Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
JAMA Psychiatry. 2023 Dec 1;80(12):1196-1207. doi: 10.1001/jamapsychiatry.2023.2983.
IMPORTANCE: Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent. OBJECTIVE: To perform an umbrella systematic review of the meta-analytic evidence and meta-analysis of the efficacy and safety of antidepressant use in populations with medical diseases and comorbid depression. DATA SOURCES: PubMed and EMBASE were searched from inception until March 31, 2023, for systematic reviews with or without meta-analyses of randomized clinical trials (RCTs) examining the efficacy and safety of antidepressants for treatment or prevention of comorbid depression in any medical disease. STUDY SELECTION: Meta-analyses of placebo- or active-controlled RCTs studying antidepressants for depression in individuals with medical diseases. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment using A Measurement Tool for the Assessment of Multiple Systematic Reviews (AMSTAR-2 and AMSTAR-Content) were performed by pairs of independent reviewers following PRISMA guidelines. When several meta-analyses studied the same medical disease, the largest meta-analysis was included. Random-effects meta-analyses pooled data on the primary outcome (efficacy), key secondary outcomes (acceptability and tolerability), and additional secondary outcomes (response and remission). MAIN OUTCOMES AND MEASURES: Antidepressant efficacy presented as standardized mean differences (SMDs) and tolerability (discontinuation for adverse effects) and acceptability (all-cause discontinuation) presented as risk ratios (RRs). RESULTS: Of 6587 references, 176 systematic reviews were identified in 43 medical diseases. Altogether, 52 meta-analyses in 27 medical diseases were included in the evidence synthesis (mean [SD] AMSTAR-2 quality score, 9.3 [3.1], with a maximum possible of 16; mean [SD] AMSTAR-Content score, 2.4 [1.9], with a maximum possible of 9). Across medical diseases (23 meta-analyses), antidepressants improved depression vs placebo (SMD, 0.42 [95% CI, 0.30-0.54]; I2 = 76.5%), with the largest SMDs for myocardial infarction (SMD, 1.38 [95% CI, 0.82-1.93]), functional chest pain (SMD, 0.87 [95% CI, 0.08-1.67]), and coronary artery disease (SMD, 0.83 [95% CI, 0.32-1.33]) and the smallest for low back pain (SMD, 0.06 [95% CI, 0.17-0.39]) and traumatic brain injury (SMD, 0.08 [95% CI, -0.28 to 0.45]). Antidepressants showed worse acceptability (24 meta-analyses; RR, 1.17 [95% CI, 1.02-1.32]) and tolerability (18 meta-analyses; RR, 1.39 [95% CI, 1.13-1.64]) compared with placebo. Antidepressants led to higher rates of response (8 meta-analyses; RR, 1.54 [95% CI, 1.14-1.94]) and remission (6 meta-analyses; RR, 1.43 [95% CI, 1.25-1.61]) than placebo. Antidepressants more likely prevented depression than placebo (7 meta-analyses; RR, 0.43 [95% CI, 0.33-0.53]). CONCLUSIONS AND RELEVANCE: The results of this umbrella systematic review of meta-analyses found that antidepressants are effective and safe in treating and preventing depression in patients with comorbid medical disease. However, few large, high-quality RCTs exist in most medical diseases.
重要性：每三到六位患有内科疾病的患者会接受抗抑郁药物治疗，但监管试验通常排除共病性内科疾病。抗抑郁药物的荟萃分析显示出小到中等的效应大小，但在共病患病率较高的临床环境中，其普遍性尚不清楚。 目的：对有内科疾病和共病抑郁症的人群中使用抗抑郁药物的疗效和安全性的荟萃分析证据进行伞式系统综述和荟萃分析。 数据来源：从创建到 2023 年 3 月 31 日，在 PubMed 和 EMBASE 上搜索了系统评价，无论是否进行了荟萃分析，这些系统评价都检查了在任何内科疾病中使用抗抑郁药物治疗或预防共病抑郁症的疗效和安全性的随机对照试验（RCT）。 研究选择：对有内科疾病且患有抑郁症的患者进行安慰剂或活性对照 RCT 的荟萃分析。 数据提取和综合：使用评估多个系统评价的测量工具（AMSTAR-2 和 AMSTAR-Content），由两名独立审查员按照 PRISMA 指南进行数据提取和质量评估。当几项荟萃分析研究了相同的内科疾病时，纳入了最大的荟萃分析。使用随机效应荟萃分析汇总了主要结局（疗效）、关键次要结局（可接受性和耐受性）和额外的次要结局（反应和缓解）的数据。 主要结果和措施：抗抑郁药物的疗效表现为标准化均数差异（SMD），耐受性（因不良反应停药）和可接受性（所有原因停药）表现为风险比（RR）。 结果：在 6587 条参考文献中，共确定了 43 种内科疾病的 176 项系统评价。总共纳入了 27 种内科疾病的 52 项荟萃分析（平均[标准差] AMSTAR-2 质量评分，9.3[3.1]，最大可能为 16；平均[标准差] AMSTAR-Content 评分，2.4[1.9]，最大可能为 9）。在所有内科疾病中（23 项荟萃分析），与安慰剂相比，抗抑郁药物改善了抑郁症（SMD，0.42[95%CI，0.30-0.54]；I2=76.5%），其中最大的 SMD 见于心肌梗死（SMD，1.38[95%CI，0.82-1.93]）、功能性胸痛（SMD，0.87[95%CI，0.08-1.67]）和冠状动脉疾病（SMD，0.83[95%CI，0.32-1.33]），而最小的 SMD 见于下腰痛（SMD，0.06[95%CI，0.17-0.39]）和创伤性脑损伤（SMD，0.08[95%CI，-0.28 至 0.45]）。与安慰剂相比，抗抑郁药物的可接受性（24 项荟萃分析；RR，1.17[95%CI，1.02-1.32]）和耐受性（18 项荟萃分析；RR，1.39[95%CI，1.13-1.64]）更差。与安慰剂相比，抗抑郁药物导致更高的反应率（8 项荟萃分析；RR，1.54[95%CI，1.14-1.94]）和缓解率（6 项荟萃分析；RR，1.43[95%CI，1.25-1.61]）。与安慰剂相比，抗抑郁药物更有可能预防抑郁症（7 项荟萃分析；RR，0.43[95%CI，0.33-0.53]）。 结论和相关性：本荟萃分析伞式系统综述的结果发现，抗抑郁药物在治疗和预防有共病内科疾病的患者的抑郁症方面是有效和安全的。然而，大多数内科疾病中都存在很少的高质量 RCT。
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