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Nagai N.,Yamanashi Prefectural Kita Hospital
Nihon rinsho. Japanese journal of clinical medicine | Year: 2013

Olanzapine is one of the SGAs (second-generation antipsychotics) which have been used for the treatment of patients with schizophrenia and bipolar disorder in Japan. Olanzapine has various affinities for multiple receptors, including dopamine D2 receptor, serotonin 5-HT2A, 5-HT2C, 5-HT6 receptors, and adrenaline alpha1, histamine H1, muscarine M1-M5 receptors as well. Therefore, olanzapine is known as MARTA(multi-acting receptor targeted antipsychotics). Numerous studies have been conducted to compare the effectiveness of olanzapine between SGAs and FGAs (first-generation antipsychotics). According to the head-to-head meta-analysis and large-scale studies like CATIE and EUFEST, olanzapine seems to have not only higher efficacy but also less discontinuation comparing to other anti-psychotics. Source

Ishigooka J.,Tokyo Womens Medical University | Nakamura J.,University of Occupational and Environmental Health Japan | Fujii Y.,Yamanashi Prefectural Kita Hospital | Iwata N.,Aichi University | And 5 more authors.
Schizophrenia Research | Year: 2015

Objective: This study was designed to evaluate efficacy and safety of aripiprazole once-monthly (AOM) by verifying non-inferiority of AOM to oral aripiprazole in Asian patients with schizophrenia. Method: The study consisted of a screening phase and three phases: an oral conversion phase (≤ 12 weeks), an oral stabilization phase (≤ 12 weeks) and a 52-week double-blind phase. Patients meeting stabilization criteria for 4. weeks during the oral stabilization phase were randomly assigned (1:1) to AOM (400. mg) or oral aripiprazole (6-24. mg/day). The primary endpoint was Kaplan-Meier estimated rate of non-exacerbation of psychotic symptoms/non-relapse at Week 26. Results: A total of 724 patients were screened, and 502 patients entered the oral stabilization phase. Of 455 patients randomized in the double-blind phase, 228 received AOM and 227 received oral aripiprazole. The non-exacerbation of psychotic symptoms/non-relapse rates at Week 26 were 95.0% (AOM) and 94.7% (oral aripiprazole) and the difference was 0.3% (95% CI: - 3.9,4.5), thus non-inferiority of AOM compared to oral aripiprazole with respect to non-exacerbation of psychotic symptoms/non-relapse rate was shown with a margin of - 3.9% which is well above the pre-defined non-inferiority limit (- 15%). The proportions of patients meeting exacerbation of psychotic symptoms/relapse criteria and stabilization of psychotic symptoms/maintenance criteria were 6.6% and 92.5% in both groups. Discontinuation rates due to all reasons were 25.9% (AOM) and 33.5% (oral aripiprazole). AOM was well tolerated as well as oral aripiprazole. Conclusions: Non-inferiority of AOM to oral aripiprazole was established. AOM is efficacious in maintenance treatment of stabilized schizophrenia, with comparable efficacy and tolerability to oral aripiprazole. Clinical Trials Registration: JapicCTI-101175. © 2014 Elsevier B.V. Source

Misawa F.,Yamanashi Prefectural Kita Hospital | Shimizu K.,Yamanashi Prefectural University | Fujii Y.,Yamanashi Prefectural Kita Hospital | Miyata R.,Yamanashi Prefectural Kita Hospital | And 8 more authors.
BMC Psychiatry | Year: 2011

Background: Although the validity and safety of antipsychotic polypharmacy remains unclear, it is commonplace in the treatment of schizophrenia. This study aimed to investigate the degree that antipsychotic polypharmacy contributed to metabolic syndrome in outpatients with schizophrenia, after adjustment for the effects of lifestyle.Methods: A cross-sectional survey was carried out between April 2007 and October 2007 at Yamanashi Prefectural KITA hospital in Japan. 334 patients consented to this cross-sectional study. We measured the components consisting metabolic syndrome, and interviewed the participants about their lifestyle. We classified metabolic syndrome into four groups according to the severity of metabolic disturbance: the metabolic syndrome; the pre-metabolic syndrome; the visceral fat obesity; and the normal group. We used multinomial logistic regression models to assess the association of metabolic syndrome with antipsychotic polypharmacy, adjusting for lifestyle.Results: Seventy-four (22.2%) patients were in the metabolic syndrome group, 61 (18.3%) patients were in the pre-metabolic syndrome group, and 41 (12.3%) patients were in visceral fat obesity group. Antipsychotic polypharmacy was present in 167 (50.0%) patients. In multinomial logistic regression analyses, antipsychotic polypharmacy was significantly associated with the pre-metabolic syndrome group (adjusted odds ratio [AOR], 2.348; 95% confidence interval [CI], 1.181-4.668), but not with the metabolic syndrome group (AOR, 1.269; 95%CI, 0.679-2.371).Conclusions: These results suggest that antipsychotic polypharmacy, compared with monotherapy, may be independently associated with an increased risk of having pre-metabolic syndrome, even after adjusting for patients' lifestyle characteristics. As metabolic syndrome is associated with an increased risk of cardiovascular mortality, further studies are needed to clarify the validity and safety of antipsychotic polypharmacy. © 2011 Misawa et al; licensee BioMed Central Ltd. Source

Ikai S.,Yamanashi Prefectural Kita Hospital | Ikai S.,Keio University | Suzuki T.,Keio University | Uchida H.,Keio University | And 3 more authors.
Annals of Pharmacotherapy | Year: 2013

OBJECTIVE: To report on a patient who was successfully rechallenged with cloza - pine after perforation of the large intestine and pulmonary embolism post opera - tively, and provide a literature review on clozapine rechallenge. CASE SUMMARY: A 46-year-old Japanese man with treatment-resistant schizo - phrenia developed constipation and slight abdominal discomfort while taking clozapine 275 mg/day. He developed appendicitis, leading to perforation of the large intestine. During the postsurgery period, a partial embolism of the pulmonary artery was revealed. The patient's constipation was relieved when clozapine was discontinued, but other antipsychotics failed to control his delusions well. After thorough discussion, it was decided to rechallenge with clozapine. The low dose of clozapine 200 mg/day was tolerable for his delusion, and his constipation was managed with laxatives and exercises until 8 months after the accident. DISCUSSION: Clozapine is a gold standard medication in treatment-resistant schizophrenia but is associated with various adverse effects, some of which are life-threatening. Reintroduction of clozapine after severe adverse drug effects when other medications are not effective almost always poses a clinical dilemma for mental health professionals. A PubMed search (to January 25, 2013) using the key words clozapine and rechallenge found 50 articles. There were only sporadic positive case reports regarding the rechallenge after clozapine-related serious gastrointestinal problems. CONCLUSIONS: From the currently available evidence, most psychiatrists appear to avoid reintroduction of clozapine. However, the evidence is too weak to draw a definitive conclusion about reintroduction of this drug. Reintroduction of clozapine after initial adverse effects in patients with treatment-resistant schizophrenia may warrant case-by-case judgment, but needs to be further investigated. © 1967-2013 Harvey Whitney Books Co. All rights reserved. Source

Hatta K.,Juntendo University | Otachi T.,Gunma Psychiatric Medical Center | Fujita K.,Okehazama Hospital | Morikawa F.,Asahikawa Keisenkai Hospital | And 13 more authors.
Schizophrenia Research | Year: 2014

Purpose: We examined whether augmentation with olanzapine would be superior to switching to olanzapine among early non-responders (ENRs) to risperidone, and whether augmentation with risperidone would be superior to switching to risperidone among ENRs to olanzapine.We performed a rater-blinded, randomized clinical trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. ENRs to the initial antipsychotic (Clinical Global Impressions-Improvement Scale: ≥. 4 at 2. weeks) were allocated to receive either augmentation with or switching to the other antipsychotic (RIS. +. OLZ vs. RIS-OLZ; OLZ. +. RIS vs. OLZ-RIS). Results: Sixty patients who completed 2. weeks of risperidone treatment were divided into 33 early responders (RIS-ER) and 27 ENRs (RIS. +. OLZ, n. =. 14; RIS-OLZ, n. =. 13). Although time to treatment discontinuation for any cause was significantly shorter in RIS. +. OLZ group (54.1. days [95% confidence interval, 41.3-67.0]) than in RIS-ER group (68.7 [61.2-76.2]; P=. 0.050), it was not significantly shorter in RIS-OLZ group (58.5 [43.1-73.9]) than in RIS-ER group (P=. 0.19). Sixty patients who completed 2. weeks of olanzapine treatment were divided into 36 early responders (OLZ-ER) and 24 ENRs (OLZ. +. RIS, n. =. 11; OLZ-RIS, n. =. 13). Although time to treatment discontinuation for any cause was significantly shorter in OLZ-RIS group (56.1. days [40.7-71.5]) than in OLZ-ER group (74.9 [68.5-81.3]; P=. 0.008), it was not significantly shorter in OLZ. +. RIS group (64.6 [49.6-79.6]) than in OLZ-ER group (P=. 0.20). Conclusion: Despite the lack of pharmacokinetic investigation of dose adequacy in this study, it is possible that switching to olanzapine among ENRs to risperidone might have a small advantage over augmentation with olanzapine, while augmentation with risperidone might have a small advantage over switching to risperidone among ENRs to olanzapine. Further research is required before it would be appropriate to modify routine practice in the direction of these findings. © 2014. Source

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