臺灣博碩士論文加值系統

研究背景：
雖然血清素回收抑制劑(Serotonin reuptake inhibitors，SRIs)是目前治療強迫症的首選藥物，仍有高達40–60%患者的強迫症狀對現有藥物治療的療效不彰。神經影像學及基因研究顯示大腦皮質-紋狀體及視丘迴路的麩氨酸傳導路徑功能失調與強迫症的相關性。N-methylglycine (sarcosine)是一種內生性的甘氨酸運輸子抑制劑(Glycine transporter I inhibitor)，作用在麩氨酸神經聯會(glutamatergic synapes)調節NMDA受體的神經傳導。本研究在探討sarcosine是否能改善強迫症症狀。

研究方法：
此先驅開放性研究中，我們使用sarcosine治療強迫症患者。起始劑量每日1000mg，增加至每日2000mg共治療十週。以耶魯布朗強迫量表、漢氏焦慮量表、漢氏憂鬱量表及臨床整體印象評估臨床症狀改變。

研究結果：
九名完成試驗之受試者包括單獨服用sarcosine者五名（三名曾用過血清素回收抑制劑，兩名從未用過藥物治療），sarcosine合併使用中的SRIs者四名。研究個案群為中至高嚴重度強迫症患者。sarcosine對未曾用過任何藥物治療的兩名個案有明顯療效，且症狀在用藥兩週內即有明顯改善。在使用過或維持SRIs治療之個案，sarcosine之療效則不一致：併用SRIs治療四位中，兩位血清素回收抑制劑頑抗型(SRIs-refractory)個案對sarcosine無明顯療效；另一位併SRI治療個案在用藥兩週內強迫症狀即有明顯改善，但在服藥劑量減少兩週後症狀惡化。

結論：
未來可以進行雙盲對照研究比較sarcosine與SRIs的療效，並收集個案週邊血液測試其基因型和治療前後基因表現、並結合神經影像學研究，以進一步了解麩氨酸神經傳導在強迫症之致病因與治療的意義。

Background : Although serotonin reuptake inhibitors (SRIs) are the medications of choice for obsessive compulsive disorder (OCD), only 40-60% of patients respond to a single trial of any of these agents. Usually, the maximum response is only partial. Hyperactivity in cortico–striatal -thalamic circuits of the brain in patients with OCD may be due to an imbalance between tonic and phasic glutamatergic release in striato-pallidal pathways. The associations of glutamatergic transmission with OCD had been implicated by evidences from families’ studies with genomic scan and genetic polymorphism studies on N-methyl-D-aspartate receptor (NMDA-R) subunits. N-methylglycine (sarcosine) is an endogenous antagonist of glycine transporter-1, which potentiates glycine''s action on NMDA-R glycine site. In this open label study, we investigated the efficacy of sarcosine in treatment of OCD.
Method : Nine psychiatric outpatients aged between 20 and 63 with a primary diagnosis of OCD had completed 10 weeks’ treatment with sarcosine. Five of them received sarcosine as mono-therapy and 4 of them as an adjuvant to their current SRIs therapies. Yale–Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale (HAM-D), and Hamilton Anxiety Rating Scale (HAM-A) scores were obtained biweekly.
Result: Y-BOCS scores improved significantly over time in two drug-naïve patients and a patient with combination treatment. There was no significant improvement in Y-BOCS scores in patients who failed more than 2 standard treatments with SRIs. For responders, the time intervals to achieve criteria of response (more than 35% decrease of Y-BOCS scores) were within 2 weeks of sarcosine treatment at relatively low dose.
Conclusion: In the future, double blind, placebo controlled trials comparing the clinical efficacies between sarcosine and an SRI, in combination with genetic studies focusing on the glutamatergic neurotransmission, is suggested.

目錄
第一章 前言 1
第一節 研究背景 1
(一)強迫症造成的問題以及醫療保健的重要性 1
(二)強迫症的臨床表現呈現異質性 2
(三)強迫症藥物治療遭遇的困境與發展需求 3
(四)強迫症的異質性與藥物療效的預測因子 5
(五)麩氨酸神經傳導(Glutamatergic Neurotransmission)
於強迫症扮演的角色 6
(六)是否能調節NMDA-R神經傳導來治療強迫症 10

第二節 研究目的 11

第二章 研究方法 12
第一節 研究對象及工具 12
(一) 評量工具 13
(二) 收案標準 15
(三) 排除標準 16
第二節 研究設計 17
(一) 評估項目 17
(二)給藥治療方式 18

第三章 研究結果 19

第四章 討論 23
第一節 結果討論 23
第二節 研究限制 27
(一)研究設計與方法 27
(二)研究用藥 29

第五章 結論 30

參考文獻 31


圖表目錄
表、一 41
表、二 42
圖、一 43

附錄 44

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