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Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis
The Lancet Psychiatry ( IF 30.8 ) Pub Date : 2024-06-05 , DOI: 10.1016/s2215-0366(24)00133-0
Jonathan Henssler 1 , Yannick Schmidt 2 , Urszula Schmidt 2 , Guido Schwarzer 3 , Tom Bschor 4 , Christopher Baethge 2
Affiliation  

Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature. We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables. From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6–64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27–0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14–0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04–0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014–0·057) compared with 0·006 (0·002–0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial. Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm. None.

中文翻译:


抗抑郁药停药症状的发生率:系统评价和荟萃分析



抗抑郁药停药症状正成为临床实践中越来越重要的一部分,但抗抑郁药停药症状的发生率尚未量化。抗抑郁药停药症状发生率的估计可以为患者和临床医生停止治疗提供信息,并为抗抑郁药治疗的研究人员提供有用的信息。我们旨在评估已发表文献中停用抗抑郁药和安慰剂的患者抗抑郁药停药症状的发生率。我们从数据库建库到 2022 年 10 月 13 日系统检索了 Medline、EMBASE 和 CENTRAL,以查找随机对照试验 (RCT)、其他对照试验和评估抗抑郁药停药症状发生率的观察性研究。要纳入,研究必须调查患有任何精神、行为或神经发育障碍的参与者停止或逐渐减少已确定的抗抑郁药(不包括抗精神病药、锂或甲状腺素)或安慰剂的情况。我们排除了针对新生儿的研究,以及那些使用抗抑郁药治疗身体状况的研究,例如器质性疾病引起的疼痛综合征。在研究选择、汇总资料提取和偏倚风险评估后,将数据合并到随机效应meta分析中。主要结局是停用抗抑郁药或安慰剂后抗抑郁药停药症状的发生率。我们还分析了严重停药症状的发生率。敏感性和 meta 回归分析测试了一系列方法学变量。 从筛选的 6095 篇文章中,选择了 79 项研究(44 项随机对照试验和 35 项观察性研究),涵盖 21 002 名患者(72% 为女性,28% 为男性,平均年龄 45 岁 [范围 19·6–64·5])。关于种族的数据没有得到一致的报告。16 532 名患者停用抗抑郁药,4470 名患者停用安慰剂。停用抗抑郁药后,62 个研究组中至少一种抗抑郁药停药症状的发生率为 0·31 (95% CI 0·27–0·35),停用安慰剂后 22 个研究组中为 0·17 (0·14–0·21)。在纳入的 RCT 的抗抑郁药组和安慰剂组之间,发生率的总差异为 0·08 [0·04–0·12]。停用抗抑郁药后严重抗抑郁药停药症状的发生率为 0·028 (0·014–0·057),而停用安慰剂后为 0·006 (0·002–0·013)。去甲文拉法辛、文拉法辛、丙咪嗪和艾司西酞普兰与较高的停药症状频率相关,丙咪嗪、帕罗西汀和去甲文拉法辛或文拉法辛与更严重的症状相关。结果的异质性很大。考虑到非特异性效应,如安慰剂组所示,抗抑郁药停药症状的发生率约为 15%,影响了 6 至 7 名停药患者中的 1 名。亚组分析和异质性数据指出了诊断、药物或试验相关特征未考虑的因素,并且可能表明研究者、患者或两者的主观因素。 在解释结果时,需要考虑残留或重新出现的精神病理学,但我们的研究结果可以告知临床医生和患者抗抑郁药停药症状的可能程度,而不会引起过度的恐慌。没有。
更新日期:2024-06-05
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