Astellas Pharmaceutical Inc.
Astellas Pharmaceutical Inc.
News Article | May 5, 2017
New York, NY, May 5, 2017 - An international group of experts has concluded that, for patients with schizophrenia and related psychotic disorders, antipsychotic medications do not have negative long-term effects on patients' outcomes or the brain. In addition, the benefits of these medications are much greater than their potential side effects. These findings, by Jeffrey Lieberman, MD, Lawrence C. Kolb Professor and Chairman of Psychiatry at Columbia University College of Physicians and Surgeon and Director of the New York State Psychiatric Institute, and colleagues from institutions in the United States, Germany, The Netherlands, Austria, Japan, and China, were published today in the American Journal of Psychiatry. Nearly seven million Americans take antipsychotic medications for the treatment of schizophrenia and related conditions. The medications are prescribed to alleviate the symptoms of psychosis and longer-term, to prevent relapse. In recent years, however, concerns have been raised that these medications could have toxic effects and negatively impact long-term outcomes. This view, if not justified by data, has the potential mislead some patients (and their families) to refuse or discontinue antipsychotic treatment. For this reason, the researchers undertook a comprehensive examination of clinical and basic research studies that examined the effects of antipsychotic drug treatment on the clinical outcomes of patients and changes in brain structure. "The evidence from randomized clinical trials and neuroimaging studies overwhelmingly suggests that the majority of patients with schizophrenia benefit from antipsychotic treatment, both in the initial presentation of the disease and for longer-term maintenance to prevent relapse," said Dr. Lieberman. Moreover, whatever side effects that these medications might cause are greatly outweighed by their therapeutic benefits. "Anyone who doubts this conclusion should talk with people whose symptoms have been relieved by treatment and literally given back their lives," Lieberman added. The studies also revealed that delaying or withholding treatment has been associated with poorer long-term outcomes. "While a minority of patients who recover from an initial psychotic episode may maintain their remission without antipsychotic treatment, there is currently no clinical biomarker to identify them, and it is a very small number of patients who may fall into this subgroup," said Dr. Lieberman. "Consequently, withholding treatment could be detrimental for most patients with schizophrenia." And while preclinical studies in rodents suggested that antipsychotic medications can sensitize dopamine receptors, there is no evidence that antipsychotic treatment increases the risk of relapse. While antipsychotic medications can increase the risk for metabolic syndrome, which is linked to heart disease, diabetes, and stroke, the study did not include a risk-benefit analysis. "While more research is needed to address these questions, the strong evidence supporting the benefits of antipsychotic medications should be made clear to patients and their families, while at the same time they should be used judiciously" said Dr. Lieberman. The paper is entitled, "The Long-Term Effects of Antipsychotic Medication on Clinical Course in Schizophrenia." The authors are Donald Goff, MD (New York University School of Medicine, New York, NY), Peter Falkai, MD, PhD (Ludwig-Maximilians-University Munich, Germany), Wolfgang Fleischhacker, MD, (Medical University of Innsbruck, Austria), Ragy Girgis, MD (Columbia University Medical Center), Rene M. Kahn, MD, PhD (University Medical Center, Utrecht, The Netherlands;), Hiroyuki Uchida, MD, PhD (Keiyo University, Tokyo, Japan), Jingping Zhao, MD, Ph.D. (Central South University, Chengsha, China), and Jeffrey Lieberman, MD (Columbia University Medical Center and New York State Psychiatric Institute). Dr. Goff has received research support from Avanir Pharmaceuticals, the National Institute of Mental Health, and the Stanley Medical Research Institute. Dr. Fleischhacker has received research support from Boehringer-Ingelheim, Janssen, Lundbeck, and Otsuka; he has received honoraria for serving as a consultant to and/or on advisory boards for Allergan, Dainippon-Sumitomo, GedeonRichter, Janssen, Lundbeck, Otsuka, Takeda, and Teva; and he has received speaker's fees and travel support from AOP Orphan, Dainippon Sumitomo, Gedeon Richter, Janssen, Lundbeck, Pfizer, Otsuka, and Teva. Dr. Girgis receives research support from Allergan, BioAdvantex, Genentech, and Otsuka. Dr. Kahn has received consulting fees from Alkermes, Forrest, Forum, Gedeon-Richter, Janssen-Cilag, Minerva Neurosciences, and Sunovion and speaker's fees from Janssen-Cilag and Lilly. Dr. Uchida has received grants from Astellas Pharmaceutical, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Meiji-Seika Pharmaceutical, Mochida Pharmaceutical, Novartis, Otsuka Pharmaceutical, and Shionogi; speaker's honoraria from Dainippon-Sumitomo Pharma, Eli Lilly, Janssen Pharmaceutical, Meiji-Seika Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Shionogi, and Yoshitomi Yakuhin; and advisory panel payments from Dainippon-Sumitomo Pharma. All other authors report no financial relationships with commercial interests. New York State Psychiatric Institute and Columbia University Department of Psychiatry (NYSPI/Columbia Psychiatry). New York State Psychiatric Institute (founded in 1896) and the Columbia University Department of Psychiatry have been closely affiliated since 1925. Their co-location in a New York State facility on the New York-Presbyterian/Columbia University Medical Center campus provides the setting for a rich and productive collaborative relationship among scientists and physicians in a variety of disciplines. NYSPI/Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. The Department and Institute are home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders and childhood psychiatric disorders. Their combined expertise provides state of the art clinical care for patients, and training for the next generation of psychiatrists and psychiatric researchers. Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.
Okubo S.,Takeda Pharmaceutical |
Okubo S.,Japan National Institute of Biomedical Innovation |
Miyamoto M.,Takeda Pharmaceutical |
Miyamoto M.,Japan National Institute of Biomedical Innovation |
And 11 more authors.
Toxicological Sciences | Year: 2013
Circulating liver-specific mRNAs such as albumin (Alb) and α-1-microglobulin/bikunin precursor (Ambp) have been reported to be potential biomarkers for drug-induced liver injury (DILI). We identified novel circulating liver-specific mRNAs and quantified them, together with the two previously reported mRNAs, in plasma from rats treated with various hepatotoxicants to validate circulating liver-specific mRNAs as biomarkers for DILI. Among six genes selected from the database, high liver specificity of apolipoprotein h (Apoh) and group-specific component (Gc) mRNAs were confirmed by reverse transcription (RT)-PCR and the copy numbers of these mRNAs elevated in plasma from rats treated with thioacetamide. Liver-specific mRNAs (Alb, Ambp, Apoh, and Gc) were quantified by real-time RT-PCR in plasma from rats with single dosing of seven hepatotoxicants. There were noticeable interindividual and intercompound variabilities in the severity of liver injury. The levels of four mRNAs increased almost in parallel and correlated with changes in the alanine aminotransferase (ALT) values and the hepatocellular necrosis scores at 24 h after dosing. It was noteworthy that the magnitude of the increases in mRNA levels was greater than that in the ALT value. Time course analysis within 24 h after dosing revealed that the timing of the increase was different among mRNA species, and the plasma levels of Alb and Gc mRNAs increased substantially earlier than the ALT values, suggesting that patterns of changes in circulating liver-specific mRNAs indicate the progression of liver injury. These results strongly support the reliability and usefulness of the four circulating liver-specific mRNAs as biomarkers for DILI. © The Author 2013. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Ikegai K.,Astellas Pharmaceutical Inc. |
Imamura M.,Astellas Pharmaceutical Inc. |
Suzuki T.,Astellas Pharmaceutical Inc. |
Nakanishi K.,Astellas Pharmaceutical Inc. |
And 11 more authors.
Bioorganic and Medicinal Chemistry | Year: 2013
Here, a series of C-glucosides with azulene rings in the aglycon moiety was synthesized and the inhibitory activities toward hSGLT1 and hSGLT2 were evaluated. Starting from the azulene derivative 7 which had relatively good SGLT2 inhibitory activity, compound 8a which has a 3-[(azulen-2-yl)methyl]phenyl group was identified as a lead compound for further optimization. Introduction of a phenolic hydroxyl group onto the central benzene ring afforded a potent and selective SGLT2 inhibitor 8e, which reduced blood glucose levels in a dose-dependent manner in rodent diabetic models. A mono choline salt of 8e (YM543) was selected as a clinical candidate for use in treating type 2 diabetes mellitus. © 2013 Elsevier Ltd. All rights reserved.