Antidepressants are among the most extensively prescribed psychotropic drugs worldwide. Discontinuation induced withdrawal symptoms have been reported for almost all antidepressants. The incidence of antidepressant withdrawal syndrome (AWS) and other characteristics remain unknown. We searched the PubMed, Embase, PsycINFO, MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials databases from inception to December 31, 2023. Randomized double-blinded trials, longitudinal or cross-sectional studies that reported the incidence and other characteristics of antidepressant withdrawal symptoms were included. The pooled incidence of AWS was calculated by a random effects model. We included 35 studies, of which 2 studies just provided incidence of specific withdrawal symptoms, and 4 studies only described other characteristics. The pooled incidence of AWS from all available studies was 42.9%, from 11 RCTs was 44.4%, in studies in which the treatment duration was mostly 8-12 weeks, which usually appear within 2 weeks, and were generally measured for <4 weeks. The incidence in selective serotonin-norepinephrine reuptake inhibitors was the lowest (29.7%), followed by selective serotonin reuptake inhibitors (45.6%) and tricyclic antidepressants (59.7%), without significant differences (p = 0.221). Treatment duration showed a dose-response to the incidence of AWS (6–12 W: 35.1%, 12–24 W: 42.7%, >24 W: 51.4%). The half-life did not show such a simple dose-dependent relationship. The pooled estimate was robust regardless whether withdrawal symptoms were measured in RCTs or observational studies (including face-to-face and online survey studies). Tapering the dose reduced the incidence of AWS compared with abrupt stoppage (34.5% vs 42.5%), without a significant difference (p = 0.484). Risk factors for withdrawal symptoms included being female, younger, experiencing adverse effects early in treatment, taking higher doses or longer duration of medication, abrupt cessation of drugs, and those with a lower clearance of drugs or with serotonin 1A receptor gene variation. The findings suggest the incidence of AWS are common and some clinical characteristics and risk factors which can help clinicians identify who is at greater risk of experiencing AWS. Discontinuation studies on long-term antidepressant users with long follow-up periods are required in the future.

抗抑郁药是全球处方最广泛的精神药物之一。几乎所有抗抑郁药都报道了停药引起的戒断症状。抗抑郁药戒断综合征 （AWS） 的发生率和其他特征仍然未知。我们检索了从建库到 2023 年 12 月 31 日的 PubMed、Embase、PsycINFO、MEDLINE、CINAHL 和 Cochrane 对照试验中心注册库。纳入了报告抗抑郁药戒断症状发生率和其他特征的随机双盲试验、纵向或横断面研究。AWS 的合并发生率是通过随机效应模型计算的。我们纳入了 35 项研究，其中 2 项研究仅提供了特定戒断症状的发生率，4 项研究仅描述了其他特征。所有可用研究的 AWS 汇总发生率为 42.9%，来自 11 项 RCT 的 44.4%，在这些研究中，治疗持续时间大多为 8-12 周，通常出现在 2 周内，并且通常测量 <4 周。选择性 5-羟色胺-去甲肾上腺素再摄取抑制剂的发生率最低 （29.7%），其次是选择性 5-羟色胺再摄取抑制剂 （45.6%） 和三环类抗抑郁药 （59.7%），无显著差异 （p = 0.221）。治疗持续时间显示对 AWS 发生率的剂量反应 （6-12 W： 35.1%， 12-24 W： 42.7%， >24 W： 51.4%）。半衰期没有显示出如此简单的剂量依赖性关系。无论戒断症状是在 RCT 还是观察性研究 （包括面对面和在线调查研究） 中测量的，汇总估计都是稳健的。与突然停止相比，逐渐减少剂量降低了 AWS 的发生率 （34.5% vs 42.5%），无显著差异 （p = 0.484）。戒断症状的危险因素包括女性、年轻、治疗早期出现不良反应、服用更高剂量或更长时间的药物、突然停药以及药物清除率较低或具有 5-羟色胺 1A 受体基因变异的人。研究结果表明，AWS 的发病率很常见，一些临床特征和风险因素可以帮助临床医生确定谁患 AWS 的风险更大。未来需要对长期随访期的抗抑郁药使用者进行停药研究。