Zhang Mi-Mi, Tan Xuan, Zheng Yong-Bo, Zeng Na, Li Zhe, Horowitz Mark Abie, Feng Xue-Zhu, Wang Ke, Li Zi-Yi, Zhu Wei-Li, Zhou Xinyu, Xie Peng, Zhang Xiujun, Wang Yumei, Shi Jie, Bao Yan-Ping, Lu Lin, Li Su-Xia
National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing, China.
Department of Psychiatry, Xijing Hospital, Air Force Medical University, Xi'an, China.
Mol Psychiatry. 2025 May;30(5):1758-1769. doi: 10.1038/s41380-024-02782-4. Epub 2024 Oct 11.
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.
抗抑郁药是全球范围内处方最为广泛的精神类药物之一。几乎所有抗抑郁药都有停药引发戒断症状的报道。抗抑郁药戒断综合征（AWS）的发生率及其他特征尚不清楚。我们检索了PubMed、Embase、PsycINFO、MEDLINE、CINAHL以及Cochrane对照试验中央注册库数据库，检索时间从建库至2023年12月31日。纳入报告了抗抑郁药戒断症状发生率及其他特征的随机双盲试验、纵向或横断面研究。采用随机效应模型计算AWS的合并发生率。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。所有可用研究中AWS的合并发生率为42.9%，11项随机对照试验中的发生率为44.4%，在治疗时长大多为8至12周的研究中，这些症状通常在2周内出现，且一般测量时长小于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%），差异无统计学意义（p = 0.221）。治疗时长对AWS的发生率呈剂量反应关系（6至12周：35.1%，12至24周：42.7%，超过24周：51.4%）。半衰期未显示出如此简单的剂量依赖关系。无论戒断症状是在随机对照试验还是观察性研究（包括面对面和在线调查研究）中测量，合并估计值都很稳健。与突然停药相比，逐渐减少剂量可降低AWS的发生率（34.5%对42.5%），差异无统计学意义（p = 0.484）。戒断症状的风险因素包括女性、年轻、在治疗早期出现不良反应、服用较高剂量或较长疗程的药物、突然停药，以及药物清除率较低或有5-羟色胺1A受体基因变异的患者。研究结果表明，AWS的发生率很常见，还有一些临床特征和风险因素可帮助临床医生识别哪些人发生AWS的风险更高。未来需要针对长期使用抗抑郁药且随访期长的患者开展停药研究。
