Data_Sheet_1_Risk of Suicidal Behaviors and Antidepressant Exposure Among Children and Adolescents: A Meta-Analysis of Observational Studies.docx

ObjectivesAlthough several studies have reviewed the suicidal risk of antidepressants, the conclusions remain inconsistent. We, therefore, performed a meta-analysis of observational studies to address the association between exposure to antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and the risk of suicide and suicide attempt in children and adolescents.
MethodsMEDLINE and Embase were searched from January 1990 to April 2021. Seventeen cohort and case-control studies were identified that reported suicide or suicide attempt in children and young adults (aged 5–25 years) who were exposed to any antidepressants. We extracted the estimates and corresponding 95% confidence intervals (CIs) from each publication.
ResultsThe results showed that antidepressant exposure significantly increased the risk of suicide and suicide attempt when compared with no antidepressant usage among children and adolescents. The pooled relative risk (RR) was 1.38 (95% CI: 1.16–1.64; I2 = 83.1%). Among the antidepressants, SSRI use was associated with an increased risk of suicide and suicide attempt, and the pooled RR was 1.28 (95% CI: 1.09–1.51; I2 = 68.8%). In subgroup analysis, the attempted suicidal risk of antidepressant and SSRI was significantly increased (RR = 1.35, 95% CI: 1.13–1.61; I2 = 86.2% for all antidepressants; and RR = 1.26, 95% CI: 1.06–1.48; I2 = 73.8% for SSRIs), while the completed suicidal risk of antidepressant and SSRI was not statistically significant (RR = 2.32, 95% CI: 0.82–6.53; I2 = 6.28% for all antidepressants; and RR = 1.88, 95% CI: 0.74–4.79; I2 = 52.0% for SSRIs). In addition, the risk of suicide and suicide attempt between SSRIs and other antidepressants was similar (RR 1.13, 95% CI: 0.87–1.46, I2 = 32.4%).
ConclusionThe main findings of this meta-analysis provide some evidence that antidepressant exposure seems to have an increased suicidal risk among children and young adults. Since untreated depression remains one of the largest risk factors for suicide and the efficacy of antidepressants is proven, clinicians should evaluate carefully their patients and be cautious with patients at risk to have treatment emergence or worsening of suicidal ideation (TESI/TWOSI) when prescribing antidepressants to children and young patients.

研究背景与目的：尽管已有多项研究对抗抑郁药的自杀风险进行了综述，但相关结论仍存在分歧。因此，我们开展了一项观察性研究的元分析（meta-analysis），以探讨抗抑郁药暴露——尤其是选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors, SSRIs）——与儿童及青少年自杀及自杀未遂风险之间的关联。
研究方法：本研究检索了1990年1月至2021年4月期间MEDLINE与Embase数据库中的文献。最终纳入17项队列研究与病例对照研究，这些研究均报告了暴露于任意抗抑郁药的儿童与青年（年龄5~25岁）的自杀或自杀未遂情况。我们从每篇文献中提取了效应估计值及其对应的95%置信区间（confidence intervals, CIs）。
研究结果：结果显示，与未使用抗抑郁药的儿童及青少年相比，抗抑郁药暴露可显著升高自杀及自杀未遂风险。合并相对风险（relative risk, RR）为1.38（95%CI：1.16~1.64；I²=83.1%）。在各类抗抑郁药中，选择性5-羟色胺再摄取抑制剂的使用与自杀及自杀未遂风险升高相关，合并相对风险为1.28（95%CI：1.09~1.51；I²=68.8%）。亚组分析结果显示，抗抑郁药与选择性5-羟色胺再摄取抑制剂的自杀未遂风险均显著升高（所有抗抑郁药：RR=1.35，95%CI：1.13~1.61；I²=86.2%；选择性5-羟色胺再摄取抑制剂：RR=1.26，95%CI：1.06~1.48；I²=73.8%），而二者的自杀既遂风险均无统计学显著性（所有抗抑郁药：RR=2.32，95%CI：0.82~6.53；I²=6.28%；选择性5-羟色胺再摄取抑制剂：RR=1.88，95%CI：0.74~4.79；I²=52.0%）。此外，选择性5-羟色胺再摄取抑制剂与其他抗抑郁药之间的自杀及自杀未遂风险无显著差异（RR=1.13，95%CI：0.87~1.46，I²=32.4%）。
研究结论：本项元分析的主要发现提供了一定证据，表明抗抑郁药暴露似乎会升高儿童及青年群体的自杀风险。鉴于未接受治疗的抑郁症仍是自杀的最大风险因素之一，且抗抑郁药的疗效已得到证实，临床医师在为儿童及青年患者开具抗抑郁药处方时，应仔细评估患者情况，并警惕治疗过程中出现的治疗相关自杀意念新发或恶化（treatment emergence or worsening of suicidal ideation, TESI/TWOSI）。