal of Neuropsychopharmacology, and the Schizophrenia Bulletin.
Dr. Lieberman is a member of the National Academy of Sciences Institute of Medicine and recipient of the Lieber Prize for Schizophrenia Research from NARSAD, the Adolph Meyer Award from the American Psychiatric Association, the Stanley R. Dean Award for Schizophrenia Research from the American College of Psychiatry, the APA Research Award, the APA Kempf Award for Research in Psychobiology, the APA Gralnick Award for Schizophrenia Research, the Ziskind-Somerfeld Award of the Society of Biological Psychiatry, the Ernest Strecker Award of the University of Pennsylvania, the Lilly Neuroscience Award from the Collegium Internationale Neuro-Psychopharmacologicum for Clinical Research and the Exemplary Psychiatrist Award from the National Alliance of the Mentally Ill. He is or has been a member of the advisory committee for Neuropharmacologic and Psychopharmacologic Drugs of the Food and Drug Administration, the Planning Board for the Surgeon General’s Report on Mental Health, the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA), the APA Work Group for the Development of Schizophrenia Treatment Guidelines, the National Advisory Mental Health Council of the National Institute of Mental Health and currently chairs the APA Council of Research and Quality Assessment.
He resides with his wife and two sons in New York City.
