Impact of psychopharmacotherapy on systemic inflammatory response markers in psychosomatic patients: A retrospective study

INTRODUCTION. The safety of pharmacotherapy in patients with mental disorders is critical for accurate assessment of systemic inflammatory processes. Psychopharmacotherapy may modulate the immune response, potentially masking systemic inflammatory response (SIR) signs in patients with psychosomatic profile. This phenomenon complicates the differential diagnostic process and the selection of an appropriate treatment strategy.

AIM. To evaluate the effect of pre-admission psychotropic medication use on key markers of systemic inflammatory response (body temperature, leukocytosis, and C-reactive protein (CRP) levels) to enhance the safety of psychotropic pharmacotherapy and optimize therapeutic strategies in hospitalized patients with mental disorders.

MATERIALS AND METHODS. This single-center retrospective study analyzed data from 850 patients hospitalized between January 2024 and March 2025 with suspected infectious complications or decompensation of somatic pathology. Five classes of psychopharmacotherapeutic agents were evaluated: antipsychotics (n=270), antidepressants (n=56), antiepileptics (n=94), anxiolytics (n=15), and antiparkinsonian agents (n=63). Associations with febrile response (<37 °C, ≤38 °C, >38 °C), leukocytosis, and elevated CRP levels were assessed using the Pearson χ² test, Fisher's exact test, and the linear-by-linear association test.

RESULTS. No single drug class affected all three markers of SIR simultaneously. Antidepressant use was associated with a significant linear trend toward reduced fever severity (p=0.024). Antiepileptic use was associated with a lower incidence of leukocytosis (p=0.039). Polytherapy (use of ≥3 medications) was significantly associated with a decrease in leukocyte counts (p=0.008) and an increase in CRP levels (p=0.006). Among individual agents, chlorprothixene and chlorpromazine were associated with higher, while risperidone was associated with lower, SIR parameter values. CRP levels during inflammation remained consistently elevated and were not influenced by psychotropic medication use.

CONCLUSIONS. Routine psychopharmacotherapy is not a universal confounding factor that distorts the picture of systemic inflammation. The effects are selective and most pronounced in the context of polytherapy. CRP, as the most stable marker, can serve as an objective indicator of inflammation, and data on the effects of individual antipsychotics on SIR markers can be used to optimize therapeutic strategies in patients with comorbid mental and somatic disorders.

1. Sikora JP, Karawani J, Sobczak J. Neutrophils and the systemic inflammatory response syndrome (SIRS). Int J Mol Sci. 2023;24(17):13469. https://doi.org/10.3390/ijms241713469

2. Benlamkaddem S, Doughmi D, Tlamçani I, et al. The challenging aspect of macrophage activation syndrome in the setting of sepsis or systemic inflammatory response syndrome (SIRS). Cureus. 2023;15(3):e36228. https://doi.org/10.7759/cureus.36228

3. Ye J, Hu X, Wang Z, et al. The role of mtDAMPs in the trauma-induced systemic inflammatory response syndrome. Front Immunol. 2023;14:1164187. https://doi.org/10.3389/fimmu.2023.1164187

4. Burghardt KJ, Mando W, Seyoum B, et al. The effect of antipsychotic treatment on hormonal, inflammatory, and metabolic biomarkers in healthy volunteers: A systematic review and meta-analysis. Pharmacotherapy. 2022;42(6):504–13. https://doi.org/10.1002/phar.2689

5. Rok-Bujko P. Molecular mechanisms of antipsychotics — their influence on intracellular signaling pathways, and epigenetic and post-transcription processes. Postep Psychiatr Neurol. 2022;31(2):74–84. https://doi.org/10.5114/ppn.2022.117963

6. Nava RG, Adri AS, Filgueiras IS, et al. Modulation of neuroimmune cytokine networks by antidepressants: implications in mood regulation. Transl Psychiatry. 2025;15(1):314. https://doi.org/10.1038/s41398-025-03532-y

7. Tatayeva R, Ossadchaya E, Sarculova S, et al. Psychosomatic aspects of the development of comorbid pathology: A review. Med J Islam Repub Iran. 2022;36:152. https://doi.org/10.47176/mjiri.36.152

8. Tolokonin AO. Models of pathogenesis of psychosomatic disorders and the concept of psychosomatic scenario. Medical Herald of the South of Russia. 2023;14(2):61–6 (In Russ.). https://doi.org/10.21886/2219-8075-2023-14-2-61-66

9. Bleibel L, Sokołowska P, Henrykowska G, et al. Unveiling the anti-inflammatory effects of antidepressants: A systematic review of human studies over the last decade. Pharmaceuticals (Basel). 2025;18(6):867. https://doi.org/10.3390/ph18060867

10. Köhler CA, Freitas TH, Stubbs B, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: Systematic review and meta-analysis. Mol Neurobiol. 2018;55(5):4195–206. https://doi.org/10.1007/s12035-017-0632-1

11. Almeida IB, Gomes IA, Shanmugam S, et al. Inflammatory modulation of fluoxetine use in patients with depression: A systematic review and meta-analysis. Cytokine. 2020;131:155100. https://doi.org/10.1016/j.cyto.2020.155100

12. Himmerich H, Bartsch S, Hamer H, et al. Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro. J Psychiatr Res. 2013;47(11):1751–9. https://doi.org/10.1016/j.jpsychires.2013.07.026

13. Ichiyama T, Okada K, Lipton JM, et al. Sodium valproate inhibits production of TNF-alpha and IL-6 and activation of NF-kappaB. Brain Res. 2000;857(1–2):246–51. https://doi.org/10.1016/s0006-8993(99)02439-7

14. Marcinowicz P, Więdłocha M, Zborowska N, et al. A Meta-analysis of the influence of antipsychotics on cytokines levels in first episode psychosis. J Clin Med. 2021;10(11):2488. https://doi.org/10.3390/jcm10112488

15. Subbanna M, Shivakumar V, Venugopal D, et al. Impact of antipsychotic medication on IL-6/STAT3 signaling axis in peripheral blood mononuclear cells of drug-naive schizophrenia patients. Psychiatry Clin Neurosci. 2020;74(1):64–9. https://doi.org/10.1111/pcn.12938

16. Stapel B, Sieve I, Falk CS, et al. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res. 2018;105:95–102. https://doi.org/10.1016/j.jpsychires.2018.08.017

17. Patel S, Keating BA, Dale RC. Anti-inflammatory properties of commonly used psychiatric drugs. Front Neurosci. 2023;16:1039379. https://doi.org/10.3389/fnins.2022.1039379