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Yamaguchi J, Sadahiro R, Hirayama T, Wada S, Nakahara R, Matsuoka H. Severe behavioral and psychological symptoms of dementia successfully treated at home with a blonanserin transdermal patch: A case report. Neuropsychopharmacol Rep 2024; 44:474-478. [PMID: 38558544 PMCID: PMC11144598 DOI: 10.1002/npr2.12434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/25/2024] [Accepted: 03/05/2024] [Indexed: 04/04/2024] Open
Abstract
AIM Behavioral psychological symptoms of dementia (BPSD) are sometimes difficult to treat due to severe psychiatric symptoms such as delusions of poisoning and violent behavior. Moreover, in cases of parental neglect, the management of these psychiatric symptoms becomes more difficult. Therefore, home-visiting doctors sometimes have to manage patients with BPSD and severe psychiatric symptoms, and a new approach is needed. In this case report, the effect of blonanserin transdermal patch on these patients is to be highlighted. METHODS The patient is a 91-year-old woman diagnosed with Alzheimer's disease. She had severe BPSD such as delusion of robbery and violent behavior, and refused oral medications including memantine and yokukansan. Then she was treated with blonanserin transdermal patch (20 mg/day). The severity of psychiatric symptoms of BPSD was assessed over time using the Neuropsychiatric Inventory (NPI) score. Moreover, the patient's cognitive function was also assessed over time by Mini-Mental State Examination (MMSE). RESULTS After the introduction of blonanserin patch, the patient's psychiatric symptoms were stabilized markedly, and both NPI and MMSE scores improved. The patient was able to stay at home calmly and was mentally well stabilized to the extent that she did not require hospitalization. No apparent side effects were admitted. CONCLUSIONS The blonanserin transdermal patch may be able to manage BPSD at home and is effective in patients who refuse oral medications. Home-visiting doctors may consider the use of blonanserin patches at home for patients with severe BPSD, manifesting as delusions of poisoning and refusing oral drugs.
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Affiliation(s)
- Junji Yamaguchi
- Asakusa Family ClinicTokyoJapan
- Department of Psycho‐OncologyNational Cancer Center HospitalTokyoJapan
| | - Ryoichi Sadahiro
- Department of Psycho‐OncologyNational Cancer Center HospitalTokyoJapan
| | - Takatoshi Hirayama
- Department of Psycho‐OncologyNational Cancer Center HospitalTokyoJapan
- Kokoro Support ClinicTokyoJapan
| | - Saho Wada
- Department of Psycho‐OncologyNational Cancer Center HospitalTokyoJapan
| | - Rika Nakahara
- Department of Psycho‐OncologyNational Cancer Center HospitalTokyoJapan
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Gao T, Deng H, Sheng J, Wu B, Liu Z, Yang F, Wang L, Hu S, Wang X, Li H, Pu C, Yu X. Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial. Front Psychiatry 2024; 15:1345978. [PMID: 38571994 PMCID: PMC10988613 DOI: 10.3389/fpsyt.2024.1345978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 02/27/2024] [Indexed: 04/05/2024] Open
Abstract
OBJECTIVES This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. METHODS In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. RESULTS A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. CONCLUSION Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.
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Affiliation(s)
- Tianqi Gao
- Peking University Sixth Hospital, Peking University Institute of Mental Health, National Health Commission (NHC) Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Hong Deng
- Mental Health Center, West China Hospital of Sichuan University, Chengdu, China
| | - Jianhua Sheng
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin Wu
- Department of Psychiatry, Xi’an Mental Health Center, Xi’an, China
| | - Zhening Liu
- Mental Health Institute of the Second Xiangya Hospital, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, The State Key Laboratory of Medical Genetics, Central South University, Changsha, China
| | - Fude Yang
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
| | - Lina Wang
- Department of Psychiatry, Tianjin Anding Hospital, Tianjin, China
| | - Shaohua Hu
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xijin Wang
- Department of Psychiatry, The First Psychiatric Hospital of Harbin, Harbin, China
| | - Haiyun Li
- Medical Affairs, Sumitomo Pharma (Suzhou) Co., Ltd., Shanghai, China
| | - Chengcheng Pu
- Peking University Sixth Hospital, Peking University Institute of Mental Health, National Health Commission (NHC) Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Xin Yu
- Peking University Sixth Hospital, Peking University Institute of Mental Health, National Health Commission (NHC) Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
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Deng SW, Xu Q, Jiang WL, Hong B, Li BH, Sun DW, Yang HB. Efficacy and safety of blonanserin versus risperidone in the treatment of schizophrenia: a systematic review and meta-analysis of randomized controlled trials. BMC Psychiatry 2023; 23:740. [PMID: 37821875 PMCID: PMC10568781 DOI: 10.1186/s12888-023-05240-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 09/30/2023] [Indexed: 10/13/2023] Open
Abstract
BACKGROUND We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia. METHODS We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence. RESULTS A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P<0.05), but the incidence of extrapyramidal symptoms (EPS) was higher (P<0.05). CONCLUSION The efficacy of blonanserin is similar to that of risperidone, but it is unclear whether blonanserin is more effective than risperidone at improving cognitive and social function. More high-quality studies are needed to verify the efficacy and safety of blonanserin in the future.
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Affiliation(s)
- Shu-Wen Deng
- College of Pharmacy, Qiqihar Medical University, Qiqihar, China
| | - Qian Xu
- The 8th Affiliated Hospital of Qiqihar Medical University, No.192 Rangdu Road, Ranghulu district, Daqing, Heilongjiang, China.
| | - Wen-Long Jiang
- The 8th Affiliated Hospital of Qiqihar Medical University, No.192 Rangdu Road, Ranghulu district, Daqing, Heilongjiang, China
| | - Bo Hong
- College of Pharmacy, Qiqihar Medical University, Qiqihar, China
| | - Bo-Hui Li
- The 8th Affiliated Hospital of Qiqihar Medical University, No.192 Rangdu Road, Ranghulu district, Daqing, Heilongjiang, China
| | - Da-Wei Sun
- The 8th Affiliated Hospital of Qiqihar Medical University, No.192 Rangdu Road, Ranghulu district, Daqing, Heilongjiang, China
| | - Hai-Bo Yang
- The 8th Affiliated Hospital of Qiqihar Medical University, No.192 Rangdu Road, Ranghulu district, Daqing, Heilongjiang, China
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Bo Q, Wang X, Liu X, Sang H, Xun Z, Zhang R, Yang X, Deng H, Li K, Chen J, Sun M, Zhao G, Liu X, Cai D, Zhan G, Li J, Li H, Wang G. Effectiveness and safety of blonanserin in young and middle-aged female patients with schizophrenia: data from a post-marketing surveillance. BMC Psychiatry 2023; 23:115. [PMID: 36810039 PMCID: PMC9945355 DOI: 10.1186/s12888-023-04598-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 02/07/2023] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND A post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance. METHODS A 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18-40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin. RESULTS A total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P < 0.001, compared with baseline). EPS (20.2%) including akathisia, tremor, dystonia, and parkinsonism were found as the most frequent ADRs. The mean weight gain was 0.27 ± 2.5 kg at 12 weeks from the baseline. Four cases (1%) of prolactin elevation were observed during the period of surveillance. CONCLUSION Blonanserin significantly improved the symptoms of schizophrenia in female patients aged 18-40 years; the drug was well tolerated and had a low tendency to cause metabolic side effects, including prolactin elevation in these patients. Blonanserin might be a reasonable drug for the treatment of schizophrenia in young and middle-aged female patients.
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Affiliation(s)
- Qijing Bo
- grid.24696.3f0000 0004 0369 153XThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, 100088 China
| | - Xijin Wang
- Department of Psychiatry, The First Psychiatric Hospital of Harbin, Harbin, Heilongjiang 150010 China
| | - Xuejun Liu
- Department of Psychiatry, Brain Hospital of Hunan Province, Changsha, Hunan 410007 China
| | - Hong Sang
- Mental Health Center, Changchun Sixth Hospital, Changchun, Jilin 130052 China
| | - Zhiyuan Xun
- grid.440287.d0000 0004 1764 5550Department of Psychiatry, Tianjin Anding Hospital, Tianjin, Tianjin, 300222 China
| | - Ruiling Zhang
- Department of Psychiatry, Henan Mental Hospital, Xinxiang, Henan 453002 China
| | - Xiaodong Yang
- grid.452754.5Department of Psychiatry, Shandong Mental Health Center, Jinan, Shandong 250014 China
| | - Huaili Deng
- Department of Psychology, Psychiatric Hospital of Taiyuan City, Taiyuan, Shanxi, 030000 China
| | - Keqing Li
- Department of Psychiatry, Hebei Provincial Mental Health Center, Baoding, Hebei 071000 China
| | - Jindong Chen
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011 China
| | - Meijuan Sun
- Department of Pharmacy, Daqing Third Hospital, Daqing, Heilongjiang 163712 China
| | - Guijun Zhao
- Department of Psychiatry, Guangyuan Mental Health Center, Guangyuan, Sichuan 628001 China
| | - Xianglai Liu
- Institute of Mental Health, Hainan Provincial Anning Hospital, Haikou, Hainan, 570206 China
| | - Duanfang Cai
- Department of Psychiatry, The Fifth People’s Hospital of Zigong, Zigong, Sichuan 643020 China
| | - Guilai Zhan
- Department of Psychiatry, Xuhui Mental Health center, Shanghai, 200232 China
| | - Juhong Li
- grid.517561.1Department of Psychiatry, The Fourth People’s Hospital of Chengdu, Chengdu, Sichuan 610036 China
| | - Haiyun Li
- Medical Affairs, Sumitomo Pharma (Suzhou) Co., Ltd, Shanghai, 200025 China
| | - Gang Wang
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100088, China. .,The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China.
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Pu C, Lei L, Yang F, Deng H, Sheng J, Liu Z, Hu S, Wang L, Wu B, Bo Q, Inoue Y, Yu X. Effectiveness and safety of blonanserin for improving social and cognitive functions in patients with first-episode schizophrenia: a study protocol for a prospective, multicentre, single-arm clinical trial. BMJ Open 2022; 12:e054079. [PMID: 35443947 PMCID: PMC9021809 DOI: 10.1136/bmjopen-2021-054079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 03/27/2022] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION Both the pharmacological characteristics of blonanserin and its related small sample size studies suggest that blonanserin could alleviate social and cognitive dysfunctions in patients with schizophrenia. However, no large sample size studies have been performed so far. This study aimed to investigate the effectiveness and safety of blonanserin in improving social and cognitive functions in patients with first-episode schizophrenia. METHODS AND ANALYSIS This is a prospective, multicentre, single-arm clinical trial. A total of 188 patients with first-episode schizophrenia will be enrolled and will undergo a 0-7 day washout period before blonanserin administration. Doses of blonanserin will first be set to 4 mg P.O. twice per day after meals and gradually increased to 8-16 mg/d P.O., depending on patient's age and symptoms, for 26 weeks. Maximum dose of blonanserin will not be exceeding 24 mg/day. The primary endpoint of the study is the changes of Personal and Social Performance (PSP) score in patients from baseline to week 26. Secondary endpoints include changes in MATRICS consensus cognitive battery (MCCB), Paced Auditory Serial Addition Test (PASAT), grooved pegboard test (GPT), Positive and Negative Syndrome Scale (PANSS) total score and PANSS 5-factor subscale scores. Other endpoints include changes of serum brain-derived neurotrophic factor (BDNF) at corresponding visits and MRI results. Moreover, incidence of adverse events, changes in endocrine and metabolic profiles, renal, hepatic and sexual functions and extrapyramidal symptoms will be strictly monitored and recorded. ETHICS AND DISSEMINATION The study was approved by the ethics committee of the leading site Peking University Sixth Hospital (No. 2018-18), and all included patients are requested to provide written informed consent before enrolment. The study will be conducted according to the principles of the Declaration of Helsinki and follow the principles for clinical research. TRIAL REGISTRATION NUMBER NCT03784222.
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Affiliation(s)
- Chengcheng Pu
- Department of Clinical Research, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Lei Lei
- Medical Department, Sumitomo Pharma (Suzhou) Co, Shanghai, China
| | - Fude Yang
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
| | - Hong Deng
- Mental Health Center, West China Hospital of Sichuan University, Chengdu, China
| | - Jianhua Sheng
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai, China
| | - Zhening Liu
- Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha, China
| | - Shaohua Hu
- Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lina Wang
- Department of Psychiatry and Imaging-Genetics and Co-morbidity (PNGC-Lab), Tianjin Anding Hospital, Tianjin, China
| | - Bin Wu
- Department of Psychiatry, Xi'an Mental Health Center, Xi'an, China
| | - Qijing Bo
- Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China
| | - Yoshifumi Inoue
- Medical Affairs Department, Sumitomo Dainippon Pharma Co, Osaka, Japan
| | - Xin Yu
- Department of Clinical Research, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
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Ohi K, Takai K, Kuramitsu A, Sugiyama S, Shioiri T. Switching from blonanserin oral tablets/powders to transdermal patches alleviates extrapyramidal symptoms in patients with schizophrenia: A 52-week open-label study. Prog Neuropsychopharmacol Biol Psychiatry 2022; 113:110470. [PMID: 34740708 DOI: 10.1016/j.pnpbp.2021.110470] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/18/2021] [Accepted: 10/29/2021] [Indexed: 11/24/2022]
Abstract
Blonanserin is a second-generation antipsychotic for the treatment of schizophrenia. Blonanserin has two different routes of administration: oral tablets/powder and transdermal patches. The aim of this study was to investigate as a post-hoc analysis of an original study whether switching from blonanserin tablets/powders to transdermal patches would reduce extrapyramidal symptoms (EPS) and/or the dose of antiparkinsonian drugs for the stabilization of blood pharmacokinetics in patients with schizophrenia. Patients with schizophrenia (n = 155) were enrolled in either cohort 1 or 2. In cohort 1 (n = 97), patients received 40-80 mg/day blonanserin transdermal patches for one year after taking 8-16 mg/day blonanserin tablets for 6 weeks, and the dose of patches was determined based on the dose of the tablets. In cohort 2 (n = 58), all patients started with 40 mg/day blonanserin patches and then received 40-80 mg/day for a year after taking blonanserin tablets/powders. Changes from the start of transdermal patch treatment in EPS and the dose of antiparkinsonian drugs at 3, 6, and 12 months were assessed using the Drug-Induced EPS Scale (DIEPSS) and biperiden equivalents of total antiparkinsonian drugs (BPD-eq), respectively. Among 155 patients, only four patients in cohort 1 discontinued owing to EPS during a patch period. Significant improvements from the start of patch treatment in the DIEPSS total score at any point were observed (mean change±SD): -0.44 ± 1.50 (p = 0.013), -0.07 ± 1.78 (p = 0.73), and - 0.14 ± 1.37 (p = 0.44) in cohort 1 and - 0.16 ± 1.32 (p = 0.40), -0.74 ± 1.92 (p = 0.020), and - 0.81 ± 2.22 (p = 0.047) in cohort 2 at 3, 6, and 12 months, respectively. In contrast, there were no significant changes from the start of patch treatment in BPD-eq at any month (p > 0.05). Transdermal patches of blonanserin are a more effective route of administration to diminish EPS than oral tablets/powder.
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Affiliation(s)
- Kazutaka Ohi
- Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan; Department of General Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
| | - Kentaro Takai
- Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Ayumi Kuramitsu
- Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Shunsuke Sugiyama
- Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Toshiki Shioiri
- Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
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Saito T, Sugimoto S, Sakaguchi R, Nakamura H, Ishigooka J. Efficacy and Safety of Blonanserin Oral Tablet in Adolescents with Schizophrenia: A 6-Week, Randomized Placebo-Controlled Study. J Child Adolesc Psychopharmacol 2022; 32:12-23. [PMID: 35133884 PMCID: PMC8884167 DOI: 10.1089/cap.2021.0013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Objectives: To evaluate the short-term efficacy and safety of blonanserin in adolescents with schizophrenia. Methods: This 6-week multicenter, double-blind, randomized, placebo-controlled study investigated fixed-dose blonanserin (8 or 16 mg/day) in patients 12-18 years of age diagnosed with schizophrenia, as indicated by a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 and a Clinical Global Impressions-Severity score of ≥3. The primary endpoint was change from baseline to week 6 in the PANSS total score, using a mixed model for repeated measures analysis. Safety was assessed by the incidence and severity of adverse events (AEs). Results: Among 151 randomized patients, 150 were included in the primary analysis population. Demographic and clinical characteristics were similar across groups at baseline. The rate of study discontinuation was 14.9%, 23.5%, and 28.3% in patients administered with placebo, blonanserin 8 mg/day, and blonanserin 16 mg/day, respectively. The least-squares mean change (95% confidence interval [CI]) from baseline to week 6 in PANSS total score was -10.6 (-16.10 to -5.10), -15.3 (-20.80 to -9.86), and -20.5 (-25.89 to -15.16) in patients administered placebo, 8 mg/day blonanserin, and 16 mg/day blonanserin, respectively. The 16-mg/day blonanserin group showed significantly greater reduction in the PANSS total score than the placebo group (least-squares mean difference [95% CI]: -9.9 [-17.61 to -2.25], p = 0.012, effect size: 0.538), although the 8-mg/day group showed no significant difference. The incidence of AEs such as akathisia, somnolence, and hyperprolactinemia was higher in the blonanserin groups than in the placebo group. AEs associated with blonanserin were generally mild and were consistent with its known profile in adults with schizophrenia. Conclusions: Blonanserin achieved a sufficient efficacy in adolescent patients, and the safety profile was similar to that in adults, which suggests that blonanserin may be a safe treatment option for adolescents with schizophrenia. Study registration number: Japic CTI-111724.
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Affiliation(s)
- Takuya Saito
- Department of Child and Adolescent Psychiatry, Hokkaido University Hospital, Sapporo, Japan
| | - Saori Sugimoto
- Sumitomo Dainippon Pharma Co., Ltd., Chuo-ku, Tokyo, Japan
| | | | - Hiroshi Nakamura
- Sumitomo Dainippon Pharma Co., Ltd., Chuo-ku, Tokyo, Japan.,Address correspondence to: Hiroshi Nakamura, MS, Sumitomo Dainippon Pharma Co., Ltd., 1-13-1 Kyobashi, Chuo-Ku, Tokyo 104-8356, Japan
| | - Jun Ishigooka
- Institute of CNS Pharmacology, Shibuya-ku, Tokyo, Japan
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Torrisi SA, Geraci F, Contarini G, Salomone S, Drago F, Leggio GM. Dopamine D3 Receptor, Cognition and Cognitive Dysfunctions in Neuropsychiatric Disorders: From the Bench to the Bedside. Curr Top Behav Neurosci 2022; 60:133-156. [PMID: 35435642 DOI: 10.1007/7854_2022_326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The dopamine D3 receptor (D3R) plays a prominent role in the modulation of cognition in healthy individuals, as well as in the pathophysiological mechanism underlying the cognitive deficits affecting patients suffering from neuropsychiatric disorders. At a therapeutic level, a growing body of evidence suggests that the D3R blockade enhances cognitive and thus it may be an optimal therapeutic strategy against cognitive dysfunctions. However, this is not always the case because other ligands targeting the D3R, and behaving as partial agonists or biased agonists, may exert their pro-cognitive effect by maintaining adequate level of dopamine in key brain areas tuning cognitive performances. In this chapter, we review and discuss preclinical and clinical findings with the aim to remark the crucial role of the D3R in cognition and to strengthen the message that drugs targeting D3R may be excellent cognitive enhancers for the treatment of several neuropsychiatric and neurological disorders.
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Affiliation(s)
| | - Federica Geraci
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Gabriella Contarini
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Salomone Salomone
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Gian Marco Leggio
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
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Hori H, Yasui-Furukori N, Hasegawa N, Iga JI, Ochi S, Ichihashi K, Furihata R, Kyo Y, Takaesu Y, Tsuboi T, Kodaka F, Onitsuka T, Okada T, Murata A, Kashiwagi H, Iida H, Hashimoto N, Ohi K, Yamada H, Ogasawara K, Yasuda Y, Muraoka H, Usami M, Numata S, Takeshima M, Yamagata H, Nagasawa T, Tagata H, Makinodan M, Kido M, Katsumoto E, Komatsu H, Matsumoto J, Kubota C, Miura K, Hishimoto A, Watanabe K, Inada K, Kawasaki H, Hashimoto R. Prescription of Anticholinergic Drugs in Patients With Schizophrenia: Analysis of Antipsychotic Prescription Patterns and Hospital Characteristics. Front Psychiatry 2022; 13:823826. [PMID: 35656353 PMCID: PMC9152135 DOI: 10.3389/fpsyt.2022.823826] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 04/04/2022] [Indexed: 11/13/2022] Open
Abstract
In several clinical guidelines for schizophrenia, long-term use of anticholinergic drugs is not recommended. We investigated the characteristics of the use of anticholinergics in patients with schizophrenia by considering psychotropic prescription patterns and differences among hospitals. A cross-sectional, retrospective prescription survey at the time of discharge was conducted on 2027 patients with schizophrenia from 69 Japanese hospitals. We examined the relations among psychotropic drug prescriptions regarding anticholinergic prescription. We divided the hospitals into three groups-low rate group (LG), medium rate group (MG), and high rate group (HG)-according to their anticholinergic prescription rates, and analyzed the relationship between anticholinergic prescription rates and antipsychotic prescription. Anticholinergic drugs were prescribed to 618 patients (30.5%), and the prescription rates were significantly higher for high antipsychotic doses, antipsychotic polypharmacy, and first-generation antipsychotics (FGAs) use. The anticholinergic prescription rate varied considerably among hospitals, ranging from 0 to 66.7%, and it was significantly higher in patients with antipsychotic monotherapy, antipsychotic polypharmacy, and normal and high doses of antipsychotics in HG than in those LG and MG. The anticholinergics prescription rate in patients with second-generation antipsychotic monotherapy in HG was also significantly higher than in those LG and MG; however, the difference was no longer significant in patients with FGA monotherapy. Conclusively, in addition to high antipsychotic doses, antipsychotic polypharmacy, and FGA use, hospital characteristics influence the prescribing of anticholinergic drugs.
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Affiliation(s)
- Hikaru Hori
- Department of Psychiatry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Norio Yasui-Furukori
- Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi, Japan
| | - Naomi Hasegawa
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Jun-Ichi Iga
- Department of Neuropsychiatry Molecules and Function, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Shinichiro Ochi
- Department of Neuropsychiatry Molecules and Function, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Kayo Ichihashi
- Department of Neuropsychiatry, University of Tokyo Hospital, Tokyo, Japan
| | - Ryuji Furihata
- Agency for Student Support and Disability Resources, Kyoto University, Kyoto, Japan
| | - Yoshitaka Kyo
- Department of Psychiatry, School of Medicine, Kitasato University, Tokyo, Japan
| | - Yoshikazu Takaesu
- Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
| | - Takashi Tsuboi
- Department of Neuropsychiatry, Kyorin University School of Medicine, Mitaka, Japan
| | - Fumitoshi Kodaka
- Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan
| | - Toshiaki Onitsuka
- Department of Neuroimaging Psychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tsuyoshi Okada
- Department of Psychiatry, Jichi Medical University, Tochigi, Japan
| | - Atsunobu Murata
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Hiroko Kashiwagi
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.,Department of Psychiatry, National Center of Neurology and Psychiatry Hospital, Kodaira, Japan
| | - Hitoshi Iida
- Department of Psychiatry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Naoki Hashimoto
- Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Kazutaka Ohi
- Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hisashi Yamada
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.,Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kazuyoshi Ogasawara
- Center for Postgraduate Clinical Training and Career Development, Nagoya University Hospital, Nagoya, Japan
| | - Yuka Yasuda
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.,Life Grow Brilliant Mental Clinic, Medical Corporation Foster, Osaka, Japan
| | - Hiroyuki Muraoka
- Department of Psychiatry, Tokyo Women's Medical University, Tokyo, Japan
| | - Masahide Usami
- Department of Child and Adolescent Psychiatry, Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Shusuke Numata
- Department of Psychiatry, Graduate School of Biomedical Science, Tokushima University, Tokushima, Japan
| | - Masahiro Takeshima
- Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan
| | - Hirotaka Yamagata
- Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University School of Medicine, Yamaguchi, Japan
| | - Tatsuya Nagasawa
- Department of Neuropsychiatry, Kanazawa Medical University, Uchinada, Japan
| | - Hiromi Tagata
- Department of Neuropsychiatry, Toho University Graduate School of Medicine, Tokyo, Japan
| | - Manabu Makinodan
- Department of Psychiatry, Nara Medical University School of Medicine, Kashihara, Japan
| | - Mikio Kido
- Toyama City Hospital, Toyama, Japan.,Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | | | - Hiroshi Komatsu
- Department of Psychiatry, Tohoku University Hospital, Sendai, Japan
| | - Junya Matsumoto
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Chika Kubota
- Department of Psychiatry, National Center of Neurology and Psychiatry Hospital, Kodaira, Japan
| | - Kenichiro Miura
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Akitoyo Hishimoto
- Department of Psychiatry, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Koichiro Watanabe
- Department of Neuropsychiatry, Kyorin University School of Medicine, Mitaka, Japan
| | - Ken Inada
- Department of Psychiatry, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroaki Kawasaki
- Department of Psychiatry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Ryota Hashimoto
- National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan
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10
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Murasaki M, Inoue Y, Nakamura H, Kinoshita T. Long-term oral blonanserin treatment for schizophrenia: a review of Japanese long-term studies. Ann Gen Psychiatry 2021; 20:41. [PMID: 34493318 PMCID: PMC8425119 DOI: 10.1186/s12991-021-00361-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 08/08/2021] [Indexed: 11/22/2022] Open
Abstract
In general, the course of schizophrenia is chronic accompanied not only by positive and negative symptoms but also by cognitive dysfunction associated with psychosocial disability, and thus treatment combining antipsychotics and psychological therapy is considered promising. This review focused on two prospective, open-label, multicenter, phase 3 long-term studies for approval of oral blonanserin for the treatment of schizophrenia. These two studies included both inpatients and outpatients with variable disease duration or symptom prominence according to the Positive and Negative Syndrome Scale (PANSS). The selected two studies consisted of almost the same study schedule and eligibility criteria but different protocols regarding prior medications and concomitant antipsychotics. The proportion of patients who had a baseline PANSS negative score higher than the positive score was 82.2 and 67.2% in the two studies. In both studies, patients with an illness duration of ≥ 10 years were the most common. Based on the clinical symptoms at baseline, the physician determined the treatment: blonanserin monotherapy, blonanserin in combination with the existing antipsychotic medication, or therapy simplified to haloperidol together with blonanserin. The 28-week completion rate for long-term blonanserin treatment was high in both studies (82.2 and 78.7%). The types of adverse events in both studies were similar to those in the preceding 8-week randomized, active-controlled studies in Japan, which were included in the application package for the approval of oral blonanserin for patients with schizophrenia. Long-term blonanserin use did not increase the risk of extrapyramidal symptoms but reduced the dose of antiparkinsonian drugs, minimally affecting functioning. In both studies, the PANSS total score, positive score, and negative score were improved at the last observation carried forward compared with those at baseline. In conclusion, blonanserin is useful for long-term treatment of chronic schizophrenic patients when the appropriate management of clinical symptoms and adverse drug reactions are applied. Blonanserin might represent a promising treatment option that partially or completely relieves patients with chronic schizophrenia of polypharmacy. Blonanserin may possibly fit both the current real-world clinical setting and the currently recommended approach to antipsychotic medication.
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Affiliation(s)
| | - Yoshifumi Inoue
- Medical Affairs, Sumitomo Dainippon Pharma Co, Ltd, 1-13-1 Kyobashi, Chuo, Tokyo, 104-8356, Japan
| | - Hiroshi Nakamura
- Medical Affairs, Sumitomo Dainippon Pharma Co, Ltd, 1-13-1 Kyobashi, Chuo, Tokyo, 104-8356, Japan.
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11
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Sakai S, Morimoto Y, Matsuzaka Y, Nakano T, Kanegae S, Imamura A, Ozawa H. Switching from blonanserin tablets to blonanserin transdermal patches improves tardive dyskinesia: A case report. Neuropsychopharmacol Rep 2021; 41:440-443. [PMID: 34357702 PMCID: PMC8411311 DOI: 10.1002/npr2.12200] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 07/05/2021] [Accepted: 07/15/2021] [Indexed: 12/27/2022] Open
Abstract
Tardive dyskinesia (TD) is a common side effect of antipsychotics, and it remains a persistent and challenging problem. The blonanserin transdermal patch, developed in Japan and launched in September 2019, is the first antipsychotic transdermal treatment. Here, we describe a patient with schizophrenia who exhibited markedly improved orofacial dyskinesia after switching from blonanserin tablets to blonanserin transdermal patches. We speculate that the patch formulation might have led to more stable plasma blonanserin levels, thus reducing the side effects. Specifically, the patch formulation might have contributed to stable plasma levels via the continuous and direct absorption of blonanserin through the skin. The present case report shows that switching from blonanserin tablets to blonanserin patches may reduce EPSs while maintaining a good therapeutic effect.![]()
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Affiliation(s)
- Shintaro Sakai
- Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
| | - Yoshiro Morimoto
- Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
| | - Yusuke Matsuzaka
- Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
| | - Takeshi Nakano
- Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
| | - Shinji Kanegae
- Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
| | - Akira Imamura
- Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
| | - Hiroki Ozawa
- Department of Neuropsychiatry, Unit of Translation Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Child and Adolescent Psychiatry Community Partnership Unit, Nagasaki University Hospital, Nagasaki, Japan
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12
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Shiina A, Hasegawa T, Iyo M. Possible effect of blonanserin on gambling disorder: A clinical study protocol and a case report. World J Clin Cases 2021; 9:2469-2477. [PMID: 33889612 PMCID: PMC8040182 DOI: 10.12998/wjcc.v9.i11.2469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/08/2021] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gambling disorder is characterized by excessive and recurrent gambling and can have serious negative social consequences. Although several psychotherapeutic and pharmacological approaches have been used to treat gambling disorder, new treatment strategies are needed. Growing evidence suggests that dopamine D3 receptor plays a specific role in the brain reward system. AIM To investigate if blonanserin, a dopamine D3 receptor antagonist, would be effective in reducing gambling impulses in patients with gambling disorder. METHODS We developed a study protocol to measure the efficacy and safety of blonanserin as a potential drug for gambling disorder, in which up to 12 mg/d of blonanserin was prescribed for 8 wk. RESULTS A 37-year-old female patient with gambling disorder, intellectual disability, and other physical diseases participated in the pilot study. The case showed improvement of gambling symptoms without any psychotherapy. However, blonanserin was discontinued owing to excessive saliva production. CONCLUSION This case suggests that blonanserin is potentially an effective treatment for patients with gambling disorder who resist standard therapies, but it also carries a risk of adverse effects. Further studies are needed to confirm the findings.
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Affiliation(s)
- Akihiro Shiina
- Division of Medical Treatment and Rehabilitation, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan
| | - Tadashi Hasegawa
- Department of Psychiatry, Chiba University Hospital, Chiba 260-8670, Japan
| | - Masaomi Iyo
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
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13
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Inoue Y, Tsuchimori K, Nakamura H. Safety and effectiveness of oral blonanserin for schizophrenia: A review of Japanese post-marketing surveillances. J Pharmacol Sci 2020; 145:42-51. [PMID: 33357778 DOI: 10.1016/j.jphs.2020.09.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 09/17/2020] [Accepted: 09/23/2020] [Indexed: 01/22/2023] Open
Abstract
Schizophrenia significantly limits social functioning with positive and negative symptoms and cognitive dysfunction. Blonanserin (LONASEN®), a novel second-generation antipsychotic approved for treating schizophrenia in Japan in 2008, reportedly shows beneficial effects on cognitive function as well as positive and negative symptoms, with potential for improving social functioning. To understand the safety and effectiveness of blonanserin in the real clinical practice, five Japanese post-marketing surveillances have been conducted and published to date. In this article, we reviewed all the Japanese post-marketing surveillances and discussed the clinical usefulness of blonanserin in patients with schizophrenia having diverse clinical characteristics. Adverse drug reactions, such as akathisia and extrapyramidal symptoms, were common in all surveillances. However, those specific to second-generation antipsychotics, such as weight gain and abnormalities in glycometabolism or lipid metabolism, were rarely observed. In addition, no adverse drug reactions apart from clinical trial results were found. Brief Psychiatric Rating Scale total scores in all surveillances significantly lowered at the last evaluation than at baseline. These results were consistent through 1-year of treatment, suggesting that effectiveness is maintained even after long-term use. In conclusion, blonanserin is considered a beneficial drug in real clinical practice for patients with schizophrenia having diverse characteristics.
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Affiliation(s)
- Yoshifumi Inoue
- Medical Affairs, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan.
| | - Kimiko Tsuchimori
- Corporate Governance Material Review Group, Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan.
| | - Hiroshi Nakamura
- Medical Affairs, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan.
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14
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Iwata N, Ishigooka J, Kim WH, Yoon BH, Lin SK, Sulaiman AH, Cosca R, Wang L, Suchkov Y, Agarkov A, Watabe K, Matsui T, Sato T, Inoue Y, Higuchi T, Correll CU, Kane JM. Efficacy and safety of blonanserin transdermal patch in patients with schizophrenia: A 6-week randomized, double-blind, placebo-controlled, multicenter study. Schizophr Res 2020; 215:408-415. [PMID: 31471246 DOI: 10.1016/j.schres.2019.07.055] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 07/26/2019] [Accepted: 07/29/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia. METHODS This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p < 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia. CONCLUSIONS Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability.
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Affiliation(s)
- Nakao Iwata
- Department of Psychiatry, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake-shi, Aichi 470-1192, Japan.
| | - Jun Ishigooka
- Institute of CNS Pharmacology, 4-26-11, Sendagaya, Shibuya-Ku, Tokyo 151-0051, Japan.
| | - Won-Hyoung Kim
- Department of Psychiatry, Inha University Hospital, 27, Inhang-ro, Jung-gu Incheon, 22332, Republic of Korea
| | - Bo-Hyun Yoon
- Department of Psychiatry, Naju National Hospital, 1328-31 Senam-ro, Sanpo-myeon, Naju-City, Jeonnam 58213, Republic of Korea.
| | - Shih-Ku Lin
- Department of Psychiatry, Taipei City Hospital and Psychiatric Center, No.309, Songde Rd., Xinyi Dist., Taipei City 110, Taiwan, ROC.
| | - Ahmad Hatim Sulaiman
- Department of Psychological Medicine, University Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia.
| | - Rowena Cosca
- Department of Psychiatry, Western Visayas Medical Center, Q. Abeto St., Mandurriao, Iloilo City 5000, Philippines
| | - Lina Wang
- Department of Mood Disorders, Tianjin Anding Hospital, Liulin Road 13, Hexi District, Tianjin 300222, China
| | - Yury Suchkov
- Departments of Psychiatric Hospital, SBHI of Nizhny Novgorod Region "Clinical Psychiatric Hospital No. 1 of Nizhny Novgorod", 41 Ulianova St., Nizhny Novgorod 603155, Russia
| | - Alexey Agarkov
- Research Center of Mental Health, Tomsk National Research Medical Center, Russian Academy of Sciences, 4 Aleutskaya St., Tomsk 634014, Russia
| | - Kei Watabe
- Sumitomo Dainippon Pharma Co., Ltd., 13-1, Kyobashi 1-Chome, Chuo-ku, Tokyo 104-8356, Japan
| | - Tomohito Matsui
- Sumitomo Dainippon Pharma Co., Ltd., 13-1, Kyobashi 1-Chome, Chuo-ku, Tokyo 104-8356, Japan
| | - Takayuki Sato
- Sumitomo Dainippon Pharma Co., Ltd., 13-1, Kyobashi 1-Chome, Chuo-ku, Tokyo 104-8356, Japan
| | - Yoshifumi Inoue
- Sumitomo Dainippon Pharma Co., Ltd., 13-1, Kyobashi 1-Chome, Chuo-ku, Tokyo 104-8356, Japan.
| | - Teruhiko Higuchi
- Japan Depression Center, 1-7, Rokubancho, Chiyoda-ku, Tokyo 102-0085, Japan
| | - Christoph U Correll
- Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 75-59 263rd Street Glen Oaks, New York 11004, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA; Department of Psychiatry, The Zucker Hillside Hospital, 75-59 263rd Street Glen Oaks, New York 11004, USA; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
| | - John M Kane
- Department of Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 75-59 263rd Street Glen Oaks, New York 11004, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA; Department of Psychiatry, The Zucker Hillside Hospital, 75-59 263rd Street Glen Oaks, New York 11004, USA
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15
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Harvey PD, Nakamura H, Murasaki M. Blonanserin versus haloperidol in Japanese patients with schizophrenia: A phase 3, 8-week, double-blind, multicenter, randomized controlled study. Neuropsychopharmacol Rep 2019; 39:173-182. [PMID: 31041855 PMCID: PMC7292269 DOI: 10.1002/npr2.12057] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/24/2019] [Accepted: 04/02/2019] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE This Japanese, multicenter, randomized, double-blind trial, evaluating the efficacy and safety of blonanserin compared with haloperidol in patients with schizophrenia, was previously published by Murasaki in the Japanese language. In this article, we present the results of the trial based on full analysis dataset instead of per protocol dataset formerly reported and discuss the findings in light of the latest knowledge of pharmacological treatment for schizophrenia. METHODS A total of 265 patients were randomized to receive blonanserin (8 to 24 mg/d) or haloperidol (4 to 12 mg/d) twice daily for 8 weeks. Efficacy assessments included the Clinical Global Impressions-Improvement (CGI-I) and the Positive and Negative Syndrome Scale (PANSS). RESULTS Blonanserin was not inferior to haloperidol with a margin of 10% with respect to the improvement rate on CGI-I at end of study (60.5% vs 50.0%, P < 0.001). The decrease in the PANSS total score did not differ between the drugs (-10.3 vs -7.1). For the PANSS negative symptom score, the decrease was significantly greater with blonanserin than with haloperidol (P = 0.006). Blonanserin was well tolerated. The incidence of adverse events was similar for the two drugs. Extrapyramidal adverse events, sedation, hypotension, and prolactin increase were rarer with blonanserin than with haloperidol. No clinically important weight gain was observed. CONCLUSIONS Blonanserin is as effective as haloperidol for the treatment of schizophrenia. Blonanserin is more effective for negative symptoms with a lower risk of extrapyramidal symptoms compared with haloperidol.
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Affiliation(s)
- Philip D. Harvey
- Leonard M. Miller Professor of Psychiatry and Behavioral SciencesUniversity of Miami Miller School of MedicineMiamiFlorida
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16
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Takeuchi S, Hida H, Uchida M, Naruse R, Yoshimi A, Kitagaki S, Ozaki N, Noda Y. Blonanserin ameliorates social deficit through dopamine-D 3 receptor antagonism in mice administered phencyclidine as an animal model of schizophrenia. Neurochem Int 2019; 128:127-134. [PMID: 30998952 DOI: 10.1016/j.neuint.2019.04.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/02/2019] [Accepted: 04/15/2019] [Indexed: 01/02/2023]
Abstract
Blonanserin differs from other antipsychotic drugs, such as risperidone and olanzapine, and exhibits a higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effect of blonanserin on the social deficit observed in an animal model of schizophrenia and sought to elucidate the molecular mechanism underlying its action. Mice received phencyclidine (PCP: 10 mg/kg/day, s.c.), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, once a day for 14 consecutive days. We then evaluated the sociability, using a social interaction test, and the expression of GluN1 subunit, an essential subunit of the NMDA receptors, in these mice. Blonanserin significantly ameliorated the PCP-induced social deficit, whereas olanzapine and haloperidol did not. This effect of blonanserin was antagonized by 7-OH-DPAT, a dopamine-D3 receptor agonist, and SCH23390, a dopamine-D1 receptor antagonist. However, the ameliorating effect of blonanserin was not inhibited by DOI, a serotonin 5-HT2A receptor agonist. The PCP-induced social deficit was also ameliorated by U99194, a dopamine-D3 receptor antagonist and SKF38393, a dopamine-D1 receptor agonist, being effects antagonized by 7-OH-DPAT or SCH23390. Blonanserin significantly inhibited the decrease in the phosphorylation levels of GluN1 at Ser897 by protein kinase A (PKA) in the prefrontal cortex (PFC) in PCPadministered mice. These results suggest that activation of NMDA receptors due to Ser897-phosphorylation of GluN1 subunit, which is a step linked to dopamine-D1 receptor-PKA signaling through dopamine-D3 receptor antagonism in the PFC, is required for the ameliorating effect of blonanserin on the PCP-induced social deficit. These findings also provide in vivo evidence that blonanserin antagonism of the dopamine-D3 receptors may be useful as a novel treatment strategy and that the dopamine-D3 receptors can be a novel therapeutic target molecule for the social deficit observed in schizophrenia.
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Affiliation(s)
- Saori Takeuchi
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan
| | - Hirotake Hida
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan
| | - Mizuki Uchida
- Division of Clinical Sciences and Neuropsychopharmacology, Graduate School of Pharmacy, Meijo University, Nagoya, 468-8503, Japan
| | - Ryo Naruse
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan
| | - Akira Yoshimi
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan
| | - Shinji Kitagaki
- Department of Medical Chemistry, Graduate School of Pharmacy, Meijo University, Nagoya, 468-8503, Japan
| | - Norio Ozaki
- Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, 466-8560, Japan
| | - Yukihiro Noda
- Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503, Japan; Division of Clinical Sciences and Neuropsychopharmacology, Graduate School of Pharmacy, Meijo University, Nagoya, 468-8503, Japan; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, 466-8560, Japan.
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17
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Tateno A, Sakayori T, Kim WC, Honjo K, Nakayama H, Arakawa R, Okubo Y. Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-PHNO. Int J Neuropsychopharmacol 2018; 21:522-527. [PMID: 29346639 PMCID: PMC6007421 DOI: 10.1093/ijnp/pyy004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 01/10/2018] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. METHODS Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. RESULTS Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%-84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%-88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%-87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%-88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). CONCLUSIONS A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.
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Affiliation(s)
- Amane Tateno
- Department of Neuropsychiatry, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
| | - Takeshi Sakayori
- Department of Neuropsychiatry, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
| | - Woo-chan Kim
- Department of Neuropsychiatry, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
| | - Kazuyoshi Honjo
- Clinical Imaging Center for Healthcare, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
| | - Haruo Nakayama
- Healthcare Solutions Division, Advanced Medical Services Department, Healthcare Business Unit, Hitachi, Ltd., Taito-ku, Tokyo, Japan
| | - Ryosuke Arakawa
- Department of Neuropsychiatry, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
| | - Yoshiro Okubo
- Department of Neuropsychiatry, Nippon Medical School, Bunkyo-ku, Tokyo, Japan,Correspondence: Yoshiro Okubo, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113–8602, Japan ()
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18
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Torrisi SA, Salomone S, Geraci F, Caraci F, Bucolo C, Drago F, Leggio GM. Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through Dopamine D 3 Receptor Blockade. Front Pharmacol 2017; 8:710. [PMID: 29046641 PMCID: PMC5632784 DOI: 10.3389/fphar.2017.00710] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 09/21/2017] [Indexed: 12/30/2022] Open
Abstract
Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity. Multiple lines of evidence point to D3R as a valid therapeutic target for the treatment of several neuropsychiatric disorders including schizophrenia. In the present study, we tested the hypothesis that buspirone, behaving as dopamine D3R antagonist, may have antipsychotic-like activity. Materials and Methods: Effects of acute administration of buspirone was assessed on a wide-range of schizophrenia-relevant abnormalities induced by a single administration of the non-competitive NMDAR antagonist MK-801, in both wild-type mice (WT) and D3R-null mutant mice (D3R-/-). Results: Buspirone (3 mg⋅kg-1, i.p.) was devoid of cataleptogenic activity in itself, but resulted effective in counteracting disruption of prepulse inhibition (PPI), hyperlocomotion and deficit of temporal order recognition memory (TOR) induced by MK-801 (0.1 mg⋅kg-1, i.p.) in WT mice. Conversely, in D3R-/- mice, buspirone was ineffective in preventing MK-801-induced TOR deficit and it was only partially effective in blocking MK-801-stimulated hyperlocomotion. Conclusion: Taken together, these results indicate, for the first time, that buspirone, might be a potential therapeutic medication for the treatment of schizophrenia. In particular, buspirone, through its D3R antagonist activity, may be a useful tool for improving the treatment of cognitive deficits in schizophrenia that still represents an unmet need of this disease.
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Affiliation(s)
- Sebastiano Alfio Torrisi
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
| | - Salvatore Salomone
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
| | - Federica Geraci
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
| | - Filippo Caraci
- Department of Drug Sciences, University of Catania, Catania, Italy.,Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy
| | - Claudio Bucolo
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
| | - Gian Marco Leggio
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
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19
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Cui Y, Prabhu VV, Nguyen TB, Devi SM, Chung YC. Longer Telomere Length of T lymphocytes in Patients with Early and Chronic Psychosis. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE 2017; 15:146-152. [PMID: 28449562 PMCID: PMC5426489 DOI: 10.9758/cpn.2017.15.2.146] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 11/30/2016] [Accepted: 12/01/2016] [Indexed: 12/20/2022]
Abstract
Objective To investigate pathological conditions that act as sources of pro-inflammatory cytokines and cytotoxic substances to examine telomere length (TL) in patients with either early (duration of illness [DI] ≤5 years) or chronic (DI >5 years) psychosis using T lymphocytes. Methods Based on these factors and the important role that T lymphocytes play in inflammation, the present study measured the TL of T lymphocytes in patients with either early or chronic psychosis. Additionally, smoking, metabolic syndrome, depression, and cognitive functioning were assessed to control for confounding effects. Results TL was significantly longer in patients with early and chronic psychosis than in healthy control subjects and, moreover, the significance of these findings remained after controlling for age, smoking, metabolic syndrome, DI, chlorpromazine-equivalent dose, and cognitive functioning (F=9.57, degree of freedom=2, p<0.001). Additionally, the DI, chlorpromazine-equivalent doses, and the five-factor scores of the Positive and Negative Syndrome Scale were not significantly correlated with the TL of T lymphocytes in either all patients or each psychosis group. Conclusion Possible mechanisms underlying the effects of antipsychotic medications on telomerase are discussed in the present study, but further studies measuring both telomerase activity and TL using a prospective design will be required.
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Affiliation(s)
- Yin Cui
- Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Vishwanath Vasudev Prabhu
- Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Thong Ba Nguyen
- Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Subramaniam Mohana Devi
- Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Young-Chul Chung
- Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
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20
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Abstract
Although there has been more than 50 years of development, there remains a great need for better antipsychotic medications. This article looks at the recent advances in treatment of schizophrenia. New hypotheses have been suggested that may replace or complement the dopamine hypotheses. The article explores the different novel drugs that impact some of the key neurotransmitter systems currently. Phosphodiesterase 10A inhibitors and α-7 neuronal nicotinic acetylcholine receptor modulators constitute the majority. The marketing of these medications eventually may result in change about how schizophrenia is treated.
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21
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Kotani M, Enomoto T, Murai T, Nakako T, Iwamura Y, Kiyoshi A, Matsumoto K, Matsumoto A, Ikejiri M, Nakayama T, Ogi Y, Ikeda K. The atypical antipsychotic blonanserin reverses (+)-PD-128907- and ketamine-induced deficit in executive function in common marmosets. Behav Brain Res 2016; 305:212-7. [PMID: 26970575 DOI: 10.1016/j.bbr.2016.02.031] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 02/23/2016] [Accepted: 02/26/2016] [Indexed: 10/22/2022]
Abstract
Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia.
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Affiliation(s)
- Manato Kotani
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Takeshi Enomoto
- Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Takeshi Murai
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Tomokazu Nakako
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Yoshihiro Iwamura
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Akihiko Kiyoshi
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Kenji Matsumoto
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Atsushi Matsumoto
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Masaru Ikejiri
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Tatsuo Nakayama
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Yuji Ogi
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan
| | - Kazuhito Ikeda
- Ikeda Lab, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, 564-0053, Japan.
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22
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Blonanserin Augmentation for Treatment-Resistant Somatic Symptom Disorder: A Case Series. Clin Neuropharmacol 2016; 39:112-4. [PMID: 26818044 DOI: 10.1097/wnf.0000000000000134] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The augmentation of selective serotonin reuptake inhibitors with antipsychotics that have a high dopamine-receptor-D2 affinity may be effective in treatment-resistant obsessive-compulsive disorder and somatic symptom disorder, which is similar to illness anxiety disorder. Blonanserin, a novel antipsychotic developed in Japan, has a high affinity for the D2 receptor and weak or very little affinity for other receptors. This article presents two case studies that demonstrate the efficacy of blonanserin augmentation for treatment-resistant somatic symptom disorder. Two patients with treatment-resistant somatic symptom disorder were prescribed concomitant use of blonanserin. Augmentation with blonanserin resulted in the remarkable amelioration of all symptoms. Sedative adverse drug reactions produced by aripiprazole were improved after replacing it with blonanserin. Blonanserin is effective in treatment-resistant somatic symptom disorder. Furthermore, compared with aripiprazole, blonanserin is more likely to result in medication adherence in patients with somatic symptom disorder because it reduced adverse drug reactions.
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23
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Kishi T, Matsuda Y, Matsunaga S, Mukai T, Moriwaki M, Tabuse H, Fujita K, Iwata N. A randomized trial of aripiprazole vs blonanserin for the treatment of acute schizophrenia and related disorders. Neuropsychiatr Dis Treat 2016; 12:3041-3049. [PMID: 27932884 PMCID: PMC5135406 DOI: 10.2147/ndt.s121588] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE There has been no direct comparison of aripiprazole and blonanserin for schizophrenia treatment. We conducted a 24-week, rater-masked, randomized trial of aripiprazole (6-30 mg/d) vs blonanserin (4-24 mg/d) in schizophrenia patients who were not taking any antipsychotic medication for more than 2 weeks before enrollment (UMIN000011194). METHODS The primary outcome measure for efficacy was improvement of Positive and Negative Syndrome Scale (PANSS) total score at week 24. Secondary outcomes were PANSS subscale scores, 21-item Hamilton Rating Scale for Depression (HAMD-21) score, response rate, discontinuation rate, and individual adverse events. RESULTS Forty-four patients were recruited. The discontinuation rate was 86.4% in the aripiprazole group and 68.2% in the blonanserin treatment group. There was no significant difference in mean time to discontinuation between the groups. Although both treatment groups showed significant reductions in the PANSS total score, PANSS subscale scores, and HAMD-21 scores at week 24, the magnitudes of the changes did not differ between the groups. There were no significant differences in the incidences of adverse events including somnolence, extrapyramidal symptoms, prolactin-related adverse events, and weight change between the groups. CONCLUSION Our results suggest similar efficacy and safety profiles of aripiprazole and blonanserin in the patients with schizophrenia. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole and blonanserin in schizophrenia.
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Affiliation(s)
- Taro Kishi
- Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi
| | - Yuki Matsuda
- Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi
| | - Shinji Matsunaga
- Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi
| | - Tomohiko Mukai
- Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi; Department of Psychiatry, Okehazama Hospital, Toyoake, Aichi
| | - Masatsugu Moriwaki
- Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi; Department of Psychiatry, Okehazama Hospital, Toyoake, Aichi
| | - Hideaki Tabuse
- Department of Psychiatry, Holy Cross Hospital, Toki, Gifu, Japan
| | - Kiyoshi Fujita
- Department of Psychiatry, Okehazama Hospital, Toyoake, Aichi
| | - Nakao Iwata
- Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi
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24
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Tatara A, Shimizu S, Masui A, Tamura M, Minamimoto S, Mizuguchi Y, Ochiai M, Mizobe Y, Ohno Y. Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin. Pharmacol Biochem Behav 2015; 138:14-9. [DOI: 10.1016/j.pbb.2015.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Revised: 08/22/2015] [Accepted: 09/02/2015] [Indexed: 11/30/2022]
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25
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Huang M, Kwon S, Oyamada Y, Rajagopal L, Miyauchi M, Meltzer HY. Dopamine D3 receptor antagonism contributes to blonanserin-induced cortical dopamine and acetylcholine efflux and cognitive improvement. Pharmacol Biochem Behav 2015; 138:49-57. [DOI: 10.1016/j.pbb.2015.09.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 09/09/2015] [Accepted: 09/11/2015] [Indexed: 12/01/2022]
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26
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Baba S, Enomoto T, Horisawa T, Hashimoto T, Ono M. Blonanserin extensively occupies rat dopamine D3 receptors at antipsychotic dose range. J Pharmacol Sci 2015; 127:326-31. [PMID: 25837930 DOI: 10.1016/j.jphs.2015.01.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Revised: 01/04/2015] [Accepted: 01/22/2015] [Indexed: 12/14/2022] Open
Abstract
Antagonism of the dopamine D3 receptor has been hypothesized to be beneficial for schizophrenia cognitive deficits, negative symptoms and extrapyramidal symptoms. However, recent animal and human studies have shown that most antipsychotics do not occupy D3 receptors in vivo, despite their considerable binding affinity for this receptor in vitro. In the present study, we investigated the D3 receptor binding of blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptors antagonist, in vitro and in vivo. Blonanserin showed the most potent binding affinity for human D3 receptors among the tested atypical antipsychotics (risperidone, olanzapine and aripiprazole). Our GTPγS-binding assay demonstrated that blonanserin acts as a potent full antagonist for human D3 receptors. All test-drugs exhibited antipsychotic-like efficacy in methamphetamine-induced hyperactivity in rats. Treatment with blonanserin at its effective dose blocked the binding of [(3)H]-(+)-PHNO, a D2/D3 receptor radiotracer, both in the D2 receptor-rich region (striatum) and the D3 receptor-rich region (cerebellum lobes 9 and 10). On the other hand, the occupancies of other test-drugs for D3 receptors were relatively low. In conclusion, we have shown that blonanserin, but not other tested antipsychotics, extensively occupies D3 receptors in vivo in rats.
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Affiliation(s)
- Satoko Baba
- Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan
| | - Takeshi Enomoto
- Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
| | - Tomoko Horisawa
- Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan
| | - Takashi Hashimoto
- Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan
| | - Michiko Ono
- Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan
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27
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Kalariya PD, Patel PN, Sharma M, Garg P, Srinivas R, Talluri MVNK. Characterization of stress degradation products of blonanserin by UPLC-QTOF-tandem mass spectrometry. RSC Adv 2015. [DOI: 10.1039/c5ra10641a] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Forced degradation study of blonanserin and structural elucidation of its degradation products was performed using high resolution tandem mass spectrometry.
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Affiliation(s)
- Pradipbhai D. Kalariya
- Department of Pharmaceutical Analysis
- National Institute of Pharmaceutical Education & Research
- IDPL R&D Campus
- Hyderabad-500 037
- India
| | - Prinesh N. Patel
- Department of Pharmaceutical Analysis
- National Institute of Pharmaceutical Education & Research
- IDPL R&D Campus
- Hyderabad-500 037
- India
| | - Mahesh Sharma
- Department of Pharmacoinformatics
- National Institute of Pharmaceutical Education and Research (NIPER)
- Mohali
- India
| | - Prabha Garg
- Department of Pharmacoinformatics
- National Institute of Pharmaceutical Education and Research (NIPER)
- Mohali
- India
| | - R. Srinivas
- Department of Pharmaceutical Analysis
- National Institute of Pharmaceutical Education & Research
- IDPL R&D Campus
- Hyderabad-500 037
- India
| | - M. V. N. Kumar Talluri
- Department of Pharmaceutical Analysis
- National Institute of Pharmaceutical Education & Research
- IDPL R&D Campus
- Hyderabad-500 037
- India
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