Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment discontinuation. The aim of this meta-analysis is to provide quantitative measures on short-term rates of gastrointestinal SEs in MDD patients treated with second-generation antidepressants.

An electronic search of the literature was conducted by using MEDLINE, ISI Web of Science – Web of Science Core Collection, and Cochrane Library databases. Eligible studies had to focus on the use of at least one of 15 antidepressants commonly used in MDD (i.e., agomelatine, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, and vortioxetine) and report data on treatment-emergent gastrointestinal SEs (i.e. nausea/vomiting, diarrhoea, constipation, abdominal pain, dyspepsia, anorexia, increased appetite and dry mouth) within 12 weeks of treatment.

Overall, 304 studies were included in the meta-analyses. All the considered antidepressants showed higher rates of gastrointestinal SEs than placebo. Escitalopram and sertraline were shown to be the least tolerated antidepressants on the gastrointestinal tract, being associated with all the considered SEs with the exception of constipation and increased appetite, while mirtazapine was shown to be the antidepressant with fewer side effects on the gut, being only associated with increased appetite.

In conclusion, commonly used antidepressants showed different profiles of gastrointestinal SEs, possibly related to their mechanisms of action. The specific tolerability profile of each compound should be considered by clinicians when prescribing antidepressants in order to improve adherence to treatment and increase positive outcomes in patients with MDD.

患有重度抑郁症 (MDD) 的患者在服用抗抑郁药时经常观察到胃肠道副作用 (SE)，并可能导致治疗中断。这项荟萃分析的目的是提供对使用第二代抗抑郁药治疗的 MDD 患者胃肠道 SEs 短期发生率的定量测量。

使用 MEDLINE、ISI Web of Science – Web of Science 核心合集和 Cochrane 图书馆数据库对文献进行电子检索。符合条件的研究必须集中在 MDD 常用的 15 种抗抑郁药中的至少一种（即阿戈美拉汀、安非他酮、西酞普兰、去甲文拉法辛、度洛西汀、依他普仑、氟西汀、氟伏沙明、左旋米那普仑、米氮平、帕罗西汀、瑞波西汀、舍曲林、文拉法辛、和 vortioxetine），并报告治疗后 12 周内出现的胃肠道 SE（即恶心/呕吐、腹泻、便秘、腹痛、消化不良、厌食、食欲增加和口干）的数据。

总体而言，荟萃分析纳入了 304 项研究。所有考虑的抗抑郁药都显示出比安慰剂更高的胃肠道 SE 发生率。依他普仑和舍曲林被证明是胃肠道耐受性最低的抗抑郁药，除了便秘和食欲增加外，与所有考虑的 SE 相关，而米氮平被证明是对肠道副作用较少的抗抑郁药，仅与食欲增加有关。

总之，常用的抗抑郁药表现出不同的胃肠道 SEs 特征，可能与其作用机制有关。临床医生在开抗抑郁药时应考虑每种化合物的特定耐受性，以提高 MDD 患者对治疗的依从性并增加积极结果。