2013-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/651262摘要：早期即介入精神分裂症被認為可得較佳療效，然除正性症狀治療反應較明顯外，仍未能有好的治療來處理認知缺損及負性症狀等功能障礙。Memantine，一種非競爭型NMDA glutamate 受器拮抗劑，主要用於改善阿茲海默症之認知功能，也可能對精神分裂症之認知功能有益。過去 memantine 曾被用在慢性精神分裂症患者未見明顯效果，本研究則鎖定首次發病之精神分裂症患者，於其急性症狀緩解後仍有認知功能退化或負性症狀，來檢視此輔助療法的效果和安全性。收案對象為男女不拘，年齡 18 至 45歲之門診發病 5年內，正穩定接受第二代抗精神病劑治療之患者。排除病程中曾嚴重復發、目前正性症狀評分有任一項大於 4分或有三項以上評為 4分者，以及有其他精神科或內外科會影響其認知功能之疾患者。臨床評估包括正負性症狀量表、臨床整體印象分數、憂鬱症狀量表；心理功能評估有持續注意力、威斯康辛分類、連線、魏氏智力及語文流暢和記憶測驗。除繼續使用原有藥物外，隨機分配為接受 memantine 每日 10 毫克、20 毫克、或安慰劑三組，進行為期 12 週的輔助治療。受試者每兩週回診接受臨床評估、個人社會功能評量、藥物滿意度、及副作用評估。試驗結束時再測一次心理功能。每組預定收治 40 名，共計 120 名。所有療效以意圖治療分析法及最後觀察用向前法分析，主要依變項為認知功能及負性症狀改善程度。<br> Abstract: Intervention from the early stage of schizophrenia is a promising approach to get bettertreatment response, but functioning decline related to cognitive impairments and negativesymptoms tend to last after the positive symptoms get subsided while currently no therapy hasbeen shown to be effective for treating these problems. Memantine, an uncompetitiveantagonist of glutamate receptors of the N-methyl-D-aspartate type previously approved ascognitive enhancer forAlzheimer’s disease, is a potential candidate for preventing cognitivedecline of schizophrenia, although previous randomized clinical trials failed to demonstrate itsefficacy on chronic schizophrenic patients. This study will target at a population of firstepisode schizophrenia with their positive symptoms subsided yet still showing cognitivedecline and/or negative symptoms, use memantine as an adjuvant agent on their existingantipsychotic therapy, and examine its efficacy and safety. Both male and female aged 18–45years old outpatients with a length of illness for less than 5 years since first diagnosed asschizophrenia, currently receiving treatment by atypical antipsychotics in a relatively stablecondition will be recruited. Patients with a major relapse during the illness, a current score of5 or more on any of or scores 4 on 3 or more of the 7 positive symptom item on the Positiveand Negative Symptom Scale (PANSS) and concurrent psychiatric or medical condition withimpact on cognition are excluded. Clinical severity will be rated by PANSS, Clinical GlobalImpression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I), andHamilton Rating Scale for Depression (HRS-D). A set of neurocognitive battery includingcontinuous performance test (CPT), Wisconsin Card Sorting Test (WCST), Wechsler AdultIntelligence Scale-Third Edition (WAIS-III), Trail Making Tests, Mandarin version of VerbalFluency Test and Wechsler Memory Scale-Third Edition (WMS-III) will be done. Arandomized double-blind placebo-controlled trial is employed to test two different dosages,10 or 20 mg/day, of memantine add-on compared to placebo on each group for 12 weeks.Participants will be rated biweekly during follow-up, including Personal and SocialPerformance scale, medication satisfaction, and adverse events. Neurocognitive functioningwill be measured at baseline and the end of the trial. We plan to recruit 40 patients for eacharm with a total of 120 participants. All efficacy analyses will be performed based on theintent-to-treat population with missing data being imputed using the last observation carriedforward (LOCF) approach. The key outcome variable of interest is the improvement incognitive functioning and negative symptoms.輔助療法認知缺損初發精神分裂症glutamate 假說memantine負性症 狀adjuvant therapycognitive deficitsfirst episode schizophreniaglutamate hypothesismemantinenegative symptoms