rTMS及CBT-I对慢性失眠障碍患者治疗效果的随机对照研究

Efficacy of rTMS and CBT-I on patients with chronic insomnia disorder:a randomized controlled study

背景 目前,药物疗法是失眠障碍的一线治疗手段,但仍然存在着一定的不良反应。与药物治疗相比,重复经颅磁刺激(rTMS)和失眠的认知行为治疗(CBT-I)的不良反应较少、患者耐受性较好。目的 探讨rTMS与CBT-I治疗慢性失眠障碍的效果,以期为慢性失眠障碍患者提供更优的治疗方案。方法 选取2020年9月21日—2021年12月16日在内蒙古自治区精神卫生中心门诊或社区医院就诊的、符合《国际睡眠障碍分类第三版》(ICSD-3)诊断标准的慢性失眠障碍患者(n=50),同期在社区招募与患者组年龄和性别相匹配的健康人作为对照组(n=16)。采用随机数字表法将慢性失眠障碍患者分为rTMS组与CBT-I组各25例,分别接受为期6周的rTMS或CBT-I干预。于干预前和干预后,慢性失眠障碍患者接受多导睡眠监测(PSG)以及匹兹堡睡眠质量指数量表(PSQI)、失眠严重程度指数量表(ISI)、重复性成套神经心理状态测验(RBANS)评定。对患者组和对照组进行静息态磁共振成像(rs-fMRI)扫描,并进行静息态低频振幅(ALFF)分析。将患者组和对照组ALFF值差异有统计学意义的脑区作为感兴趣区域(ROI),将其作为种子点与患者全脑进行功能连接分析。结果 rTMS组和CBT-I组的PSQI评分、ISI评分以及RBANS中的即刻记忆、言语功能、延时记忆维度评分的时间效应均有统计学意义(F=41.160、69.615、47.923、12.090、28.193,P均<0.05);两组总睡眠时间的时间效应、睡眠效率的时间效应和组别效应以及N1%的时间效应均有统计学意义(F=8.995、12.414、4.342、7.806,P均<0.05)。干预后,CBT-I组睡眠效率高于干预前(t=-2.785,P<0.05)。rTMS组眶部额上回与左侧豆状壳核(t=4.991,P<0.05)、右内侧和旁扣带回(t=4.471,P<0.05)和右侧中央后回(t=4.922,P<0.05)之间的功能连接增强,CBT-I组眶部额上回与左侧额中回之间的功能连接增强(t=6.586,P<0.05)。结论 rTMS及CBT-I可能有助于改善慢性失眠障碍患者的失眠情况和认知功能。

Background To date,pharmacologic therapy is considered the standard first-line treatment for insomnia disorder,but there are still some concerns over the adverse reactions.Repetitive transcranial magnetic stimulation(rTMS)and cognitive behavioral therapy for insomnia(CBT-I)as an alternative to pharmacologic therapy have the advantages of fewer side effects and better patient tolerance in the treatment of chronic insomnia disorder.Objective To explore the clinical efficacy of rTMS and CBT-I on chronic insomnia disorder,so as to provide a novel therapeutic option for the treatment of chronic insomnia disorder.Methods A total of 50 patients with chronic insomnia disorder attending the outpatient clinic of Inner Mongolia Autonomous Region Mental Health Center or community hospital from September 21,2020 to December 16,2021 and fulfilling the International Classification of Sleep Disorders,third edition(ICSD-3)diagnostic criteria were enrolled.Additionally,16 age-and sex-matched healthy controls recruited from the community were set as control group.Patients were randomly divided into rTMS group and CBT-I group,25 cases in each group,and received rTMS or CBT-I intervention for 6 weeks respectively.At enrollment and completion of intervention,patients were subjected to Polysomnography(PSG),Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI)and Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).All participants underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans,and amplitude of low-frequency fluctuation(ALFF)was calculated.The brain regions with statistically different ALFF values between patient group and control group were chosen as regions of interest(ROIs),and whole-brain seed-based functional connectivity analyses were conducted.Results After a 6-week intervention in the two groups,the main effect of time was significant for PSQI(F=41.160,P<0.05),ISI(F=69.615,P<0.05)and RBANS immediate memory(F=47.923,P<0.05),language(F=12.090,P<0.05)and delayed memory indices(F=28.193,P<0.05).A significant main effect of time for total sleep time(F=8.995,P<0.05),a significant main effect of time for sleep efficiency(F=12.414,P<0.05),a significant main effect of group for sleep efficiency(F=4.342,P<0.05)and a significant main effect of time for N1%(F=7.806,P<0.05)were observed.Sleep efficacy in CBT-I group improved significantly from pre-to post-test(t=-2.785,P<0.05).Patients in rTMS group showed increased functional connectivity between the orbital superior frontal gyrus and other regions including left lentiform nucleus putamen(t=4.991,P<0.05),right median cingulate and paracingulate gyri(t=4.471,P<0.05)and right postcentral gyrus(t=4.922,P<0.05),and increased functional connectivity between the orbital superior frontal gyrus and left middle frontal gyrus was found in CBT-I group(t=6.586,P<0.05).Conclusion rTMS and CBT-I may help alleviate insomnia and improve cognitive function of patients with chronic insomnia disorder.