Efficacy and Placebo Response of Multimodal Treatments for Primary Insomnia: A Network Meta-Analysis

Pharmacotherapy, psychotherapy, and complementary therapy have been used for primary insomnia. However, the efficacy and placebo response are not exactly clear because of limited clinical data. We therefore conducted a systematic review to examine the efficacy and placebo response of multimodal treatments.

We performed a comprehensive literature search for randomized placebo-controlled clinical trials evaluating the efficacy of multimodal treatments addressing primary insomnia. To pool effect size estimates (Hedges' g) of active and placebo conditions across studies for outcome measures, a meta-analysis was done according to the Cochrane guideline.

The results of network meta-analysis for sleep efficiency showed that orexin receptor antagonists had the maximum effect size of 1.35 (95% confidence interval [CI], 0.88-1.82), followed by γ-aminobutyric acid agonists of 1.28 (95% CI, 0.85-1.71), cognitive behavioral therapy for insomnia of 1.07 (95% CI, 0.10-2.05), acupuncture of 0.64 (95% CI, -0.17 to 2.36), and repetitive transcranial magnetic stimulation of 0.61 (95% CI, -0.52 to 1.75), respectively. However, the placebo response was also significant and robust to improve insomnia symptoms, and 65.9% (95% CI, 49.3%-82.5%) of the effect size of multimodal treatments was actually produced by placebo conditions.

The pharmacotherapy seems the most effective in improving sleep efficiency. However, the optimal therapeutic regimen is still uncertain. In addition, the placebo response is significant and robust in treatments of primary insomnia.