Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment
Masataka WadaYoshihiro NodaYusuke IwataSakiko TsugawaKazunari YoshidaHideaki TaniYoji HiranoShinsuke KoikeDaiki SasabayashiHaruyuki KatayamaEric PlitmanKazutaka OhiFumihiko UenoFernando CaravaggioTeruki KoizumiPhilip GerretsenTakefumi SuzukiHiroyuki UchidaDaniel J. MüllerMasaru MimuraGary RemingtonAnthony A. GraceAriel Graff‐GuerreroShinichiro Nakajima
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Clozapine is the first and most effective atypical antipsychotic drug for treatment-resistant schizophrenia (TRS). After withdrawal of clozapine due to concerns of agranulocytosis, clozapine was reintroduced with a comprehensive safety monitoring system, the clozapine patient monitoring system (CPMS). The reintroduction was a response to the pressure from psychiatrists and patients with TRS and their families. Clozapine is still the best single agent for the treatment of TRS. However, approximately 30% of patients with TRS still show psychotic symptoms. In patients with clozapine-resistant schizophrenia (CRS), augmentation of other antipsychotic agents could be considered after a thorough evaluation of proper clozapine treatment. In this review, the status of clozapine in patients with TRS and CRS will be discussed. Key Words: Antipsychotics · Clozapine · Schizophrenia · Treatment-resistant schizophrenia ì¤ì¬ ë¨ì´: ì¡°íë³ Â· ì¹ë£ì íì± ì¡°íë³ Â· í´ë¡ìí · íì ì ë³ì½ë¬¼
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Deep Brain Stimulation (DBS) is a developing therapeutic technique with a high potential to control and treat central nervous system diseases through neuromodulation. DBS utilizes through implanted electrodes that are inserted in the targeted brain structure. Being an emerging technology; neuromodulation introduces many challenges that are not yet comprehensively identified, characterized and resolved. The advancement of this technique requires qualitative and quantitative perception of the brain response to electrical stimulation which is controlled by the electric field distribution within the brain tissue. This can be realized by formulating the tissue-field interaction such that we will have a better understanding of the spatial extent and the direct effects of deep brain stimulation (DBS) on neurons activity. The focus of this research is to develop a model for encoding and decoding the neuron activity in the DBS region and to address all the parameters that affect this activity in order to have a complete understanding of the DBS problem and to develop a brain model that can be readily used in DBS analysis. Our goal is to study the immediate direct effects of the stimulating field and examine where the beneficial effects of DBS originate since the mechanism of DBS is not yet fully understand and hence an inclusive comprehensive performance study will be done for the DBS problem.
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Objective:To study the stability of plasma clozapine concentration in patients taking clozapine chronically and the related factors.Method:Plasma clozapine concentration was measured three times in 305 inpatients with schizophrenia who had taken clozapine for more than one year.Results:There was a fluctuation in level of plasma clozapine between the three times,that is,210 cases more than 20.0%,among them 127 cases more than 25.0%,50 cases more than 50.0%,7 cases more than 100.0%,among them 1 case more than 404.2%.The stability of plasma clozapine concentration was correlated to gander,smoking,combined drugs taking and dosage of clozapine and so forth.Conclusion:Plasma clozapine concentration of those patients who had taken clozapine chronically may change by gander,smoking,combined drugs taking and dosage of clozapine.
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Clozapine is the only antipsychotic with proven efficacy in treatment-resistant schizophrenia, but some life-threatening side effects limit its use. Here we report a patient with clozapine-induced myocarditis and successful rechallenge. The patient still uses clozapine and has not developed myocarditis over 36 months of observation. It may be possible to use clozapine even after myocarditis and thus improve symptoms and functionality of schizophrenia patients.
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治療抵抗性の統合失調症患者を対象に,clozapine 治療が抗精神病薬の頓用使用に 及ぼす影響について検討した。対象は,clozapine 治療開始前に慈圭病院に26週間以上入 院していた治療抵抗性統合失調症患者で,2017 年9月 30日までに clozapine を処方開始し た症例とした。抗精神病薬の頓用使用が 7 日間全くない週を無頓用週と定義して, clozapine 開始前後26週間(合計52週間)でその頻度を評価した。さらに,無頓用週以外 に,隔離あるいは拘束期間や,閉鎖あるいは開放病床使用期間,外来期間に関しても週単 位で評価した。結果,45例が研究対象となった。Clozapine 療法によって,無頓用週は有 意に増加し,その増加は投与後 5 週目には明らかになった。対象45例全体では,隔離や 拘束があった週が減少傾向を示し,開放病床を利用した週が有意に増加した。今回指標に 用いた無頓用週は,症状改善の指標というよりは病状の安定化の指標であり,本研究から clozapine の使用によって症状の安定化が投与後約 1 ヵ月頃から得られることが示唆され た。 臨床精神薬理 23:1029-1040, 2020 Key words ::clozapine, effectiveness, retrospective, treatment-resistant schizophrenia
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Deep brain stimulation (DBS) refers to a neurosurgical process in which electrical stimulation is delivered via electrodes implanted within deep brain regions. DBS has become the most established clinical therapy for patients with movement disorders, although recent studies have investigated its application in a broad range of neurological and psychiatric disorders as well. Moreover, DBS has proven effective in controlling symptoms in patients with Parkinson's disease (PD). While early DBS systems were capable of stimulation only, technological advancements have allowed for the direct assessment of dysfunctional brain activity and subsequent stimulation of the pathological circuitry. DBS can also be combined with neurochemical stimulation to address decreased concentrations of dopamine in the brain. Given that both electrical and neurochemical treatments for PD aim to rectify abnormalities in neural activity, the general term "neuromodulation" is considered more accurate and comprehensive. Recent improvements in signal detection and information processing techniques have provided further insight into PD mechanisms, which may aid in the development of personalized biomarkers and in the prediction of symptoms. In this comprehensive review, we discuss various aspects of neuromodulation in patients with PD, including basic theories, stimulation paradigms, and current challenges in the field.
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