PT691. Haloperidol aggravates heart failure induced by pressure overload in mice through inhibition of sigma1-receptor

s | 51 who represented 3.8% of the entire claims for outpatient medical services in 2010.The measurement units used for psychotropic drugs were drug items and the number of defined daily doses (DDDs). Besides overall description, the data of psychotropic drugs were analyzed by stratifying patient’s age and chemical subgroup of antipsychotic drugs. Results: Prescription of psychotropic drug items (n = 1,868,092) was 2.5% of the total drug items (n = 74,348,407) claimed. The psychotropic drugs were prescribed to 27.4% of the total patients and in 9.9% of the total visits. Major consumers of psychotropic drugs were between 35–74 years of age and there were more women than men. The psychiatrists prescribed 48.8% of total DDDs of psychotropic drugs and contributed 33.5% of all drug items. The number of DDDs per 1000 inhabitants per day for all kinds of psychotropic drugs was estimated to be 61.4 in Taiwan, where anxiolytics accounted 17.8, hypnotics and sedatives 27.5, antipsychotics 4.6, antidepressants 7.8 and mood stabilizers 1.6. Ordered by total DDDs, the top 5 most frequently used antipsychotics were risperidone, quetiapine, sulpiride, haloperidol, and olanzapine. Conclusions: The usage level of psychotropic drugs in Taiwan was growing. Women were more inclined to use psychotropics than men. Anxiolytics and hypnotics contributed the major portion of psychotropic drugs. Atypical antipsychotics became the main stream of antipsychotic drugs but haloperidol keeps playing an important role clinically. PT690 Association between catecholamine metabolites after antidopaminergic intervention and mental condition in healthy subjects Tanja Veselinović 1,2* Holger Schorn 1,2, Uwe Henning3, Michael Paulzen 1,2 , Ingo B Vernaleken 1,2, and Gerhard Gründer 1,2 1Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany 2Jülich Aachen Research Alliance JARA, Translational Brain Medicine, Germany 3Neurobiochemical Research Unit, Department of Psychiatry, Heinrich-Heine-University, Düsseldorf, Germany Abstract Objective: Investigations of the association between the peripheral measurable catecholamine metabolites and the response toObjective: Investigations of the association between the peripheral measurable catecholamine metabolites and the response to antipsychotics and psychopathology in schizophrenia patients have shown incongruent results. Very little is factually known about their possible association with the general mental condition apart from specific psychiatric disorders. Methods: Catecholamine metabolites in plasma and 24h urine were determined in seventy-two healthy volunteers before and after 1-week administration of reserpine, aripiprazole, haloperidol or placebo in a randomized, single-blinded study. At the same time-points their mental condition was assessed using objective and subjective measures. Results: A significant increase of the concentration of the main metabolites of dopamine (homovanillic acid (HVA) in urine) and norepinephrine (3-methoxy-4-hydroxyphenylglycol in plasma as well as vanillyl mandelic acid concentration in 24h urine) occurred solely in the group receiving reserpine. The HVA plasma concentration measured after the psychopharmacological intervention correlated significantly with some clinical scores (PANSS total, PANSS negative, PANSS cognitive) in the total group of participants who received the antidopaminergic medication. There also was a negative correlation between the HVA levels and the subjective assessments of achievement potential, the ability to concentrate and the general well-being. On the opposite, for the self-assessment of exhaustion and apathy we found statistically significant positive correlations. Discussion: Altogether in our study solely reserpine caused a verifiable increase of some catecholamine metabolites probably as a result from the blockade of the vesicular monoamine transporter and the increased catabolism of monoamines by monoamine oxidase. Further the peripheral levels of monoamine metabolites were related to certain mental functions. Observed in healthy subjects, not affected by any psychiatric disorder, our results decouple this association from any specific pathological state, indicating a fundamental relationship. PT691 Haloperidol aggravates heart failure induced by pressure overload in mice through inhibition of sigma1-receptor Yasaharu Shinoda, Kohji Fukunaga, Hideaki Tagashira Tohoku University, Japan Abstract Haloperidol was commonly used for schizophrenia patients as D2 receptor antagonist. It has been known that haloperidol-induced cardiac sudden death is serious adverse event for schizophrenia patients. Haloperidol antagonizes not only D2 receptor but also σ1-receptor (σ1R), and we previously reported that σ1R stimulation ameliorates cardiac dysfunction by restoring mitochondrial Ca2+ mobilization in transverse aortic constriction (TAC) mice. In the cardiomyocytes, σ1R is associated with IP3 receptor in the sarcoplasmic reticulum (SR) and promotes mitochondrial Ca2+ mobilization from SR. Here we found that haloperidol impairs mitochondrial Ca2+ mobilization and promotes cardiac hypertrophy via σ1R inactivation in primary cultured cardiomyocytes. The σ1R inactivation by haloperidol also aggravated Ang II-induced impaired mitochondrial Ca2+ mobilization and ATP production. Inversely, σ1R agonist SA4503 ameliorated Ang II-induced impaired mitochondrial Ca2+ mobilization and ATP production. Our observations suggest that haloperidol promotes progression of heart failure via impairment of σ1R-induced mitochondrial ATP production.Haloperidol was commonly used for schizophrenia patients as D2 receptor antagonist. It has been known that haloperidol-induced cardiac sudden death is serious adverse event for schizophrenia patients. Haloperidol antagonizes not only D2 receptor but also σ1-receptor (σ1R), and we previously reported that σ1R stimulation ameliorates cardiac dysfunction by restoring mitochondrial Ca2+ mobilization in transverse aortic constriction (TAC) mice. In the cardiomyocytes, σ1R is associated with IP3 receptor in the sarcoplasmic reticulum (SR) and promotes mitochondrial Ca2+ mobilization from SR. Here we found that haloperidol impairs mitochondrial Ca2+ mobilization and promotes cardiac hypertrophy via σ1R inactivation in primary cultured cardiomyocytes. The σ1R inactivation by haloperidol also aggravated Ang II-induced impaired mitochondrial Ca2+ mobilization and ATP production. Inversely, σ1R agonist SA4503 ameliorated Ang II-induced impaired mitochondrial Ca2+ mobilization and ATP production. Our observations suggest that haloperidol promotes progression of heart failure via impairment of σ1R-induced mitochondrial ATP production. PT692 Pain, Anxiety and their relationship with Dose of Medications in Intensive Care Unit Sunyoung Park a, Jae-Seok Heo b, c, Jee-Seon Ahn b, Jin Young Parkb,* aDepartment of Psychiatry, Seoul Medical Center, Seoul, South Korea bDepartment of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea cProgram of healthcare & biomedical engineering, Seoul National University of Science and Technology, Seoul,