塞来昔布辅助治疗精神分裂症的有效性和安全性及机制分析

The efficacy,safety,and mechanism of celecoxib as an adjunctive treatment for schizophrenia

目的探究塞来昔布辅助治疗精神分裂症的有效性、安全性及可能机制。方法前瞻性收集2019年4月至2020年10月在新乡医学院第二附属医院住院的90例精神分裂症患者的资料,采用随机数字表法将患者分为安慰剂组和塞来昔布辅助治疗组。安慰剂组有46例完成6周随访,其中男29例,女17例,年龄21~34(27.46±6.50)岁;塞来昔布组有44例完成6周随访,其中男32例,女12例,年龄21~39(30.52±8.69)岁。采用阳性与阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评估2组患者的精神病症状,对比分析治疗后PANSS评分变化量以评估塞来昔布辅助治疗的有效性。采集体重、糖脂等代谢相关指标,血压、心电、血常规等心血管相关指标,利用不良反应量表评估不良反应,进而分析塞来昔布辅助治疗的安全性。使用酶联免疫吸附试验检测患者血清肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-4、干扰素-γ(interferon-γ,IFN-γ)水平,采用Pearson相关分析2组患者细胞因子水平与PANSS评分、PANSS减分率[(治疗前评分-治疗后评分)/治疗前评分×100%]及糖脂代谢指标的关系,分析炎症在塞来昔布辅助治疗中的作用。结果塞来昔布辅助治疗组6周PANSS阳性评分变化量显著高于安慰剂组[(-8.00±6.12)分比(-4.78±5.19)分,H=-0.55,P=0.009]。塞来昔布辅助治疗组6周体重、体重指数、总胆固醇、甘油三酯的变化量均显著低于安慰剂组(F=-7.37、-7.30、2.56、-2.54,均P<0.05);塞来昔布辅助治疗未发现严重不良反应。安慰剂组中,基线期TNF-α与基线期阴性症状、6周PANSS减分率呈正相关(r=0.260、0.330;均P<0.05),与6周体重呈负相关(r=-0.311;P<0.05);基线期IL-4水平与6周PANSS总分、6周PANSS阴性症状评分呈正相关(r=0.320、0.397;均P<0.05),与PANSS减分率、6周血糖呈负相关(r=-0.316、-0.331;均P<0.05);6周IFN-γ水平与低密度脂蛋白水平呈负相关(r=-0.306;P<0.05)。塞来昔布辅助治疗组无该相关性。结论塞来昔布辅助治疗可改善精神分裂症阳性症状,未见不良反应。炎症状态与精神分裂症症状、疗效以及代谢不良反应相关。

Objective To investigate the efficacy,safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods 90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table.In the placebo group,46 patients(29 males,17 females;aged 21-34,mean age 27.46±6.50 years)completed a 6-week follow-up.In the celecoxib group,44 patients(32 males,12 females;aged 21-39,mean age 30.52±8.69 years)completed a 6-week follow-up.The Positive and Negative Syndrome Scale(PANSS)was used to assess psychiatric symptoms in both groups.Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib.Metabolic indicators such as weight,body mass index,waist circumference and plasm glucolipid,as well as cardiovascular indicators like blood pressure,electrocardiogram and routine blood tests,and adverse events were collected for the safety evaluation.Serum tumor necrosis factor-α(TNF-α),Interleukin-4(IL-4)and interferon-γ(IFN-γ)were also tested.Pearson correlation analysis was used to explore the relationship between cytokine levels,PANSS score,PANSS reduction rate[(pre-treatment score-post-treatment score)/pre-treatment score×100%],and the safety measurements in the two groups,analyzing the role of inflammation in celecoxib adjunctive therapy.Results The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group(-8.00±6.12 vs-4.78±5.19,H=-0.55,P=0.009).The weight changes,body mass index,total cholesterol,and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group(F=-7.37,-7.30,2.56,-2.54;all P<0.05).No serious adverse events were found in celecoxib adjuvant therapy.In the placebo group,baseline TNF-αlevels were positively correlated with baseline negative symptoms and PANSS reduction rate(r=0.260 and 0.330,both P<0.05),and negatively correlated with the 6-week weight(r=-0.311,P<0.05);baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score(r=0.320 and 0.397,both P<0.05),and negatively correlated with PANSS reduction rate and 6-week blood glucose(r=-0.316 and-0.331,both P<0.05);Six-week IFN-γlevels were negatively correlated with low-density lipoprotein levels(r=-0.306,P<0.05).And no such correlation was found in celecoxib adjuvant group.Conclusion Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions.Inflammatory state is related to schizophrenia symptoms,treatment efficacy and metabolic abnormalities.