抗うつ薬中止症状に関する最大規模のレビュー結果(Results from largest review of its kind on antidepressant withdrawal symptoms)

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2025-07-09 インペリアル・カレッジ・ロンドン(ICL)

抗うつ薬中止症状に関する最大規模のレビュー結果(Results from largest review of its kind on antidepressant withdrawal symptoms)

英インペリアル・カレッジ・ロンドンとキングス・カレッジ・ロンドンなどの研究チームは、抗うつ薬中止による離脱症状を調査した史上最大規模のメタ解析を実施。50の無作為化試験(計17,828人)を分析し、多くの人は重篤な離脱症状を経験しないことが明らかに。主な症状はめまい、吐き気、不安などで、平均1つ追加される程度で臨床的に重大とは言えないレベルだった。うつ病の再発は離脱症状とは無関係とされ、症状の薬剤特異性も確認された。研究は医療現場や政策に新たな指針を提供する。

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抗うつ薬中断症状の発生率と性質 系統的レビューとメタアナリシス Incidence and Nature of Antidepressant Discontinuation Symptoms A Systematic Review and Meta-Analysis

Michail Kalfas, MSc; Dimosthenis Tsapekos, PhD; Matthew Butler, PhD; et al
JAMA Psychiatry  Published:July 9, 2025
DOI:10.1001/jamapsychiatry.2025.1362

Key Points

Question What are the incidence and nature of symptoms following discontinuation of antidepressants?

Findings This systematic review and meta-analysis of 49 randomized clinical trials found that on average, participants who stopped antidepressants experienced 1 more discontinuation symptom compared to those who discontinued placebo or continued antidepressants. The most common symptom in the first 2 weeks following antidepressant discontinuation was dizziness, and discontinuation of antidepressants was not associated with depressive symptoms.

Meaning Individuals who discontinued antidepressants experienced more symptoms compared to those discontinuing placebo or continuing an antidepressant, but the mean number of symptoms was below the cutoff for clinically important discontinuation syndrome.

Abstract

Importance The incidence and nature of discontinuation symptoms following antidepressant cessation remain unclear.

Objective To examine the presence of discontinuation symptoms using standardized scales (eg, Discontinuation-Emergent Signs and Symptoms [DESS]) and the incidence of individual discontinuation symptoms in individuals who stop taking antidepressants.

Data Sources The databases Embase, PsycINFO, Ovid MEDLINE, and Cochrane Library were systematically searched from inception until November 7, 2023.

Study Selection Randomized clinical trials (RCTs) reporting discontinuation symptoms using a standardized scale or individual symptoms (eg, adverse events) following antidepressant cessation were included.

Data Extraction and Synthesis Data extracted were cross-checked by 2 reviewers. Additional unpublished data from 11 RCTs were included. A random-effects meta-analysis was conducted to calculate standardized mean difference between individuals who discontinued an antidepressant vs those who continued an antidepressant or discontinued placebo. A proportion and odds ratio (OR) meta-analysis was performed to assess incidence of individual discontinuation symptoms compared to placebo. Subgroup analyses were conducted to compare different antidepressants. Data analysis was conducted between September 2024 and December 2024.

Main Outcomes and Measures The primary outcomes were incidence and nature of antidepressant discontinuation symptoms measured using standardized or unstandardized scales.

Results A total of 50 studies were included, 49 of which were included in meta-analyses. The 50 studies included 17 828 participants in total, with 66.9% female participants and mean participant age of 44 years. Follow-up was between 1 day and 52 weeks. The DESS meta-analysis indicated increased discontinuation symptoms at 1 week in participants stopping antidepressants (standardized mean difference, 0.31; 95% CI, 0.23-0.39; number of studies [k] = 11; n = 3915 participants) compared to those taking placebo or continuing antidepressants. The effect size was equivalent to 1 more symptom on the DESS. Discontinuation of antidepressants was associated with increased odds of dizziness (OR, 5.52; 95% CI, 3.81-8.01), nausea (OR, 3.16; 95% CI, 2.01-4.96), vertigo (OR, 6.40; 95% CI, 1.20-34.19), and nervousness (OR, 3.15; 95% CI, 1.29-7.64) compared to placebo discontinuation. Dizziness was the most prevalent discontinuation symptom (risk difference, 6.24%). Discontinuation was not associated with depression symptoms, despite being measured in people with major depressive disorder (k = 5).

Conclusions and Relevance This systematic review and meta-analysis indicated that the mean number of discontinuation symptoms at week 1 after stopping antidepressants was below the threshold for clinically significant discontinuation syndrome. Mood worsening was not associated with discontinuation; therefore, later presentation of depression after discontinuation is indicative of depression relapse.

 

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