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Bipolar Disorder (BD) is a mental disorder characterized by periods of depression and abnormally elevated moods. Recent studies proposed the existence of a correlation between inflammation, disease severity and response to antipsychotic therapy. The present study is aimed to investigate if treatment with second-generation antipsychotic, in monotherapy, influences the inflammatory process in BD patients. In 50 hospitalized BD patients who started monotherapy with second-generation antipsychotic, we investigated, after six-week of treatment, both clinical outcomes and change in inflammatory markers such as C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). We observed a significant improvement of clinical symptoms (measured through MADRAS, YMRS, CGI and BPRS scales) in all treated patients. Moreover, we found that at the time of enrolment BD patients showed higher CRP levels compared to reference value, and that after 6 weeks of antipsychotic treatment CRP (but not ERS) plasma levels were significantly reduced returning to reference levels. The present exploratory study indicates that monotherapy with antipsychotic drugs reduces, not only BD symptoms, but also an inflammatory marker such as PCR. The evaluation of relationship between antipsychotic treatment and patients inflammatory conditions could be usefulness in clinical practice, both providing a marker to drug response, and permitting the identification of new targets in BD therapy., (Copyright © 1964–2022 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)