2026-11-11 京都大学
京都大学などの国際研究グループは、成人のうつ病患者を対象とした115件のランダム化比較試験、計30,428人のデータを用いて、抗うつ薬の長期的な有効性と忍容性を比較評価した。ネットワークメタアナリシスにより、12週間を超える長期投与における症状改善の維持率と治療継続性を検証した。その結果、エスシタロプラム、デュロキセチン、アゴメラチンの3剤は、フルオキセチンと比較して有意に高い持続的反応率を示した。さらに、エスシタロプラムとデュロキセチンは、全原因による治療中断率も低く、長期的な有効性と忍容性の両面で優れていることが確認された。本研究は、抗うつ薬の選択において、治療初期の症状改善だけでなく、その効果を長期間維持できるかという観点の重要性を示している。うつ病の再発予防や長期治療を考慮した薬剤選択に科学的根拠を提供し、患者と医師が共同で治療方針を決定する共有意思決定（Shared Decision Making）の促進に貢献すると期待される。
抗うつ薬の長期の有効性・忍容性の比較（田近亜蘭作成 イラストAC 、Gemini 3.6 Flash使用）
＜関連情報＞
- https://www.kyoto-u.ac.jp/ja/research-news/2026-11-11
- https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(26)00326-3/abstract
大うつ病性障害の長期治療における抗うつ薬の比較有効性と許容性：システマティックレビューとネットワークメタアナリシス Comparative efficacy and acceptability of antidepressants in the long-term treatment of major depressive disorder: a systematic review and network meta-analysis
Paul C F van Haaren, MD MSc ∙ Jakob M van Gaalen, MD MSc ∙ Edoardo G Ostinelli, MD PhD ∙ Kiyomi Shinohara, MD PhD ∙ Aran Tajika, MD PhD ∙ Rosario Aronica, MD ∙ et al.
The Lancet Psychiatry Published: November 10, 2026
DOI:https://doi.org/10.1016/S2215-0366(26)00326-3
Summary
Major depressive disorder carries high risks of relapse and chronicity, necessitating treatments that achieve and maintain response (sustained response). This study aimed to compare antidepressants on their ability to achieve sustained response, and on acceptability, by synthesising data from randomised controlled trials.
For this systematic review and network meta-analysis, we searched the Cochrane Register, AMED, CINAHL, Embase, LILACS, MEDLINE, MEDLINE In-Progress, PsycINFO, the UK National Research Register, and regulatory agency websites from inception to March 27, 2026. We included double-blind randomised controlled trials that compared any of 21 antidepressants head-to-head or with placebo for long-term treatment (>12 weeks) of adult unipolar major depressive disorder. We included enrichment, non-enrichment, continuation, and continuation–extension designs, and extracted study-level data. We could not derive the sex or gender distribution of participants other than female and did not extract data on race or ethnicity. Primary outcomes were efficacy (sustained response rate) and acceptability (all-cause discontinuation). We synthesised data in random-effects pairwise and network meta-analyses to estimate pooled odds ratios (ORs), using fluoxetine as a reference in the ranked forest plots. The primary analysis included head-to-head continuation and continuation–extension design studies. Enrichment design studies were incorporated in the analysis using a chain-of-evidence approach. Risk-of-bias assessment was done using the Cochrane Risk of Bias 2 tool. No people with lived experience were involved in the design, conduct, or interpretation of this study.
From 54 231 records, 115 studies (30 428 participants; mean age 45·3 years [SD 8·5], 20 066 [66%] female) were included. In head-to-head continuation and continuation–extension design studies (35 studies; n=9888), sustained response differed across antidepressants. Escitalopram (OR 1·62, 95% CI 1·21–2·18), duloxetine (OR 1·57, 1·08–2·26), and agomelatine (OR 1·40, 1·06–1·85) showed higher sustained response rates than fluoxetine. Bupropion and reboxetine showed lower sustained response rates against four other antidepressants in the league table of pairwise comparisons. Escitalopram (OR 0·60, 0·43–0·83) and duloxetine (OR 0·64, 0·44–0·95) demonstrated lower all-cause discontinuation compared with fluoxetine, while reboxetine and milnacipran showed higher all-cause discontinuation against six and four other antidepressants, respectively, in the league table of pairwise comparisons. Sensitivity analyses incorporating enrichment-design studies corroborated these results. However, the certainty of evidence of the network meta-analysis results and the risk of bias in the included studies (19 [54%] of 35 had high risk of bias) might limit the reliability of the current findings.
Antidepressants can differ in their efficacy for achieving sustained response and in their acceptability. These findings can inform the shared decision making for patients, prescribers, and carers in real-world practice. However, more head-to-head comparative studies are needed to provide reliable information about long-term effects of all licensed antidepressants.
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