Systematic examination of off-target effects of antipsychotic medications associated with microbiome disruption and heightened bacterial infection risks

Francesca McDonagh; Elaine K Murray; Brian Hallahan; Georgios Miliotis

doi:10.1016/j.jpsychires.2025.05.046

Systematic examination of off-target effects of antipsychotic medications associated with microbiome disruption and heightened bacterial infection risks

J Psychiatr Res. 2025 May 24:189:171-183. doi: 10.1016/j.jpsychires.2025.05.046. Online ahead of print.

Authors

Francesca McDonagh¹, Elaine K Murray², Brian Hallahan³, Georgios Miliotis⁴

Affiliations

¹ Antimicrobial Resistance and Microbial Ecology Group, School of Medicine, University of Galway, Galway, Ireland.
² Personalised Medicine Centre, School of Medicine, C-TRIC, Altnagelvin Hospital, Ulster University, Derry, Londonderry, United Kingdom.
³ Discipline of Psychiatry, School of Medicine, University of Galway, Galway, Ireland.
⁴ Antimicrobial Resistance and Microbial Ecology Group, School of Medicine, University of Galway, Galway, Ireland; Centre for One Health, Ryan Institute, University of Galway, Galway, Ireland. Electronic address: georgios.miliotis@universityofgalway.ie.

PMID: 40499249
DOI: 10.1016/j.jpsychires.2025.05.046

Abstract

Objective: This systematic review aims to critically evaluate the link between antipsychotic drugs and bacterial infection risk, emphasising antimicrobial properties of antipsychotics, and microbiome changes that might heighten susceptibility to bacterial infections.

Methods: A systematic literature search was conducted across PubMed, Scopus, and Google Scholar, up to March 2024. Peer-reviewed articles that investigated the relationship between antipsychotics, their antimicrobial effects, microbiome alterations, and bacterial infection risk were included. Data extracted included antipsychotic type, infection risks, patient demographics, and study methodologies. Risk-of-bias assessments were performed using tools such as the Newcastle-Ottawa Scale and the SYRCLE risk-of-bias tool.

Results: The review analysed twenty-six studies detailing antimicrobial properties of antipsychotics, four studies on antipsychotic-induced microbiome alterations, and thirty-one studies assessing bacterial infection risk associated with antipsychotics. First-generation antipsychotics were observed to have broad antimicrobial properties, whereas second-generation antipsychotics primarily affected commensal bacteria. At least four antipsychotics were observed to disrupt the gut microbiota. A heightened risk of infection was observed among psychiatric cohorts as well as off-label antipsychotics use, with clozapine linked to a substantial increase in respiratory infection risk.

Discussion: Although antipsychotics remain indispensable in psychiatric care, their association with an increased risk of bacterial infections underscores the need for judicious prescribing and vigilant monitoring. The review identifies significant knowledge gaps attributable to inconsistent research methodologies, small study cohorts, lack of controls, and focus on a limited range of antipsychotics. Further standardised research is essential to deepen our understanding of these associations and to inform improved prescribing practices and risk mitigation strategies.

Keywords: Antimicrobial resistance; Antipsychotics; Bacterial infection; Microbiome; Respiratory infection.

Publication types

Review