New schizophrenia treatments may be effective for subgroup of patients

December 08, 2015

Philadelphia, PA, December 8, 2015 - Mounting evidence indicates that disturbances in the brain's glutamate pathway contribute to symptoms of schizophrenia. Thus, the glutamate pathway has become the target of a number of new drug therapies. Findings published in the journal Biological Psychiatry suggest that at least one of these drugs may be an effective treatment for individuals in the early course of the illness.

Re-analyzed data from inconclusive clinical trials of a compound called pomaglumetad methionil suggest that a more targeted population of subjects--patients who are early-in-disease or patients who have not already been exposed to other antipsychotic medications--may have produced a statistically significant response.

The authors of the current study hypothesize that these previous trials may have inadvertently selected subjects who would be nonresponsive to the medication and conclude that future efficacy trials may require the identification of subgroups of patient populations.

"The complex pathophysiology of schizophrenia and resultant patient heterogeneity present significant challenges to developing new and effective therapies for this disorder," said corresponding author Dr. Bruce Kinon of Lundbeck LLC. "Receptor selective compounds such as pomaglumetad may target specific sites that mediate disease in some but not all patients. Our tentative, though testable, findings may provide a direction for the development of personalized treatments for a patient subgroup whose illness is associated with a dysregulation of brain glutamate function."

"As we develop drugs that work by targeting the primary brain pathology in schizophrenia, it is likely that the differences between patients are going to play a bigger role in determining optimal treatment," commented Dr. John Krystal, Editor of Biological Psychiatry. "Kinon and his colleagues present interesting data suggesting that although pomaglumetad methionil does not work for all patients, it may be helpful for patients early in their course of illness or who have not had extensive prior treatment with a second generation antipsychotic medication or other serotonin-2 receptor antagonist."
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The article is "Exploratory Analysis for a Targeted Patient Population Responsive to the Metabotropic Glutamate 2/3 Receptor Agonist Pomaglumetad Methionil in Schizophrenia" by Bruce J. Kinon, Brian A. Millen, Lu Zhang, and David L. McKinzie (doi: 10.1016/j.biopsych.2015.03.016). The article appears in Biological Psychiatry, Volume 78, Issue 11 (December 1, 2015), published by Elsevier.

Notes for editors

Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact J. Scott MacGregor at jsmacgregor@lilly.com or +1 317 440 4699.

The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 6th out of 140 Psychiatry titles and 10th out of 252 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2014 Impact Factor score for Biological Psychiatry is 10.255.

About Elsevier

Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions -- among them ScienceDirect, Scopus, Elsevier Research Intelligence and ClinicalKey -- and publishes over 2,500 journals, including The Lancet and Cell, and more than 33,000 book titles, including a number of iconic reference works. Elsevier is part of RELX Group plc, a world-leading provider of information solutions for professional customers across industries. http://www.elsevier.com

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