Anxiety disorders are among the most prevalent pediatric behavioral health conditions, affecting roughly 32% of youths prior to adulthood, and associated with impaired functioning that can continue into adulthood and increase in severity.1,2 In this issue of JAMA Pediatrics, Wang et al3 report an updated meta-analysis evaluating the comparative efficacy of cognitive behavioral therapy (CBT) and pharmacotherapy for pediatric anxiety disorders. Results supported the efficacy of CBT, selective serotonin reuptake inhibitors (SSRIs), and their combination; limited support was provided for serotoninnorepinephrine reuptake inhibitors (SNRIs). We briefly review the evidence followed by implementation issues. Resultsofthemeta-analysisindicatethatCBTandSSRIswere each more likely to result in diagnostic remission/treatment response compared with wait list/no treatment and pill placebo, respectively. Combined CBT and medication led to greater improvements in anxiety symptoms compared with CBT alone (2 studies) or medication alone (1 study). Comparison of CBT and SSRIs (2 studies) indicated greater declines in anxiety (symptoms and diagnostic remission) among CBT-treated vs SSRI-treated children.4,5 Some, but less, support was found for SNRIs on a few outcomes in some trials; there was no support for tricyclic medications, benzodiazpines, or buspirone. Adverse events and treatment dropout were more common during pharmacotherapy compared with CBT, although SSRIs and pill placebo did not statistically differ in dropout rates, dropout due to adverse events, or any specific adverse events. With regard to psychiatric adverse events, no suicide deaths or attempts were reported in any study andsuicidalbehaviorappearedtobelessthanindepressionstudies. Behavioral activation, which is sometimes confused with mania, is a psychiatric adverse event especially noteworthy in children younger than 12 years.6 Fromaclinicalperspective,thekeyissuesarehowmanychildren will recover, how much recovery is expected, and how rapidlywillrecoveryoccur.FindingsfromtheChild/AdolescentAnxietyMultimodalStudy,5 thelargestandmostrigorousrandomized clinical trial included in the meta-analysis, provide a relatively clear answer to these questions. Focusing on children ages 7 to 17 years with primary diagnoses of separation anxiety, generalized anxiety, or social phobia, roughly 81% of youths receiving combined SSRI (sertraline) and CBT had shown “much or very much” clinical improvement compared with 55% for SSRI only, 60% for CBT only, and 24% for pill placebo following 12 weeks of treatment. Remission, defined by the loss of all targeted anxiety diagnoses, was observed in 68%, 46%, 46%, and 24% of youths receiving combined SSRI plus CBT, SSRI only, CBT only, and placebotreatment,respectively,at12weeks.7 Childrenreceivingcombined SSRI plus CBT and those receiving SSRI only began to improve earlier, separating from placebo by 4 weeks. At 12 weeks, theCBT-onlyandSSRI-onlygroupsshowedsimilarimprovements with each group improving more relative to pill placebo. Therefore, current evidence indicates that treatments with demonstrated efficacy in the reviewed trials can yield substantial improvements in anxiety symptoms within a relatively brief period. Despite the large number of included studies and novel information presented, the review is constrained by the limitations of the existing evidence base and meta-analytic methods. The meta-analysis and many of the included studies omit analyses of functional outcomes. Anxious children often show school refusal and avoidance behavior that interferes with optimal development. While it is important to know whether anxiety symptoms and global anxiety decline, it is equally and arguably more important to consider treatment effects on school and social functioning. Results varied by informant, with the strongest evidence emerging for clinician reports, compared with parent report, and relatively weak support based solely on child self-report. Only 1 study conducted a head-to-head comparison of CBT, pharmacotherapy, and their combination.5 The meta-analysis was not restricted to randomized clinical trials and included less rigorous nonrandomized comparative studies. The results provide minimal data on which drugs are most effective. Ironically, the best-researched medications are offlabel for childhood anxiety treatment (excluding obsessivecompulsive disorder) with US Food and Drug Administration approval only for duloxetine. Relatively few studies conducted longer-term follow-ups to assess durability of improvements. This important limitation is underscored by Child/Adolescent Anxiety Multimodal Study findings that approximately half of youth receiving gold-standard CBT, SSRI, or CBT plus SSRI treatments experienced diagnostic recurrence within roughly 6 years of initial treatment.8 These data suggest that anxiety disorders may be best viewed as conditions that can be effectively treated in the short term, but characterized by continuing longer-term risk. Future research is needed to evaluate strategies for longerterm monitoring and preventive care after acute treatment. Meta-analytic methods also have their weaknesses, requiring cautious interpretation. By combining results across trials, statistical power is enhanced, improving the ability to Related article Opinion

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小儿焦虑症的药物和认知行为疗法

焦虑症是最普遍的儿科行为健康状况之一，影响了大约 32% 的青少年在成年之前，并且与功能受损相关，这种障碍可以持续到成年并加重。1,2 在本期 JAMA Pediatrics 中，Wang 等人 3报告一项更新的荟萃分析，评估认知行为疗法 (CBT) 和药物疗法对儿科焦虑症的比较疗效。结果支持 CBT、选择性 5-羟色胺再摄取抑制剂 (SSRIs) 及其组合的疗效；对 5-羟色胺去甲肾上腺素再摄取抑制剂 (SNRI) 的支持有限。我们简要回顾了证据，然后是实施问题。荟萃分析的结果表明，与等待名单/未治疗和安慰剂安慰剂相比，CBT 和 SSRIs 各自更可能导致诊断缓解/治疗反应。与单独的 CBT（2 项研究）或单独的药物治疗（1 项研究）相比，CBT 和药物联合治疗可更大程度地改善焦虑症状。CBT 和 SSRIs 的比较（2 项研究）表明，接受 CBT 治疗的儿童与接受 SSRI 治疗的儿童的焦虑（症状和诊断缓解）下降幅度更大。 4,5 在一些试验中发现一些但较少支持 SNRIs 对一些结果的支持; 不支持三环类药物、苯二氮卓类药物或丁螺环酮。与 CBT 相比，药物治疗期间的不良事件和治疗退出更常见，尽管 SSRI 和安慰剂在退出率、因不良事件导致的退出、或任何特定的不良事件。关于精神方面的不良事件，在任何研究中都没有报告自杀死亡或企图自杀，自杀行为似乎比抑郁症研究更糟糕。行为激活有时与躁狂症相混淆，是一种在 12 岁以下儿童中尤其值得注意的精神不良事件。6 从临床角度来看，关键问题是有多少儿童能够康复、预计康复的程度以及恢复的速度。儿童/青少年焦虑症多模式研究的结果，5 包括最严格的大型随机临床试验在荟萃分析中，对这些问题提供了比较明确的答案。专注于主要诊断为分离焦虑、广泛性焦虑或社交恐惧症的 7 至 17 岁儿童，在接受 SSRI（舍曲林）和 CBT 联合治疗的青少年中，大约 81% 的青少年在治疗 12 周后表现出“很多或非常多”的临床改善，而仅 SSRI 的这一比例为 55%，仅 CBT 的比例为 60%，安慰剂组的比例为 24%。在接受联合 SSRI 加 CBT、仅 SSRI、仅 CBT 和安慰剂治疗的青少年中，分别有 68%、46%、46% 和 24% 的青少年在 12 周时观察到缓解，即所有针对性的焦虑诊断均消失。7 儿童接受联合治疗SSRI 加 CBT 和那些接受 SSRI 的人开始改善更早，与安慰剂分开 4 周。在第 12 周时，仅 CBT 组和仅 SSRI 组显示出类似的改善，每组相对于安慰剂安慰剂的改善更多。所以，目前的证据表明，在审查的试验中证明有效的治疗可以在相对较短的时间内显着改善焦虑症状。尽管有大量纳入研究和新信息，但该评价受到现有证据基础和元分析方法的限制。荟萃分析和许多纳入的研究省略了对功能结果的分析。焦虑的孩子经常表现出阻碍最佳发展的学校拒绝和回避行为。虽然了解焦虑症状和整体焦虑是否下降很重要，但考虑治疗对学校和社会功能的影响同样重要，而且可以说更重要。结果因线人而异，临床医生报告中出现了最有力的证据，与家长报告相比，仅基于儿童自我报告的支持相对较弱。只有 1 项研究对 CBT、药物疗法及其组合进行了头对头比较。5 荟萃分析不限于随机临床试验，还包括不太严格的非随机比较研究。结果提供了关于哪些药物最有效的最少数据。具有讽刺意味的是，美国食品和药物管理局仅批准度洛西汀治疗儿童焦虑症（不包括强迫症）的最佳研究药物是超标的。相对较少的研究进行了长期随访以评估改进的持久性。儿童/青少年焦虑多模式研究结果强调了这一重要限制，大约一半的青少年接受金标准 CBT、SSRI、或 CBT 加 SSRI 治疗在初始治疗后大约 6 年内经历了诊断性复发。8 这些数据表明，焦虑症最好被视为可以在短期内得到有效治疗的疾病，但其特征是持续的长期风险。未来的研究需要评估急性治疗后长期监测和预防性护理的策略。元分析方法也有其弱点，需要谨慎解释。通过合并试验结果，增强了统计能力，提高了对相关文章意见的能力 但特点是持续的长期风险。未来的研究需要评估急性治疗后长期监测和预防性护理的策略。元分析方法也有其弱点，需要谨慎解释。通过合并试验结果，增强了统计能力，提高了对相关文章意见的能力 但其特点是持续的长期风险。未来的研究需要评估急性治疗后长期监测和预防性护理的策略。元分析方法也有其弱点，需要谨慎解释。通过合并试验结果，增强了统计能力，提高了对相关文章意见的能力