Objectives: This systematic review aims to analyze the safety of mirtazapine in patients aged 60 years or older, as well as its side effects in this population.

Methods: A systematic literature search was performed based on the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. Searches were conducted in the Embase, LILACS, PsycINFO, PubMed, Scopus, and Web of Science for articles published in any language using the terms Mirtazapine AND (pharmacovigilance OR ‘side effect*’ OR ‘adverse reaction*’ OR ‘adverse event*’ OR safety). This review was registered in PROSPERO: CRD42023492249.

Results: Seventy-two papers met the inclusion criteria. A total of 12.983.837 patients aged 60 or over included the studies selected for this systematic review. Most of the reported indications (54.1%) were for depression. The most reported adverse events were drowsiness (5–30%), dry mouth (1–37.5%), constipation (3.9–23.2%), urinary infection (8.8–24%), fractures (0.3–18.6%) and risk of death (0.28–1.7%). From the included randomized controlled trials, comparing mirtazapine with placebo, mirtazapine resulted in higher rates of dry mouth. Compared with amitriptyline, mirtazapine had lower risk of dry mouth and drowsiness, and a higher risk of constipation. Compared with fluoxetine, mirtazapine had higher rates of drowsiness and dry mouth.

Conclusions: This work provides full characterization of mirtazapine safety in older people, which may help healthcare providers better anticipate, prevent and manage adverse events in this population.