認知行為治療與重複經顱磁刺激在酒精使用疾患治療中的安慰劑效應：系統性文獻回顧與統合分析

Abstract

背景：酒精使用疾患（Alcohol Use Disorder, AUD）是一種常見且具高度臨床負擔的精神疾病，對個人健康與整體社會都造成深遠的影響。雖然已有幾種治療藥物上市，但臨床療效有限，復發率也偏高。相較之下，非藥物性治療，如認知行為治療（Cognitive Behavioral Therapy, CBT）與重複經顱磁刺激（Repetitive Transcranial Magnetic Stimulation, rTMS）在降低酒精使用與渴求方面，則顯示出有相當治療效果的潛力。然而這兩種治療方式的「安慰劑效應」少有研究深入探討，若不設法釐清，相關治療成效的真實性將持續遭遇質疑。 目的：本研究目的在於系統性地整理並統合分析CBT與rTMS在研究治療AUD患者時的安慰劑效應強度，並進一步探討臨床試驗中不同的研究情境與設計因素可能帶來的影響。 方法：研究團隊自文獻資料庫最早涵蓋年份至2025年6月1日，系統性搜尋主要國際文獻資料庫，納入具有假性治療組（sham group）或安慰劑組（placebo group）的隨機對照試驗（Randomized Controlled Trials, RCTs）。使用隨機效應模型整合placebo/sham組介入前後的標準化平均差（dav），並依介入方式、治療時間、盲法設計、地區及AUD療效指標進行分層分析。為驗證結果穩定性，也進行逐一排除（leave-one-out）與排除不具盲法或具發表偏倚研究的敏感性分析。 結果：最終一共納入14篇符合條件的RCT文章，包含8篇CBT研究與6篇rTMS研究。統合分析結果顯示：CBT placebo組的AUD相關症狀有顯著改善（dav = –0.67，95% 信賴區間：–0.94 至 –0.40），而rTMS sham組雖呈現更大的變化幅度，但未達統計顯著（dav = –3.52，95% 信賴區間：–8.53 至 1.49）。進一步的分層與統合迴歸分析指出，治療是否具有專業引導、介入時間長短、盲法設計以及AUD相關結果選擇，皆可能影響安慰劑效應的強度。敏感性分析結果則支持主要分析的穩定性。 結論：本研究發現CBT與rTMS的安慰劑效應會隨情境而異，反映了患者的期望與參與研究對治療結果的影響，而非僅源於研究設計上的差異。此結果提醒了我們，在評估非藥物方法治療AUD療效時，應注意非特異性的心理因素，並在設計未來進一步研究與臨床治療時，將安慰劑效應納入考量。

Background: Alcohol use disorder (AUD) is a widespread mental disorder with tremendous burdens to human society. Although pharmaceutical treatments have developed, overall efficacy is not satisfying, and relapse rates persist high. Alternatively, non-pharmacological treatments, including cognitive behavioral therapy (CBT) and repetitive transcranial magnetic stimulation (rTMS), have shown promising potential in reducing alcohol use and craving. Yet, the potential role of placebo effects in these interventions remains unexplored. Objective: To systematically review literature and summarize the magnitude of placebo effects for either CBT or rTMS in treating individuals with AUD and to elucidate related contextual factors in trials. Methods: Major literature databases were searched from their inception to June 1st, 2025, to identify randomized controlled trials (RCTs) incorporating sham or placebo comparators. Standardized mean differences (dav) before and after interventions in the placebo/sham groups were pooled using random-effects models. Subgroup analyses were performed according to intervention type and duration, application of blindness, geographical region, and outcome measurement tool. Sensitivity analyses, including leave-one-out procedures and exclusion of open-label or publication-biased studies, were conducted to assess their robustness. Results: Fourteen eligible RCTs were identified, comprising eight CBT and six rTMS studies with a well-conducted placebo or sham arm. The pooled effect of placebo CBT indicated a significant reduction in AUD-related outcomes (dav = –0.67, 95% CI: –0.94, –0.40), while rTMS sham arms demonstrated a larger but non-significant placebo effect (dav = –3.52, 95% CI: –8.53, 1.49). Subgroup and meta-regression analyses suggested that intervention guidance, duration, blindness, and outcome measurement tool may influence the magnitude of placebo effects. Sensitivity analyses further supported the robustness of estimating placebo effects. Conclusion: Placebo effects observed in CBT and rTMS appeared to vary across different contexts, reflecting how patients’ expectations and therapeutic engagement influence the effectiveness of AUD treatment. These findings highlighted the importance of considering non-specific psychological issues when interpreting treatment outcomes in practice and designing future intervention studies for AUD.