Dynamic features of placebo effects addressing persistent insomnia disorder: A meta-analysis of placebo-controlled randomized clinical trials

It has been accepted knowledge that placebo effects have been significant in insomnia clinical trials. However, the dynamic features of placebo effects have not been clarified. Our aim was therefore to conduct a meta-analysis of placebo-controlled randomized clinical trials to characterize the dynamic features of placebo effects addressing persistent insomnia disorder. We performed a comprehensive literature search for randomized, placebo-controlled, double-blind clinical trials evaluating the efficacy of therapeutic regimens addressing persistent insomnia disorder. We pooled separate effect size estimates (Hedge'sg) of placebo and regimen conditions across trials for outcome measures, and multilevel mixed-effects models were used to explore potential sources of heterogeneity. The placebo effects were significant and robust to improve the symptoms of insomnia, and subjective measures were significantly smaller than objective measures (p < .001), but placebo response rates were nearly identical between subjective and objective measures. The overall placebo effects were influenced by publication year (p = .015), treatment duration (p = .010), sample size (p < .001) and therapeutic regimen (p < .001). Placebo effects showed a diphasic feature within treatment duration: initially a decrease and subsequently being stable; a sustained decline trend after withdrawals; and a steady-to-upward trend for a mixed therapeutic regimens in a large-scale period over decades. The dynamic features of placebo effects addressing persistent insomnia disorder may lead to the development and validation of dosing strategies that require less medication exposure to maintain clinical effects.