注意缺陷多動障礙的藥物干預：一項系統評價與劑量-效應網絡薈萃分析 Pharmacological interventions for ADHD: a systematic review and dose–effect network meta-analysis ——《柳葉刀 / 精神病學》第13卷，第6期，2026年6月—— <The Lancet / Psychiatry> Volume 13, Issue 6, June 2026 【摘要】背景：優化ADHD（注意缺陷多動障礙）藥物治療劑量是最大化療效的關鍵，然而大多數臨床指南對此提供的指導信息有限。儘管人們日益關注藥物劑量不足（低於治療有效劑量）的問題，但尚未針對所有ADHD藥物及各年齡段人群全面評估劑量-效應關係。本研究旨在估算ADHD藥物（包括興奮劑和非興奮劑）在不同年齡段人群中的療效與耐受性劑量-效應曲線。方法：我們對評估口服單藥治療（興奮劑和非興奮劑）的隨機雙盲對照試驗（RCT）進行了系統評價和劑量-效應網狀薈萃分析。納入對象為符合標準化ADHD診斷標準的5歲及以上個體。研究排除了涉及遺傳綜合徵、難治性人群或包含停藥期設計的研究。我們從MED-ADHD數據庫（更新於2025年2月17日）檢索符合條件的研究，未設語言限制，並納入了已發表及未發表的匯總數據。主要結局指標為療效（通過經臨床驗證的量表評估），次要結局指標為耐受性（因不良事件導致的停藥）。我們使用Cochrane偏倚風險評估工具（第2版）評估了研究內部的偏倚風險。利用包含限制性立方樣條（restricted cubic splines）的分層貝葉斯模型，我們總結了劑量與效應之間的關聯。針對兒童或青少年（<18歲）與成人（≥18歲）分別進行了分析。通過關鍵效應調節因素的分布情況，我們檢驗了網狀分析的傳遞性假設。具有ADHD親身經歷的人士參與了本研究的概念構思、設計以及結果解讀工作。研究方案已在OSF平台上預註冊。結果：我們在2017年的檢索中識別出9948篇潛在文獻，並在2025年2月17日的檢索中識別出5148篇文獻。在這總計15,096篇文獻中，8467篇在標題和摘要篩選階段被排除，另有5862篇在全文閱讀階段被排除。在剩餘的767份報告中，164份被納入系統評價，113項隨機對照試驗（RCT）（45項針對成人，68項針對兒童和青少年）被納入劑量-效應網狀薈萃分析。針對兒童和青少年的68項RCT共納入14,138名受試者（男性9,981人[70.6%]，女性4,157人[29.4%]），針對成人的45項RCT共納入11,016名受試者（男性5,958人[54.0%]，女性5,056人[46.0%]）。各RCT對種族或族裔數據的報告不一致。我們發現不同藥物類別和年齡組呈現出獨特的劑量-效應模式。在兒童和青少年中，哌甲酯、苯丙胺類藥物和胍法辛的療效中位數隨劑量增加而提升，分別在45毫克/天、25毫克/天和4毫克/天時達到峰值；儘管更高劑量下的估算值具有較寬的可信區間，但未發現更高劑量能帶來額外獲益的證據。在成人中，苯丙胺類藥物的療效在劑量超過約50毫克/天時出現平台期；而哌甲酯的療效持續增加，未見平台期，這可能歸因於數據稀缺。研究觀察到因不良事件導致停藥的可能性隨劑量增加而上升，具體表現為：苯丙胺類藥物（兒童劑量超過25毫克/天，成人超過50毫克/天）和哌甲酯（成人劑量超過50毫克/天；兒童未見明顯的劑量依賴性風險）。我們未發現托莫西汀（在固定劑量研究中）和莫達非尼存在劑量-效應模式的證據。多項敏感性分析證實了這些結果的穩健性。我們未發現存在非傳遞性（intransitivity）的證據。解讀：我們的研究結果對以下兩種做法提出了挑戰：一是“治療惰性”，即在療效不佳時未進一步調整劑量卻選擇維持現狀；二是盲目增加劑量至獲批上限以上，而此時潛在危害可能超過預期獲益。我們的研究結果可為臨床指南提供參考，並應支持關於ADHD藥物劑量的共同決策。 [Summary] Background: Optimising the dosage of pharmacological treatments for ADHD is key to maximising their benefits, yet most clinical guidelines provide only limited information on this issue. Dose–effect relationships have not been comprehensively assessed across all ADHD medications and age groups, despite growing concerns about subtherapeutic prescribing. We aimed to estimate dose–effect curves for efficacy and tolerability of ADHD medications (stimulants and non-stimulants) across age groups. Methods: We conducted a systematic review and dose–effect network meta-analysis of double-blind randomised controlled trials (RCTs) evaluating oral monotherapy (stimulants and non-stimulants) in individuals aged 5 years and older meeting standardised ADHD criteria. Studies involving genetic syndromes, treatment-resistant populations, or withdrawal-phase designs were excluded. We retrieved eligible studies from the MED-ADHD database, updated on Feb 17, 2025, without language restrictions. We included published and unpublished aggregated-level data. The primary outcome was efficacy (measured using validated clinical scales) and the secondary outcome was tolerability (discontinuation due to adverse events). Within-study bias was assessed with the Cochrane Risk of Bias Tool (version 2). We summarised dose–effect associations using a hierarchical Bayesian model with restricted cubic splines. Separate analyses were conducted for children or adolescents (aged <18 years) and adults (aged ≥18 years). The distribution of key effect modifiers was used to examine transitivity of the network. People with lived experience were involved in the conceptualisation and design of the study, and in the interpretation of the findings. The protocol was pre-registered on OSF. Findings: Our 2017 search identified 9948 potential references for inclusion and our Feb 17, 2025 search identified 5148 references. Of these 15 096 references, 8467 were excluded after title and abstract screening, and a further 5862 references were excluded after a full-text read. Of the 767 remaining reports, 164 were included in the systematic review and 113 RCTs (45 in adults and 68 in children and adolescents) were included in the dose–effect network meta-analysis. The 68 RCTs on children and adolescents included 14 138 participants (9981 [70·6%] males and 4157 [29·4%] females) and the 45 RCTs on adults included 11 016 participants (5958 [54·0%] males and 5056 [46·0%] females). Data on ethnicity or race were inconsistently reported across RCTs. We found distinct dose–effect patterns by medication class and age group. In children and adolescents, methylphenidate, amphetamines, and guanfacine showed increasing median efficacy up to 45 mg/day, 25 mg/day and 4 mg/day, respectively, with no evidence of additional benefit at higher doses, although estimates at higher doses were characterised by wide credible intervals. In adults, amphetamines showed a plateau above approximatively 50 mg/day, whereas methylphenidate efficacy increased without evidence of a plateau, possibly due to sparse data. Dose-dependent increases in discontinuation probability due to adverse events were observed for amphetamines (above 25 mg/day for children and 50 mg/day for adults) and methylphenidate (above 50 mg/day for adults, with no clear dose-dependent risk for children). We found no evidence of dose–effect patterns for atomoxetine (in fixed-doses studies) and modafinil. Multiple sensitivity analyses confirmed the robustness of these findings. We found no evidence of intransitivity. Interpretation: Our findings challenge both therapeutic inertia—accepting suboptimal response without further dose titration—and uncritical dose escalation beyond licensed limits, when potential harms outweigh expected benefits. Our findings can inform clinical guidelines and should support shared decision making regarding ADHD medication dosage. 論文原文：Mikail Nourredine, Lucie Jurek, Tasnim Hamza, et al. (2026). Pharmacological interventions for ADHD: a systematic review and dose–effect network meta-analysis. The Lancet / Psychiatry, Volume 13, Issue 6, Pages 485-495. June 2026. https://doi.org/10.1016/S2215-0366(26)00091-X （翻譯兼責任編輯：MARY） （需要英文原文的朋友，請聯繫微信：millerdeng95或iacmsp）
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