臺灣博碩士論文加值系統

背景
廣泛性焦慮症是一種重要且常見的精神疾病，其盛行率為3.7%。廣泛性焦慮症的主要治療包括心理治療、藥物和自助治療。雖然治療方式很多，但目前很少系統性的研究，比較不同治療放式哪者最為有效。因此，這項研究的目的是執行一個有效的隨機對照試驗網絡綜合統計分析(network meta-analysis)，統整直接和間接的證據，分析廣泛性焦慮症各治療方式的效果。

方法
我們搜索了四主要書目資料庫，Cochrane Central Register of Controlled Trials，Embase，PsycINFO 和 PubMed，納入成年廣泛性焦慮症的隨機對照試驗，並允許所有併發症。我們排除了研討會的摘要和論文，以及研究重點是難治型病人的試驗。我們從已發佈的文獻中提取資料，對不同治療與安慰劑之間的比較治療效果進行了標準化平均差(standardized mean difference)的計算，估計了所有治療的排名概率以及曲線下表面累計排名（surface under the cumulative ranking curve）。

結果
最後網絡綜合統計分析共納入91篇文獻(14812名受試者)。結果顯示，norepinephrine–dopamine reuptake inhibitor(標準化平均差 -1.84, 95%信賴區間 -3.05 to -0.62)，noradrenergic and specific serotonergic antidepressant(-0.91, -1.62 to -0.20)，melatonergic receptor agonist(-0.68, -1.15 to -0.21)，selective serotonin reuptake inhibitor(SSRI; -0.67, -0.90 to -0.43)，azapirone(-0.58, -1.0 to -0.17)，anticonvulsant(-0.56, -0.85 to -0.28)，serotonin–norepinephrine reuptake inhibitor(SNRI; -0.54, -0.79 to -0.30)，和 benzodiazepine(BZD; -0.40, -0.65 to -0.15)比安慰劑有顯著效果。大多數心理和自助治療比等待組(waitlist)有顯著的效果；然而，在心理治療和心理安慰劑之間沒有明顯的差異。

結論
大多數的藥物治療和心理治療比安慰劑和控制組有顯著的效果。SSRI、SNRI、buspirone、pregabalin和BZD比其他治療可能更有效。Agomelatine可能是治療廣泛性焦慮症的有效藥物。大多數心理治療和自助治療比等待組有顯著的效果；然而，因為等待組可能是一個反安慰劑(nocebo)，這可能高估了心理治療和自助治療的療效。雖然自助治療的效果不如藥物或心理治療，但它具有方便性和無藥物副作用的優點。整體來說，大多數的藥物治療比心理治療有更好的效果，多數心理治療比自助治療有更好的效果。

Background
Generalized anxiety disorder (GAD) is a significant and common type of mental illness, which had a lifetime prevalence of 3.7%. Main interventions/treatments for GAD include psychotherapy, medications and self-help interventions. Regardless of the complexity of treatment decisions for GAD, there have been very few studies conducted on systematic comparisons of varying intervention works. Thus, the aim of this study is to perform a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative interventions for GAD.

Methods
We searched four major bibliographic databases, Cochrane Central Register of Controlled Trials, Embase, PsycINFO and PubMed for the published studies of RCTs of adult patients with a diagnosis of GAD, and allowed for all comorbidities. We excluded the congress abstracts and dissertations, and the studies focusing on adjunctive therapies for treatment-refractory patients or patients having a history of inadequate treatment response. We extracted data from published reports. The standardized mean difference (SMD) was further calculated for the comparative treatment effects between each intervention and placebo. The ranking probabilities for all interventions were estimated and the hierarchy of each intervention was summarized as surface under the cumulative ranking curve.

Results
A total of 91 articles (14812 participants) were identified in the final NMA. The results showed that norepinephrine–dopamine reuptake inhibitor (SMD -1.84, 95% credible interval -3.05 to -0.62), noradrenergic and specific serotonergic antidepressant (-0.91, -1.62 to -0.20), melatonergic receptor agonist (-0.68, -1.15 to -0.21), selective serotonin reuptake inhibitor (SSRI; -0.67, -0.90 to -0.43), azapirone (-0.58, -1.0 to -0.17), anticonvulsant (-0.56, -0.85 to -0.28), serotonin–norepinephrine reuptake inhibitor (SNRI; -0.54, -0.79 to -0.30), and benzodiazepine (BZD; -0.40, -0.65 to -0.15) had greater effects than placebo. Most psychological and self-help interventions had greater effects than the waitlist group. However, no significant differences could be found between psychological interventions and psychological placebo.

Conclusion
Most pharmacological and psychological interventions were more effective for the GAD treatment than placebo and control condition. SSRI, SNRI, buspirone, pregabalin and BZD were more likely to have treatment effectiveness than others. Agomelatine might be a potential effective medication for treatment of GAD. Most psychotherapies and self-help intervention had greater effect than waitlist; however, these might overestimate their therapeutic effects since waitlist could be a nocebo. Although the effect size of self-help intervention was not as good as pharmacological or psychological interventions, it has the advantages of convenience and lack of the side effects from medication. Overall, most pharmacological interventions had larger effect sizes than psychological interventions, and most psychological interventions showed larger effect sizes than self-help intervention.

誌謝 ⅰ
中文摘要 ⅱ
英文摘要 ⅳ
目錄 ⅶ
圖目錄 ⅷ
表目錄 ⅸ
第一章 緒論(Introduction) 1
第二章 研究設計與方法(Methods) 2
第一節 篩選標準(Search strategy and selection criteria) 2
第二節 統計分析(Statistical analysis) 3
第三章 結果(Results) 4
第四章 討論(Discussion) 7
第一節 藥物治療(Pharmacological interventions) 7
第二節 心理和自助治療(Psychological and self-help interventions) 10
第三節 合併治療(Combined therapy) 11
第五章 研究限制(Limitation) 11
第六章 結論(Conclusion) 12
Figure 1: PRISMA flowchart 14
Figure 2: Network diagram for efficacy analysis representing direct comparisons among classes 15
Figure 3: Interval plot of treatment effects of classes of interventions compared with placebo 16
Figure 4: Effect sizes of classes of treatments in pairwise comparisons 17
Table 1. General characteristics of eligible studies included in the network meta-analysis 18
Table 2. Ranking probability of the pharmacological and psychological interventions for GAD 19
參考文獻 20
附錄 23

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