Exploring the Influence of Inflammation on the Pharmacokinetics of Antidepressants and Antipsychotics: A Systematic Review

Introduction/Objective: Strong evidence suggests that inflammation can affect the activity of Cytochrome P450 (CYP) isoforms responsible for the metabolism of numerous psychiatric drugs. This is likely of particular importance in conditions such as Major Depressive Disorder (MDD), where a relevant percentage of patients report non-response to treatment. Thus, the existing knowledge on the impact of inflammation on medications used in MDD, and metabolised via these pathways (e.g., antidepressants and antipsychotics), needs to be further evaluated. Methods: In this systematic review, the PubMed, Scopus, and Web of Science databases were screened, and published articles between January 1st, 2010, and May 25th, 2025, were retrieved. The research strategy was based on combinations of key terms related to pharmacokinetics, inflam-mation, and antidepressants or antipsychotics. A total of five observational and cohort studies were included, along with ten case series or case reports that investigated the topic in human subjects. Results/Discussion: The available evidence appears unbalanced and severely limited for antidepres-sants. The single study available suggests limited changes in the pharmacokinetics of citalopram and venlafaxine in inflammatory conditions. By contrast, the available data for antipsychotics suggest variable effects of inflammation on their pharmacokinetics. In particular, clozapine is associated with substantial increases in plasma concentrations. Overall, the relationship between inflammation and the pharmacokinetics of psychiatric drugs appears to be complex. Furthermore, much of the available data is plagued by limitations, such as small sample sizes and retrospective designs, as well as poor characterisation of patients' genetic and immunological profiles. Conclusion: Considering the current, very limited evidence base, especially for antidepressants, the necessity for larger prospective studies remains pressing. Further studies should incorporate pharmacogenetics and immunological profiling to better support clinical practice recommendations.