Adjunctive Celecoxib For Schizophrenia:A Clinical Research Of Randomized,Double-blind,Placebo-controlled Trials

BackgroundSchizophrenia is a severe degenerative mental illness affecting approximately 1% of the world’s population.The etiology of schizophrenia is unknown.The immunoinflammation hypothesis serves as an important hypothesis for the etiology of schizophrenia and get more and more research support.This hypothesis is based on the increased levels of peripheral inflammatory cytokines in schizophrenic patients.Celecoxib is a new generation of non-steroidal anti-inflammatory analgesics that inhibit prostaglandin production by selective inhibition of cyclooxygenase-2(COX-2),which can be regulated by regulating glutamatergic neurotransmission Inflammatory response;and several RCTs reported that compared with placebo,antipsychotics combined with celecoxib can significantly reduce the patient’s psychiatric symptoms,PANSS scores and improve cognitive function,and safety assessment also shows that celecoxib is well tolerated.Observe the effect of celecoxib in the treatment of schizophrenia in the acute phase and the changes of serum inflammatory factors,compare the differences between the two therapeutic effects,and further explain the inflammatory hypothesis of schizophrenia.ObjectivesObserve the clinical efficacy and safety of celecoxib in the treatment of first-episode schizophrenic patients with risperidone,and try to explore its mechanism.The differences in the levels of inflammatory cytokines in different treatment groups were compared,and the clinical significance of this difference was analyzed to explore whether it was related to the impact on the body’s immune mechanismMethods1.Using the Randomized controlled trials,100 first-episode schizophrenic patients in according with diagnostic criteria for schizophrenia in line with the tenth of international classification of diseases(ICD-10)were randomly divided into celecoxib plus risperidone and placebo plus risperidone groups.The celecoxib group was treated with celecoxib 0.2 g/d combined with risperidone 4-6 mg/d;the placebo group was treated with single risperidone 4-6 mg/d,Positive and negative symptom scale(PANSS)scores were assessed before and 4、6weeks after treatment.TESS scores were assessed before and 4,6weeks after treatment.2.Draw peripheral venous blood 5ml at 6:30-7:30 in the morning before and 4 6weeks after treatment,centrifuge and package the upper plasma,store at-80℃.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α,INF γ,IL-4,IL-1 beta,IL-6 and IL-17 in serum of patients.3.Use the mean±standard deviation to indicate the measurement data.The data differences between two groups were compared by independent-sample T test,and the data of the different time nodes were compared by Repeated measurement analysis of ANOVA.All results were two-sides test,and the size of a test were α=0.05.SPSS 23.0 statistical software were used for all the data analysis.Results1.There was no statistical difference between the two groups in terms of age,gender,and education level(P>0.05);there was no significant difference between the baseline PANSS total scores and other ratings(P>0.05).2.After 4 weeks of treatment,the PANSS total score,PANSS positive score,PANSS negative score and general pathology scores in both groups were significantly lower than those in baseline(P <0.05);After 6 weeks of treatment,the PANSS total score,PANSS positive score,PANSS negative score,and general pathology scores in both groups were significantly decreased compared with baseline(P<0.05);between the two groups,after 6 weeks of celecoxib treatment The total PANSS score and PANSS negative score in the Methods celecoxib group were lower than those in the placebo group(P<0.05).There was no significant difference in the adverse reactions and combined use of the two groups(P>0.05).3.After 6 weeks of treatment,the levels of inflammatory cytokines TNF-α,INF-γ and IL-17 in peripheral blood were significantly decreased in the two groups(P<0.05),and the TNF-α levels in celecoxib group were lower than those in placebo group.TNF-α decreased significantly(P<0.05).There was no significant difference in the levels of INF-γ and IL-17 between the two groups(P>0.05).The levels of IL-1β,IL-4 and IL-6 in both groups showed a decreasing trend,but there was no statistical significance(P>0.05).4.After 6 weeks of treatment,the changes of TNF-α in the peripheral blood of both groups were correlated with the changes of the total PANSS scores;the correlations between the changes of INF-γ in peripheral blood and the PANSS negative scores were related in both groups;no related trends were found in other inflammatory factors.Conclusions1.Celecoxib combined with risperidone in the treatment of patients with first-episode schizophrenia contributes to the improvement of psychiatric symptoms,negative symptoms are more prominent.2.Celecoxib combined with risperidone causes decreased levels of inflammatory cytokines in first-episode schizophrenic patients.3.Celecoxib can assist in the treatment of patients with first-episode schizophrenia.