PM398. Fluctuations in hallucinatory experiences within a day in relation to dopamine D2 receptor blockade with antipsychotics in patients with schizophrenia

s | 45 Abstract Objective: The present study aimed to evaluate the efficacy and tolerability of blonanserin compared with other antipsychotics in the management of patients with schizophrenia. Methods: A systematic review and meta-analysis of randomized controlled trials comparing blonanserin head-to-head with other antipsychotics in schizophrenia were conducted. Embase, PubMed, the Cochrane Library databases, Clinicaltrials.gov, and UMIN were searched up to December 2015. The risk ratio (RR) and standardized mean difference (SMD)±95% confidence intervals (CI) were calculated using random-effects models. Results: Results: Nine studies (total n=1,491) were identified (vs. risperidone [3 studies, n=775], vs. haloperidol [2 studies, n=572], vs. aripiprazole [2 studies, n=70], vs. amisulpride [1 study, n=56], and vs. paliperidone [1 study, n=18]). Comparing blonanserin with other pooled antipsychotics, there were no significant differences in the Positive and Negative Syndrome Scale (PANSS) total score (p=0.84), PANSS positive (p=0.94), PANSS negative (p=0.24), and PANSS general psychopathology subscale scores (p=0.48), and response rate (p=0.92). However, blonanserin showed greater efficacy in PANSS total and positive subscale scores compared with aripiprazole (SMD=-0.83, CI=-1.36 to -0.30, p=0.002 and SMD=-0.82, CI=-1.35 to -0.28, p=0.003, respectively). No significant differences were found in treatment discontinuation between blonanserin and other pooled antipsychotics (due to any cause: p=0.375, inefficacy: p=0.15, adverse events: p=0.75). Blonanserin was significantly lower risk of hyperprolactinemia (RR=0.64, CI=0.51 to 0.80, p<0.001) and was associated with significantly less blood prolactin increase (SMD=-0.57, CI=-0.86 to -0.29, p<0.001) than the other pooled antipsychotics. Blonanserin also caused significantly less fatigue (RR=0.71, CI=0.51 to 0.98, p=0.035) and greater use of antiparkinsonian drugs (RR=1.34, CI=1.12 to 1.62, p=0.002). Conclusion: Our results suggest that blonanserin has a more beneficial effect on total and positive symptoms than aripiprazole and that there are significant differences in the safety profile between blonanserin and other antipsychotics. Policy of full disclosure: K Hagi is an employee of Sumitomo Dainippon Pharma.Objective: The present study aimed to evaluate the efficacy and tolerability of blonanserin compared with other antipsychotics in the management of patients with schizophrenia. Methods: A systematic review and meta-analysis of randomized controlled trials comparing blonanserin head-to-head with other antipsychotics in schizophrenia were conducted. Embase, PubMed, the Cochrane Library databases, Clinicaltrials.gov, and UMIN were searched up to December 2015. The risk ratio (RR) and standardized mean difference (SMD)±95% confidence intervals (CI) were calculated using random-effects models. Results: Results: Nine studies (total n=1,491) were identified (vs. risperidone [3 studies, n=775], vs. haloperidol [2 studies, n=572], vs. aripiprazole [2 studies, n=70], vs. amisulpride [1 study, n=56], and vs. paliperidone [1 study, n=18]). Comparing blonanserin with other pooled antipsychotics, there were no significant differences in the Positive and Negative Syndrome Scale (PANSS) total score (p=0.84), PANSS positive (p=0.94), PANSS negative (p=0.24), and PANSS general psychopathology subscale scores (p=0.48), and response rate (p=0.92). However, blonanserin showed greater efficacy in PANSS total and positive subscale scores compared with aripiprazole (SMD=-0.83, CI=-1.36 to -0.30, p=0.002 and SMD=-0.82, CI=-1.35 to -0.28, p=0.003, respectively). No significant differences were found in treatment discontinuation between blonanserin and other pooled antipsychotics (due to any cause: p=0.375, inefficacy: p=0.15, adverse events: p=0.75). Blonanserin was significantly lower risk of hyperprolactinemia (RR=0.64, CI=0.51 to 0.80, p<0.001) and was associated with significantly less blood prolactin increase (SMD=-0.57, CI=-0.86 to -0.29, p<0.001) than the other pooled antipsychotics. Blonanserin also caused significantly less fatigue (RR=0.71, CI=0.51 to 0.98, p=0.035) and greater use of antiparkinsonian drugs (RR=1.34, CI=1.12 to 1.62, p=0.002). Conclusion: Our results suggest that blonanserin has a more beneficial effect on total and positive symptoms than aripiprazole and that there are significant differences in the safety profile between blonanserin and other antipsychotics. Policy of full disclosure: K Hagi is an employee of Sumitomo Dainippon Pharma. PM398 Fluctuations in hallucinatory experiences within a day in relation to dopamine D2 receptor blockade with antipsychotics in patients with schizophrenia Teruki Koizumi,M.Da,b, Takefumi Suzuki M.D,PhDa,c, Robert R.Bies, PharmD, PhDd,e,f, Bruce G.Pollock,MD,PhDd,h, Aki Endoa, Ai Ohtania, Masaru Mimura,M.D,PhDa, Hiroyuki Uchida,M.D,PhDa,d a. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan b. Department of Psychiatry National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba, Japan c. Department of Psychiatry, Inokashira Hospital, Tokyo, Japan d. Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, ON, Canada e. Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA f. Indiana Clinical and Translational Sciences Institute, Indianapolis, IN, USA g. Schizophrenia Division/Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, ON, Canada h. Department of Psychiatry, University of Toronto, Toronto, ON, Canada Abstract Objectives: Dosing schedule of antipsychotics has conventionally aimed at assuring constant delivery of the drug. However, there has been no study to examine fluctuation in positive symptoms within a day in relation to dopamine D2 blockade with antipsychotic drugs in patients with schizophrenia in their chronic phase of the illness, which was addressed in this study. Method: Patients with schizophrenia (ICD-10) who had auditory hallucination and were receiving monotherapy with risperidone or olanzapine were included. Subjects were asked to record the time, frequency, and duration during 8 time periods (i.e. 00:0003:00, 03:00-06:00, 06:00-09:00, 09:00-12:00, 12:00-15:00, 15:00-18:00, 18:00-21:00, and 21:00-24:00) for 3 days. Time and degree of peak and trough dopamine D2 receptor blockade with antipsychotics were calculated from 2 sparsely collected plasma drug concentrations for each subject, using our D2 prediction model. Frequencies and durations of auditory hallucinations were compared between the peak and trough time periods, using a paired t-test. Result: 21 patients have participated in this study as of 31st Jan 2016; the preliminary analysis included the data from 11 participants (11 inpatients; 7 men; age, 61.5 ± 9.2years; duration of illness, 36.4 ± 61.3 years; Positive and Negative Syndrome Scale total score, 70.2 ± 20.8). No significant difference was found in the frequency or duration of auditory hallucinations between the peak and trough time periods (frequency, 0.36 ± 0.50 vs. 0.45 ± 0.52; duration, 21.8 ± 30.3 vs. 27.3 ± 31.3 mins). A chisquared test revealed that auditory hallucination occurred most frequently during the time period of 18:00-21:00 at 63.3% (p=0.03) Conclusion: The results suggest that occurrence of auditory hallucinations was not related to dopamine D2 receptor blockage with antipsychotics within a day in patients with schizophrenia; rather, it seems to be associated with circadian rhythm. If this finding is confirmed in further investigations, it will have huge impact on the design of dosing schedule in the treatment of schizophrenia.Objectives: Dosing schedule of antipsychotics has conventionally aimed at assuring constant delivery of the drug. However, there has been no study to examine fluctuation in positive symptoms within a day in relation to dopamine D2 blockade with antipsychotic drugs in patients with schizophrenia in their chronic phase of the illness, which was addressed in this study. Method: Patients with schizophrenia (ICD-10) who had auditory hallucination and were receiving monotherapy with risperidone or olanzapine were included. Subjects were asked to record the time, frequency, and duration during 8 time periods (i.e. 00:0003:00, 03:00-06:00, 06:00-09:00, 09:00-12:00, 12:00-15:00, 15:00-18:00, 18:00-21:00, and 21:00-24:00) for 3 days. Time and degree of peak and trough dopamine D2 receptor blockade with antipsychotics were calculated from 2 sparsely collected plasma drug concentrations for each subject, using our D2 prediction model. Frequencies and durations of auditory hallucinations were compared between the peak and trough time periods, using a paired t-test. Result: 21 patients have participated in this study as of 31st Jan 2016; the preliminary analysis included the data from 11 participants (11 inpatients; 7 men; age, 61.5 ± 9.2years; duration of illness, 36.4 ± 61.3 years; Positive and Negative Syndrome Scale total score, 70.2 ± 20.8). No significant difference was found in the frequency or duration of auditory hallucinations between the peak and trough time periods (frequency, 0.36 ± 0.50 vs. 0.45 ± 0.52; duration, 21.8 ± 30.3 vs. 27.3 ± 31.3 mins). A chisquared test revealed that auditory hallucination occurred most frequently during the time period of 18:00-21:00 at 63.3% (p=0.03) Conclusion: The results suggest that occurrence of auditory hallucinations was not related to dopamine D2 receptor blockage with antipsychotics within a day in patients with schizophrenia; rather, it seems to be associated with circadian rhythm. If this finding is confirmed in further investigations, it will have huge impact on the design of dosing schedule in the treatment of schizophrenia. PM399 Attitudes toward antipsychotic long-acting injections among patients with Schizophrenia in Japan. Shuhei Kudo, Masamichi Isioka, Kazutosi Kubo, Shuhei Kudo, Yasusi Sato, Norio Sugawara, Norio Yasui-Furukori Hirosaki University University, Japan Abstract Aims: Long-acting injectable antipsychotics (LAIs) are an important therapeutic option for patients with schizophrenia. Despite good clinical evidence, namely the reduction of relapse ratesAims: Long-acting injectable antipsychotics (LAIs) are an important therapeutic option for patients with schizophrenia. Despite good clinical evidence, namely the reduction of relapse rates and duration of hospitalization, some clinicians believe that LAIs are unacceptable to patients due to injection site pain or constriction of the patients’ autonomy. The objective of this study was to assess the attitudes toward LAIs among patients with schizophrenia in Japan. Method: Using a cross-sectional design, we recruited patients with a DSM-IV diagnosis of schizophrenia who were admitted to three psychiatric hospitals from February to July 2014. The demographic data (age, sex, duration of education) and medical history of the subjects were obtained from their medical records. The Clinical Global Impressions-Severity of Illness (CGI-S) Scale and the Global Assessment of Functioning (GAF) were used to measure symptom severity and evaluate a patient’s general functions. We employed an original questionnaire specifically to survey patients’ andpsychiatrists’ attitudes toward LAIs. This study was approved by the Ethics Committee of the Hirosaki University School of Medicine, and all subjects provided written informed consent before participating in this study. Results: As a recognition of LAIs, psychiatrists thought that 39.0 (60/154) % of patients are “very suitable” or “suitable” for