March 12, 2004

Meltzer’s study on ‘hot paper’ list

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Herbert Y. Meltzer, M.D.

Meltzer’s study on ‘hot paper’ list

Herbert Y. Meltzer, M.D., Bixler Professor of Psychiatry and director of the division of Psychopharmacology, has made Thomson Institute for Scientific Information’s “New Hot Papers in the field of Psychiatry/Psychology” list.

His study, “Clozapine treatment for suicidality in schizophrenia — International Suicide Prevention Trial,” was one of the most cited psychiatry/psychology publications during the past two months.

Meltzer’s paper is featured on their Web site, along with his comments explaining the significance of his study.

“This paper was the first controlled study to show that a drug treatment could reduce the risk of suicide attempts in patients with schizophrenia or schizoaffective treatment,” Meltzer told Thomson ISI. “At least 25 percent of patients with this illness make a serious attempt and at least 5 percent of them die by suicide. This study led to the FDA approving an indication for Clozapine to reduce the risk of suicide in these two disorders.”

Thomson ISI identifies the most cited researchers from 22 subject categories. Looking at the citations found in the footnotes or references in the hundreds of thousands of articles published in research journals every year, The organization compiles these citations and calculates which researchers have been cited most often. Among the various lists they publish, Thomson ISI reports the top papers every two months — New Hot Papers — that must have been published within the last two years and cited among the top one-tenth of 1 percent of all publications in their field.

“Since hot papers are very recent scientific contributions that are receiving recognition during a current period, they may signal important new trends in research and serve as leading indicators of scientific advance,” said Doug Benson, editorial assistant for Thomson ISI.

In his cutting-edge research, the study is the first to show that drug therapy alone could reduce the risk of suicide. It’s also the first study to lead to FDA approval of a drug to treat a symptom of schizophrenia beyond delusions and hallucinations.

“Before this, patients with schizophrenia were only treated with antipsychotics,” Meltzer said. “When the FDA gave this indication, it meant that one could look at components — suicidality or cognitive function, for example — and provide specific treatments.”

Clozapine, an antipsychotic drug, reduced suicidal behavior among people with schizophrenia or schizoaffective disorder by 26 percent compared to Zyprexia, a commonly prescribed antipsychotic drug.

“What’s interesting is that this research idea came from clinical observation, by taking care of patients,” Meltzer said. “I saw less controversies among those patients taking Clozapine.”

Meltzer began his research by conducting a mirror-image study, counting the suicide events of patients under the care of Clozapine as compared to their number of suicide events two years before. He found that of 100 patients, 25 had events in the two years prior to being treating with Clozapine, and only three had events while on Clozapine. Meltzer then rallied for support to conduct a controlled study.

Novartis, the drug company that makes Clozapine, sponsored a two-year study that included 1,000 patients in 11 countries.

“The study showed that at a 25 percent reduced risk for suicide, Clozapine could really save lives,” Meltzer said.

The FDA agreed, and reconsidered their approach to approving drugs for schizophrenia, allowing other elements of the disease to be separate targets for treatment. Meltzer hopes FDA approval and the popularity of his recent study will translate into clinical results.

“I’m working with HMOs and the Department of Mental Health in Tennessee to ensure clinicians bring Clozapine into their practice,” he said.

Meltzer is one of six Vanderbilt University School of Medicine faculty members that Thomson ISI considers a highly cited researcher — those among the 250 most cited researchers for their published articles within a specific time period.

The other five are: John H. Exton, M.D., Ph.D., professor of Molecular Physiology and Biophysics, professor of Pharmacology; F. Peter Guengerich, Ph.D., professor of Biochemistry, director of the Center in Molecular Toxicology ; Brigid L.M. Hogan, Ph.D., professor of Cell and Developmental Biology, Hortense B. Ingram Chair in Molecular Oncology; Tadashi Inagami, Ph.D., Stanford Moore Professor of Biochemistry, professor of Medicine, director of Specialized Center of Research in Hypertension and Grant R. Wilkinson, Ph.D., professor of Pharmacology.

Between 1991 and 1999, Meltzer was the ninth most cited researcher in schizophrenia and 12th in the field of psychiatry. He receives around 20 citations for every article he publishes.