Can Cognitive Behavioral Therapy for Insomnia (CBT-I) Reduce Biomarkers of Inflammation? A Systematic Review of Randomized Controlled Trials

Objective: Individuals with insomnia show increased concentrations of pro-inflammatory biomarkers including C-reactive protein (CRP), interleukin-1(3 (IL-(3), inter-leukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) compared to controls. Insomnia-related inflammation may contribute to poorer health outcomes and may need to be clinically addressed. Whether guideline-recommended insomnia treatment (i.e. cognitive behavior therapy for insomnia, CBT-I) can reduce inflammation is unclear. Method: This systematic review synthesize and assessed the risk of bias of randomized controlled trials (RCTs) reporting on the effects of CBT-I on CRP, IL-1(3, IL-6, and TNF-alpha. PubMed, Scopus, CINAHL, and PsycINFO were searched up to June 2025. Results: From the initial 2206 records retrieved, 11 RCTs were included. IL-6 (k = 7) and CRP (k = 5) were the most assessed markers of inflammation while fewer RCTs assessed TNF-alpha (k = 4) and IL-1(3 (k = 3) in the context of CBT-I. Results from RCTs largely varied, with CBT-I more consistently reported to decrease CRP than cytokines. The synthesis of outcome using meta-analysis was precluded by considerable differences in population, measurement, and outcome reporting. Conclusions: We conclude that research on CBT-I and inflammation is still developing and propose a research agenda aimed at advancing our understanding of the potential anti-inflammatory properties of CBT-I, the mediators of change, and implications for comorbidity prevention.