NEW HOT PAPERS - 2008

 Why do you think your paper is highly cited?

I believe the main reason this paper is highly cited is because it reveals a serious, even shocking, neglect of the physical health of millions of individuals suffering from chronic schizophrenia, a disabling psychiatric brain disorder.

The data in this paper, based on the landmark NIMH-funded CATIE study (Clinical Antipsychotic Trials of Intervention Effectiveness) provide an explanation for the tragically high early mortality in schizophrenia (a loss of 28 years of potential life, according to a recent study of several states), predominantly from cardiovascular disease. By pointing to the sad disparity of care in this seriously mentally ill population, steps can be taken to address the problem and reduce morbidity and mortality.

 Does it describe a new discovery, methodology, or synthesis of knowledge?

The CATIE study is the largest controlled effectiveness study of schizophrenia ever conducted. Because it enrolled "real world" patients, with medical comorbidities, substance abuse, and tardive dyskinesia (all of whom are excluded from the usual FDA efficacy studies), the study provided data about the prevalence, and treatments of various medical illnesses that real-world, community-based schizophrenia patients suffer from.

A high prevalence of the metabolic syndrome (42.7%) was found in this sample that represented 57 treatment settings around the US. In addition, we discovered that a significant proportion of the serious metabolic disorders that patients with schizophrenia suffered from (such as diabetes mellitus, hypertension, and hyperlipidemia) were not being treated for these illnesses at all, despite the wide availability of standard treatments of those conditions in the general population. Thus, the paper was the first to provide an actual measurement of the percentage of patients not receiving any treatment for several serious metabolic disorders that increase the risk of heart attacks and strokes.

Would you summarize the significance of your paper in layman’s terms?

The American people would find it very disheartening that many young men and women (average age about 39 years) suffering from schizophrenia and receiving psychiatric treatments in outpatient settings throughout the US. were not receiving any physical exams or lab tests to diagnose their medical conditions which would lead to effective treatment.

Thus, 30% of those with diabetes, 60% of those with hypertension, and 90% of those with high cholesterol or triglycerides had never received any treatment for their illness, although such treatments are widely available. Since these conditions often lead to early death from heart disease or stroke, such a lack of treatment has grave consequences for this population of persons suffering from schizophrenia, and significantly contributes to their high and premature mortality before they reach the age of 50.

How did you become involved in this research and were there any problems along the way?

I became involved in this research as one of the investigators in the CATIE study, which started almost 10 years ago, in 1998, under the overall leadership of Dr. Jeffrey Lieberman (see also), the Lawrence E. Kolb Chairman of Psychiatry at the Columbia University College of Physicians and Surgeons and Director of the New York State Psychiatric Institute.

The topic of this paper was not even on the radar screen back during the planning stages, because the main initial purpose of the CATIE study a decade ago was to compare the effectiveness of the old and new antipsychotic drugs (as measured by the percent of patients who discontinue the medication they are assigned due to efficacy, tolerability, safety, or personal choice reasons).

When the CATIE study approached completion, workgroups were assembled to analyze different components of the huge CATIE database. Because of my research interest and previous publications about obesity, diabetes, and increased lipids associated with some antipsychotic drugs, I chose to join the metabolic workgroup in 2004—the co-authors on my paper are the other members of that workgroup, which has been collaborating for the past four years on analyzing metabolic data in the CATIE.

By examining the tens-of-thousands of pieces of information coded on the 1,460 subjects enrolled in the CATIE study between 1999 and 2004, we were able to test many hypotheses and to glean highly relevant metabolic and cardiovascular risk data. We did encounter some challenges such as missing data or patients who were not fasting when their blood was drawn, problems that often occur in outpatient studies of the seriously mentally ill. However, those problems are minor compared to the tremendous amount of unique and clinically useful information that the CATIE database is providing.

Where do you see your research leading in the future?

The research in this paper will certainly lead to a vigorous examination of how persons with severe mental illness are treated for their non-psychiatric medical problems, such as obesity, diabetes, hypertension, and hyperlipidemia. Much research is warranted in this area because persons with schizophrenia are not only at risk for metabolic disorders due to lifestyle reasons (sedentary, poor diet of high fat/high calories, smoking, drug abuse, etc.), but they are also at risk of developing metabolic complications as a result of treatment with some of the widely used second-generation antipsychotic drugs.

Another avenue of future research is to test innovative models of comprehensive care for schizophrenia, with a collaborative model of care linking psychiatrists and primary care providers to ensure 360° of medical attention for the mind and the body. Such research may reduce the alarming morbidity and mortality that currently exists among those afflicted with serious mental disorders such as schizophrenia.

Do you foresee any social or political implications for your research?

Yes. This line of research straddles the biomedical and health services domains, and has political, social, and legal implications. Clearly, the findings of this paper from the CATIE study will prompt a serious examination of the current healthcare delivery model for serious mental illness. The presidential commission of the mental health system in the US described the system as "broken" for a variety of reasons that do not even include the devastating implications of lack of medical assessment and treatment of the patients in the system.

Clearly, current outpatient practices must be changed to protect patients from cardiovascular disease and premature death, not just to help them avoid psychotic relapses. The VA system is a good example of a "best-practice" for this area of clinical care because it mandates that every mentally ill veteran must have a primary care provider who conducts an annual physical exam and laboratory tests, and also provides medical management as needed.

Policymakers and legislators as well as health administrators and medical directors should all join hands to ensure that basic medical care is provided for people with schizophrenia and other serious mental disorders. Finally, I hope that psychiatrists in the US would be prompted by the findings of this paper to make sure that every patient they treat has access to not only the standard psychiatric care, but also to standard medical care as well.

Henry A. Nasrallah, M.D.
Professor of Psychiatry and Neuroscience
Department of Psychiatry
University of Cincinnati
College of Medicine
Cincinnati, OH, USA

Keywords: catie schizophrenia trial, hypertension, diabetes mellitus, hyperlipidemia, early mortality, medical comorbidities, substance abuse, tardive dyskinesia, community-based schizophrenia patients, dr. jeffrey lieberman, metabolic data, psychotic relapses.