重复经颅磁刺激治疗原发性失眠的安慰剂效应

Placebo response of repetitive transcranial magnetic stimulation for primary insomnia

目的系统评价重复经颅磁刺激(rTMS)治疗原发性失眠的安慰剂效应。方法计算机检索PubMed、EMBASE、Cochrane Library和中国知网(CNKI)数据库,筛选符合纳入和排除标准的评价rTMS治疗原发性失眠效果的文献,最终纳入9篇文献,共计580例原发性失眠患者。采用Newcastle-Ottawa量表进行文献质量评价,应用Stata 15.0软件进行数据的meta分析。结果真rTMS的匹兹堡睡眠质量指数(PSQI)的合并效应量(Hedges′g)为-1.44(95%CI=-1.63^-1.26)(P<0.001),与伪rTMS比较,其发生不良事件的相对风险(RR)为1.55(95%CI=0.90~2.67)(P=0.11)。伪rTMS的安慰剂效应显著,其PSQI、睡眠效率(SE)、睡眠潜伏期(LPS)、总睡眠时间(TST)和睡眠后觉醒时间(WASO)的效应量均大于0.8。rTMS的效应量中安慰剂效应占比高达73.5%(95%CI=50.8%~96.2%)。伪rTMS对睡眠结构的影响中,深度睡眠(NREM-3)的改善几乎均为安慰剂效应的作用(95.%),但安慰剂效应对REM睡眠几乎没有影响(3.7%)。伪rTMS和真rTMS的效应量,在30 d内,都有随治疗时间的增加而增加的趋势(P=0.09)。结论rTMS是治疗原发性失眠的有效方法,然其效应量的绝大部分根源于安慰剂(伪rTMS)效应,真正的rTMS效应仅占总治疗效应的25%左右。安慰剂效应在30 d内有随着治疗时间的延长而增加的趋势。

Objective To examine the placebo response of sham repetitive transcranial magnetic stimulation(rTMS) for the treatment of primary insomnia.Methods We performed a comprehensive literature search for clinical trials evaluating the efficacy of rTMS addressing primary insomnia. To pool effect size estimates(Hedges′g) of active rTMS and sham rTMS across studies for outcome measures, a meta-analysis was done according to the Cochrane guideline. Results The rTMS significantly improved insomnia symptoms in active rTMS group, and the pooled effect size of Pittsburgh Sleep Quality Index(PSQI) was-1.44(95% CI:-1.63,-1.26)(P<0.001), and the relative risk(RR) of rTMS was 1.55(95% CI: 0.90, 2.67)(P=0.11). The placebo response was also significant to reduce insomnia symptoms in sham rTMS group with Hedges′g of more than 0.8 for PSQI, SE, LPS, TST, and WASO. And 73.5%(95% CI: 50.8%, 96.2%) of the effect size of active rTMS was actually produced by sham rTMS.Conclusion RTMS is an effective method for the treatment of primary insomnia, but most of its effect amount is due to the effect of placebo(pseudo rTMS). The real rTMS effect only accounts for about 25% of the total treatment effect. The placebo effect increased with the prolongation of treatment time within 30 days.