Antidepressants’ effects are established in randomised controlled trials (RCTs), but not in the real world.

To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.

We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnosis of depression, exposed to licensed antidepressants in the UK. We assessed all-cause dropouts (acceptability), dropouts for adverse events (tolerability), occurrence of at least one adverse event (safety), and response and remission on the Patient Health Questionnaire (PHQ)-9 (effectiveness) at 2 and 12 months. Logistic regressions were used to compute adjusted-odds ratio (aOR) with 99% CIs, assessing the associations between exposure to each antidepressant against fluoxetine (comparator) and outcomes of interest. We compared estimates from the real world with RCTs using ratio-of-odds ratio (ROR) with 95% CI.

A total of 673 177 depressed people were studied: females 57.1%, mean age 42.8 (s.d. 17.7) years, mean baseline PHQ-9 17.1 (s.d. 5.0) (moderately severe depression). At 2 months, antidepressant acceptability was 61.4%, tolerability 94.4%, safety 54.5%, PHQ-9 decreased to 12.3 (s.d. 6.5). At 12 months, acceptability was 12.3%, tolerability 87.5%, safety 28.8%, PHQ-9 12.9 (s.d. 6.8). In the short and long term, tricyclics, mirtazapine and trazodone were worse than fluoxetine for most outcomes; citalopram had better acceptability than fluoxetine (aOR 0.95; 99% CI 0.92, 0.97), sertraline had lower tolerability (aOR 1.12; 99% CI 1.06, 1.18), and both citalopram and sertraline had lower safety (aOR 1.17 and 1.25, respectively). In the long term, citalopram had better acceptability (aOR 0.78; 99% CI 0.76, 0.81) and effectiveness (aOR 1.12 for both response and remission), but worse tolerability (aOR 1.09; 99% CI 1.06, 1.13) and safety (aOR 1.12; 99% CI 1.08, 1.16). Observational and randomised data were similar for citalopram and sertraline, while there was some difference for drugs less prescribed in the real world.

Antidepressants showed low acceptability, moderate-to-high tolerability and safety, and small-to-moderate effectiveness in the real world. Real-world and RCT estimates showed similar findings only when the analyses were carried out using large datasets; otherwise, the results diverged.

抗抑郁药的作用是在随机对照试验 （RCT） 中确定的，但在现实世界中不是。

研究抗抑郁药对抑郁症的真实世界比较效果，并将其与 RCT 进行比较。

我们进行了一项基于 QResearch 数据库的队列研究。我们纳入了在英国新诊断为抑郁症、暴露于许可抗抑郁药的人。我们评估了 2 个月和 12 个月时全因退出 （可接受性）、不良事件退出 （耐受性）、至少一种不良事件的发生 （安全性） 以及患者健康问卷 （PHQ）-9 （有效性） 的反应和缓解。使用 Logistic 回归计算具有 99% CI 的调整比值比 （aOR），评估暴露于每种抗抑郁药与氟西汀（对照）之间的关联与感兴趣的结局之间的关联。我们使用比值比 （ROR） 和 95% CI 将真实世界的估计值与 RCT 进行了比较。

共研究了 673 177 名抑郁症患者：女性 57.1%，平均年龄 42.8 （s.d. 17.7） 岁，平均基线 PHQ-9 17.1 （s.d. 5.0） （中度重度抑郁症）。2 个月时，抗抑郁药可接受性为 61.4%，耐受性为 94.4%，安全性为 54.5%，PHQ-9 降至 12.3 （s.d. 6.5）。12 个月时，可接受性为 12.3%，耐受性为 87.5%，安全性为 28.8%，PHQ-9 为 12.9 （s.d. 6.8）。在短期和长期内，三环类药物、米氮平和曲唑酮的大多数结局比氟西汀差;西酞普兰的可接受性优于氟西汀（aOR 0.95;99% CI 0.92,0.97），舍曲林的耐受性较低（aOR 1.12;99% CI 1.06,1.18），西酞普兰和舍曲林的安全性较低（aOR 分别为 1.17 和 1.25）。从长期来看，西酞普兰的可接受性 （aOR 0.78;99% CI 0.76， 0.81） 和有效性 （反应和缓解的 aOR 1.12） 较好，但耐受性 （aOR 1.09;99% CI 1.06， 1.13） 和安全性较差 （aOR 1.12;99% CI 1.08， 1.16）。西酞普兰和舍曲林的观察和随机数据相似，而现实世界中处方较少的药物存在一些差异。

抗抑郁药在现实世界中显示出低可接受性、中度至高度耐受性和安全性，以及小到中等的有效性。真实世界和 RCT 估计仅在使用大型数据集进行分析时才显示出相似的结果;否则，结果会有所不同。