An increase in C-reactive protein levels during antidepressant treatment predicts treatment non-response in major depressive disorder

Background One-third of patients with major depressive disorder (MDD) exhibit low-grade inflammation as reflected by C-reactive protein (CRP) concentrations > 3 mg/L. We explored whether CRP changes from baseline to week one of antidepressant treatment (ΔCRP) can serve as a marker of treatment response.

CRP plasma levels were measured at baseline and after the first week of treatment in 33 MDD patients and correlated with patients’ Hamilton depression scale (HAM-D), while adjusting for age, gender and body mass index. The early and final antidepressant responses were defined as a > 25% and > 50% HAM-D score reduction at week one and four of treatment compared to baseline, respectively. We compared baseline and week-one CRP levels with the paired t-test within responders and non-responders separately and ΔCRP between the groups with the ANCOVA.

Higher ΔCRP correlated with lower final ΔHAM-D scores (r = −0.5, p = 0.006). Non-responders showed higher ΔCRP – but not baseline and week one CRP – than responders (p = 0.018, Cohen’s d = 1.1). A ΔCRP increase was observed in 13/16 (81%) non-responders and 7/17 (41%) responders (Fisher’s exact test’s p = 0.03). A ΔCRP increase combined with an early non-response was observed in 13/16 (81%) non-responders and 1/17 (6%) responders (p < 0.0001).

Rather early ΔCRP at week one than baseline CRP might be indicative of treatment response at week four, especially if combined with early ΔHAM-D. In the future, ΔCRP could be introduced into psychiatric practice to guide treatment plans. Competing Interest Statement The authors have declared no competing interest. Funding Statement YR and MD were supported by the Dutch Research Council (NWO) Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of the Ludwig Maximilian University of Munich gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes ↵* shared co-authorship Data Availability All data produced in the present work are contained in the manuscript