De Luca Beatrice, Canozzi Andrea, Mosconi Carlotta, Gastaldon Chiara, Papola Davide, Metelli Alessia, Tedeschi Federico, Amaddeo Francesco, Purgato Marianna, Solmi Marco, Barbui Corrado, Vita Giovanni, Ostuzzi Giovanni
WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.
Department of Global Health and Social Medicine, Harvard Medical School, Boston, USA.
Br J Psychiatry. 2025 Apr 4:1-14. doi: 10.1192/bjp.2025.18.
Antidepressants are effective for depression, but most evidence excludes individuals with comorbid physical conditions.
To assess antidepressants' efficacy and tolerability in individuals with depression and comorbid physical conditions.
Systematic review and network meta-analysis of randomised controlled trials (RCTs). Co-primary outcomes were efficacy on depressive symptoms and tolerability (participants dropping out because of adverse events). Bias was assessed with the Cochrane Risk-of-Bias 2 tool and certainty of estimates with the Confidence in Network Meta-Analysis approach. A study protocol was registered in advance (https://osf.io/9cjhe/).
Of the 115 included RCTs, 104 contributed to efficacy (7714 participants) and 82 to tolerability (6083 participants). The mean age was 55.7 years and 51.9% of participants were female. Neurological and cardiocirculatory conditions were the most represented (26.1% and 18.3% of RCTs, respectively). The following antidepressants were more effective than placebo: imipramine, nortriptyline, amitriptyline, desipramine, sertraline, paroxetine, citalopram, fluoxetine, escitalopram, mianserin, mirtazapine and agomelatine, with standardised mean differences ranging from -1.01 (imipramine) to -0.34 (escitalopram). Sertraline and paroxetine were effective for the largest number of ICD-11 disease subgroups (four out of seven). In terms of tolerability, sertraline, imipramine and nortriptyline were less tolerated than placebo, with relative risks ranging from 1.47 (sertraline) to 3.41 (nortriptyline). For both outcomes, certainty of evidence was 'low' or 'very low' for most comparisons.
Antidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit-risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo.
抗抑郁药对抑郁症有效，但大多数证据排除了患有合并身体疾病的个体。
评估抗抑郁药对患有抑郁症和合并身体疾病个体的疗效和耐受性。
对随机对照试验（RCT）进行系统评价和网状Meta分析。共同主要结局是对抑郁症状的疗效和耐受性（因不良事件退出研究的参与者）。使用Cochrane偏倚风险2工具评估偏倚，并采用网状Meta分析的置信度方法评估估计的确定性。研究方案已预先注册（https://osf.io/9cjhe/）。
在纳入的115项RCT中，104项对疗效有贡献（7714名参与者），82项对耐受性有贡献（6083名参与者）。平均年龄为55.7岁，51.9%的参与者为女性。神经和心血管循环系统疾病最为常见（分别占RCT的26.1%和18.3%）。以下抗抑郁药比安慰剂更有效：丙咪嗪、去甲替林、阿米替林、地昔帕明、舍曲林、帕罗西汀、西酞普兰、氟西汀、艾司西酞普兰、米氮平、米安色林和阿戈美拉汀，标准化均数差值范围为-1.01（丙咪嗪）至-0.34（艾司西酞普兰）。舍曲林和帕罗西汀对最多数量的国际疾病分类第11版（ICD-11）疾病亚组有效（七个亚组中的四个）。在耐受性方面，舍曲林、丙咪嗪和去甲替林的耐受性低于安慰剂，相对风险范围为1.47（舍曲林）至3.41（去甲替林）。对于这两个结局，大多数比较的证据确定性为“低”或“非常低”。
抗抑郁药对患有合并身体疾病的个体有效，尽管耐受性是一个相关问题。选择性5-羟色胺再摄取抑制剂（SSRI）具有最佳的效益风险比，使其适合作为一线治疗药物，而三环类药物虽然高效，但耐受性低于SSRI和安慰剂。
