Supplementary Material for: Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review

Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: ‘withdrawal symptoms' OR ‘withdrawal syndrome' OR ‘discontinuation syndrome' OR ‘discontinuation symptoms', AND ‘SSRI' OR ‘serotonin' OR ‘antidepressant' OR ‘paroxetine' OR ‘fluoxetine' OR ‘sertraline' OR ‘fluvoxamine' OR ‘citalopram' OR ‘escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome'.背景：选择性5-羟色胺再摄取抑制剂（Selective serotonin reuptake inhibitors, SSRI）在临床实践中应用广泛。这类药物与多种症状相关，但其临床意义尚未被充分认知。 方法：本研究遵循PRISMA指南开展系统文献综述。检索标题、摘要及主题词时采用以下组合关键词：「撤药症状」或「撤药综合征」或「停药综合征」或「停药症状」，且「SSRI」或「5-羟色胺」或「抗抑郁药」或「帕罗西汀」或「氟西汀」或「舍曲林」或「氟伏沙明」或「西酞普兰」或「艾司西酞普兰」。电子文献数据库检索涵盖CINAHL、Cochrane Library、PubMed及Web of Science，检索时限为各数据库建库至2014年7月。 结果：本研究共纳入15项随机对照试验、4项开放试验、4项回顾性研究及38个病例报告。该综合征的患病率存在差异，且由于众多研究未对病例进行识别，导致其患病率估算存在困难。症状通常在停药后数天内出现，持续数周，即使采用逐渐减量给药方案也可能发生。不过也存在多种变异情况，包括迟发性发作或症状持续时间更长。此类症状易被误判为疾病复发的前兆。 结论：临床医师应将SSRI与苯二氮䓬类、巴比妥类及其他精神药物一同纳入停药后可能诱发撤药症状的药物清单。当前使用的「停药综合征」这一术语低估了SSRI所致的潜在风险，应替换为「撤药综合征」。