2014-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/651261摘要：早期即介入精神分裂症應可得較佳療效，然除正性症狀療效較明顯，未能有好的治療處理認知缺損及負性症狀等障礙。Memantine，一種非競爭型 NMDA glutamate 受器拮抗劑，過去用於改善阿茲海默症之認知功能，也可能對精神分裂症有益。過去僅少數證據顯示 memantine 輔助治療可改善患者的症狀，但較大樣本的研究則未見明顯效果。本研究使用 memantine 於急性期緩解後之精神分裂症患者，檢視其效果和安全性，非僅重覆先前之研究，更關注對於認知功能及負性症狀的效果，並將病程長度視為重要解釋變項。門診年齡 18 至 45 歲間，不論性別，正穩定接受第二代抗精神病劑治療之患者。排除曾嚴重復發、目前正性症狀分數過高，及有其他會影響認知功能之疾患。臨床以正負性症狀量表、臨床整體印象、憂鬱症狀量表評估；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。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。於第 1、2、4、8、12 週回診接受臨床、個人社會功能評量、藥物滿意度、及副作用評估。結束時再測一次心理功能。每組預定收治 40 名，計 120 名。將確保至少三分之一個案的病程在 5年以內。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, while only limited evidence from randomized clinical trials hasdemonstrated its efficacy and a large sample sized study failed to show any impact. This studywill use memantine as an adjuvant agent on their existing antipsychotic treatment for patientswith schizophrenia while their positive symptoms subsided to examine its efficacy and safety.Not only to replicate previous studies, this study will have specific interests in its impact oncognitive functioning and negative symptoms, and taking duration of illness as an importantcovariate.Both male and female aged 18–45 years old outpatients, currently receiving treatment byatypical antipsychotics in a relatively stable condition will be recruited. Patients with a currentscore of 5 or more on any of or scores 4 on 3 or more of the 7 positive symptom item on thePositive and Negative Symptom Scale (PANSS) and concurrent psychiatric or medicalcondition with impact on cognition are excluded. Clinical severity will be rated by PANSS,Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression ofImprovement (CGI-I), and Hamilton Rating Scale for Depression (HRS-D). A set ofneurocognitive battery including continuous performance test (CPT), Wisconsin Card SortingTest (WCST), Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), Trail MakingTests, Mandarin version of Verbal Fluency Test and Wechsler Memory Scale-Third Edition(WMS-III) will be done.A randomized double-blind placebo-controlled trial is employed to test two differentdosages, 10 or 20 mg/day, of memantine add-on compared to placebo on each group for 12weeks. Participants will be rated with PANSS, CGI, HRS-D, Personal and SocialPerformance scale, medication satisfaction, and adverse events at week 1, 2, 4, 8, 12 duringfollow-up. Neurocognitive functioning will be measured at baseline and the end of the trial.We plan to recruit 40 patients for each arm with a total of 120 participants. We will try ourbest to ensure at least one third of them are in their first 5 years of illness. All efficacyanalyses will be performed based on the intent-to-treat population with missing data beingimputed using the last observation carried forward (LOCF) approach. The key outcomevariable of interest is the improvement in cognitive functioning and negative symptoms.輔助療法認知缺損病程長度glutamate 假說memantine負性症狀精 神分裂症adjuvant therapycognitive deficitsduration of illnessglutamate hypothesismemantinenegative symptomsschizophrenia