Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jul 13:109:110266. doi: 10.1016/j.pnpbp.2021.110266. Epub 2021 Feb 5.


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.

Keywords: Antidepressants; Gastrointestinal side effects; Major depressive disorder; Neuropsychopharmacology; Personalised medicine; Tolerability.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antidepressive Agents / adverse effects*
  • Constipation / chemically induced*
  • Depressive Disorder, Major / drug therapy*
  • Diarrhea / chemically induced*
  • Humans
  • Nausea / chemically induced*
  • Vomiting / chemically induced*


  • Antidepressive Agents