PM378. A reduced risk of severe hepatic outcome with paliperidone exposure in schizophrenia patients with viral hepatitis: a population-based retrospective cohort study

Objective: Many evidences suggested that impairment of glutathione-dependent system is observed in the brain of schizophrenic patients. GSH is an important substrate of glutathione peroxidase (GPx). It is recognized that selenium-dependent GPx (GPx-1) out of GPx isozymes provides a first line of defense against peroxides. Thus, we investigated in the present study a role of GPx-1 gene in schizophrenia-like psychosis induced by phencyclidine (PCP) in mice. Method: GPx-1 knock-out (KO)-, wild-type (WT)-, GPx-1 overexpressing transgenic (Tg)and non-Tg-mice were received PCP (10 mg/kg/day, s.c.) for consecutive 14 days. Novel object recognition-, forced swimming-, and social interaction-tests were performed 7 days after withdrawal from PCP. Behavioral sensitization to an acute challenge of PCP (3 mg/kg, s.c.) was also evaluated. We examined Nrf-2-dependent GSH-synthetic process in the prefrontal cortex and hippocampus. Result: PCP-induced behavioral side effects were more pronounced in the GPx-1 KO than those in WT mice, and they were less pronounced in GPx-1 Tg than those in non-Tg mice. Moreover, PCP treatment significantly reduced GSH level, and increased oxidative burdens in prefrontal cortex as compared to those in hippocampus. Treatment with PCP resulted in a significant increase in nuclear translocation of Nrf2, Nrf2 DNA binding activity, and γ-glutamylcysteine modifier subunit (GCLm) mRNA expression in WT or non-Tg mice. These inductions were not observed in GPx1 KO mice. Further, this Nrf-2 dependent GSH synthetic system was more pronounced in GPx-1 Tg than non-Tg mice. Conclusion: Our results suggest that GPx-1 gene is a potential protective factor in response to schizophrenia-like psychosis induced by PCP in mice [This study was supported by a grant (14182MFDS979) from the Korea Food and Drug Administration, Republic of Korea]. PM378 A reduced risk of severe hepatic outcome with paliperidone exposure in schizophrenia patients with viral hepatitis: a population-based retrospective cohort study Running title: Schizophrenia, severe hepatic outcome, and paliperidone Chun-Hung Chang,1,2,3 Shaw-Ji Chen,4,5,6 Chieh-Yu Liu7, Hsien-Yuan Lane1,2 * 1Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan, R.O.C. 2Institute of Clinical Medicine, China Medical University, Taichung, Taiwan, R.O.C.; 3Sunshine Psychiatric Hospital, Taichung, Taiwan, R.O.C. 4Department of Psychiatry, Mackay Memorial Hospital Taitung Branch, Taitung, R.O.C. 5Mackay Junior College of Medicine, Nursing, and Management, Taipei, R.O.C. 6Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, R.O.C. 7Biostatistical Consulting Lab, Institute of Nursing-Midwifery, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan, R.O.C. *Corresponding author: Hsien-Yuan Lane, Ph.D. 2, Yuh-Der Rd, Taichung 40447, Taiwan Institute of Clinical Medicine, China Medical University Tel: +886-422052121 extension 1073 Fax: +886-4-26202946 E-mail: chang763@ gmail.com E-mail: [email protected] Financial Disclosure: The authors have indicated they have no relevant financial relationships to disclose for this article. Conflicts of Interest: The authors declare that there is no conflict of interest. Contributor’s Statement: Chun-Hung Chang conceptualized and designed the study, database processing and drafted the initial manuscript. Shaw-Ji Chen, and Chieh-Yu Liu provided expert opinions and reviewed the final submitted manuscript. Hsien-Yuan Lane is in charge of this study, including applying the research database, conducting the data analysis and critically reviewed the manuscript, and approved the final submitted manuscript. Abstract Objective: Paliperidone exhibits protective effects for liver, but the association between paliperidone use and the risk of severe hepatic outcome in schizophrenia patients with viral hepatitis is unknown. This population-based study is aimed to assess the incidence and risk of severe hepatic outcome among schizophrenia patients with viral hepatitis who received paliperidone. Methods: Using a nationwide database, the Taiwan National Health Insurance Research Database, subjects who had first been diagnosed with schizophrenia between 2007 and 2013 were identified. The schizophrenia patients with viral hepatitis receiving paliperidone were designated as the paliperidone group. A 1:2 ratio was used to select age-, gender-, and indexyear -matched control without paliperidone use. Patients who had severe hepatic outcome before enrollment were excluded. The 2 cohorts were observed until December 31, 2013. The primary endpoint was occurrence of severe hepatic outcome including liver failure, liver decompensation, liver transplantation, and liver cancer. Results: Among 953 newly diagnosed schizophrenia patients with viral hepatitis, we identified 134 patients with paliperidone use, and 268 matched patients without paliperidone use between January 2007 and December 2013. Of the 402 patients, 22 (5.47%) suffered from severe hepatic outcome during a mean follow-up period of 6.639 years, including 2 (1.49%) from the paliperidone cohort and 20 (7.46%) from the control group. In schizophrenia patients with viral hepatitis, the Cox multivariate proportional hazards analysis showed that the risk decreased with paliperidone use 0.1938 (95% confidence interval (CI), 0.0802 to 0.4681; p = 0.0135). Conclusions: Paliperidone use was associated with a reduced risk of severe hepatic outcome among schizophrenia patients with viral hepatitis.Objective: Paliperidone exhibits protective effects for liver, but the association between paliperidone use and the risk of severe hepatic outcome in schizophrenia patients with viral hepatitis is unknown. This population-based study is aimed to assess the incidence and risk of severe hepatic outcome among schizophrenia patients with viral hepatitis who received paliperidone. Methods: Using a nationwide database, the Taiwan National Health Insurance Research Database, subjects who had first been diagnosed with schizophrenia between 2007 and 2013 were identified. The schizophrenia patients with viral hepatitis receiving paliperidone were designated as the paliperidone group. A 1:2 ratio was used to select age-, gender-, and indexyear -matched control without paliperidone use. Patients who had severe hepatic outcome before enrollment were excluded. The 2 cohorts were observed until December 31, 2013. The primary endpoint was occurrence of severe hepatic outcome including liver failure, liver decompensation, liver transplantation, and liver cancer. Results: Among 953 newly diagnosed schizophrenia patients with viral hepatitis, we identified 134 patients with paliperidone use, and 268 matched patients without paliperidone use between January 2007 and December 2013. Of the 402 patients, 22 (5.47%) suffered from severe hepatic outcome during a mean follow-up period of 6.639 years, including 2 (1.49%) from the paliperidone cohort and 20 (7.46%) from the control group. In schizophrenia patients with viral hepatitis, the Cox multivariate proportional hazards analysis showed that the risk decreased with paliperidone use 0.1938 (95% confidence interval (CI), 0.0802 to 0.4681; p = 0.0135). Conclusions: Paliperidone use was associated with a reduced risk of severe hepatic outcome among schizophrenia patients with viral hepatitis. PM379 Quality of Life in patients with schizophrenia or bipolar disorder receiving long-acting antipsychotics Shih-Ku Lin, Taiepi City Hospital and Psychiatric Center, Taiwan Abstract Objective: Long-acting injectable antipsychotic (LAI) provides a potential solution to overcome poor adherence to medication inObjective: Long-acting injectable antipsychotic (LAI) provides a potential solution to overcome poor adherence to medication in