盐酸小檗碱附加治疗对抑郁症患者焦虑症状、睡眠质量的影响

Effects of berberine hydrochloride adjunctive therapy on anxiety symptoms and sleep quality inpatients with depressive disorder

目的 评价盐酸小檗碱(BBR)附加治疗对抑郁症患者焦虑、失眠的有效性及临床使用的安全性。方法 选取2022年9月—2023年10月河南省驻马店市第二人民医院门诊或住院病房的78例抑郁症患者为研究对象,采用随机双盲安慰剂对照临床试验的方法,按1∶1将入选患者随机分为BBR组(n=39)与安慰剂组(n=39),分别给予BBR和安慰剂,同时进行为期8周的联合选择性5-羟色胺再摄取抑制剂(SSRIs)类抗抑郁药治疗。在基线及2、4、6、8周使用汉密尔顿焦虑量表(HAMA)对患者焦虑症状进行评估。于基线及4、8周使用匹兹堡睡眠质量指数(PSQI)评价患者睡眠质量,采用便秘自评量表(PAC-SYM)评价患者BBR临床使用的安全性。采用重复测量方差分析比较组间(BBR组与安慰剂组)、组内(各个时间点)和交互作用(分组*时间)的影响。采用协方差分析和Wilcoxon秩和检验两组患者各时间点相对于基线的差异。采用二项Logistic回归分析两组患者的焦虑反应率和缓解率。采用Kaplan-Meier生存曲线评价两组患者焦虑反应和缓解所需的时间。结果 最终纳入68例抑郁症患者,BBR组与安慰剂组各34例,两组脱落率均为12.8%(5/39)。重复测量方差分析显示,BBR组6、8周的HAMA评分较安慰剂组降低,差异有统计学意义(P<0.05);协方差分析显示,BBR组与安慰剂组在6周[(11.44±6.15)分比(6.53±8.50)分,P<0.001]、8周[(11.29±5.94)分比(7.91±8.10)分,P=0.005]的HAMA评分变化差异有统计学意义。Logistic回归分析显示,BBR组的焦虑反应率在第6周(OR=8.99,95%CI:2.22~36.44,P=0.002)、缓解率在第8周(OR=3.45,95%CI:1.00~11.86,P=0.049)增加。但生存分析显示,两组患者焦虑的反应及缓解所需时间差异均无统计学意义(均P>0.05)。重复测量方差分析、协方差分析及Logistic回归分析显示,BBR组4、8周的PSQI评分及各个时间点的睡眠缓解率、反应率与安慰剂组比较,差异均无统计学意义(均P>0.05)。协方差分析显示,BBR组在4、8周的PAC-SYM评分相对基线评分的变化与安慰剂组比较,差异均无统计学意义(P>0.05)。结论 BBR附加治疗可能是改善抑郁症患者焦虑症状有效和安全的方法。

Objective To evaluate the efficacy and clinical safety of berberine hydrochloride(BBR)adjunctive therapy for anxiety and insomnia in patients with depressive disorder.Methods From September 2022 to October 2023,78 patients with depressive disorder in the outpatient or ward of the Zhumadian Second People's Hospital of Henan Province were selected as the research subject.Using a double-blind randomized placebo-controlled clinical trial method,the enrolled patients were randomly divided into a BBR group(n=39)and a placebo group(n=39)by a 1:1 ratio,were given BBR and placebo,respectively,and were treated with a combination of selective serotonin reuptake inhibitors(SSRIs)for 8 weeks.At baseline and weeks 2,4,6,and 8,the patient's anxiety symptoms were evaluated using the Hamilton Anxiety Scale(HAMA).Pitsburgh Sleep Quality Index(PSQI)was used to evaluate the sleep quality of patients at baseline and 4 and 8 weeks,and the Patient Assessment of Constipation Symptom(PAC-SYM)was used to evaluate the clinical safety of BBR.Repeated measures analysis of variance was used to compare the effects of inter group(BBR group and placebo group),intra group(at various time points),and interaction(group*time).Covariance analysis and Wilcoxon rank sum test were used to explore the differences between two groups of patients at different time points relative to baseline.Binary Logistic regression was used to analyze the anxiety response rate and relief rate of two groups of patients.Kaplan-Meier survival curve was used to evaluate the time required for anxiety response and relief in two groups of patients.Results A total of 68 patients with depressive disorder were included,with 34 cases in BBR group and 34 cases in placebo group,and the dropout rates in both groups were 12.8%(5/39).Repeated measures analysis of variance showed that compared with placebo group,the HAMA score of BBR group decreased at 6 and 8 weeks,and the difference was statistically significant(P<0.05).Covariance analysis showed that there were statistically significant differences in HAMA score changes between BBR group and placebo group at 6 weeks[(11.44±6.15)vs(6.53±8.50),P<0.001]and 8 weeks[(11.29±5.94)vs(7.91±8.10),P=0.005].Logistic regression showed that the anxiety response rate of BBR group increased at 6 weeks[OR=8.99,95%CI(2.22,36.44),P=0.002]and the relief rate increased at 8 weeks[0R=3.45,95%CI(1.00,11.86),P=0.049].Survival analysis showed that there was no statistically significant difference in the time required for the response and relief to anxiety between the two groups of patients(all P>0.05).Repeated measures analysis of variance,covariance analysis,and Logistic regression analysis showed that there was no statistically significant difference in PSQI scores,sleep relief rates,and response rates at different time points between BBR group and placebo group at 4 weeks and 8 weeks(all P>0.05).Covariance analysis showed that there was no statistically significant difference in the changes in PAC-SYM scores relative to baseline scores between BBR group and placebo group at weeks 4 and 8(P>0.05).Conclusions BBR adjunctive therapy may be an effective and safe method to improve anxiety symptoms in patients with depressive disorder.