Effects of new hypnotic drugs on cognition: A systematic review and network meta-analysis

Abstract

Background: Insomnia is a common disease, and the application of various types of sleeping pills for cognitive impairment is controversial, especially as different doses can lead to different effects. Therefore, it is necessary to evaluate the cognitive impairment caused by different sleeping pills to provide a theoretical basis for guiding clinicians in the selection of medication regimens.

Objective: To evaluate whether various different doses (low, medium and high) of anti-insomnia drugs, such as the dual-orexin receptor antagonist (DORA), zopiclone, eszopiclone and zolpidem, induce cognitive impairment.

Methods: The PubMed, Embase, Scopus, Cochrane Library, and Google Scholar databases were searched from inception to September 20th, 2022 for keywords in randomized controlled trials (RCTs) to evaluate the therapeutic effects of DORA, eszopiclone, zopiclone and zolpidem on sleep and cognitive function. The primary outcomes were indicators related to cognitive characteristics, including scores on the Digit Symbol Substitution Test (DSST) and daytime alertness. The secondary outcomes were the indicators associated with sleep and adverse events. Continuous variables were expressed as the standard mean difference (SMD). Data were obtained through GetData 2.26 and analyzed by Stata v.15.0.

Results: A total of 8702 subjects were included in 29 studies. Eszopiclone_high significantly increased the daytime alertness score (SMD = 3.00, 95 % CI: 1.86 to 4.13) compared with the placebo, and eszopiclone_high significantly increased the daytime alertness score (SMD = 4.21, 95 % CI: 1.65 to 6.77; SMD = 3.95, 95 % CI: 1.38 to 6.51; SMD = 3.26, 95 % CI: 0.38 to 6.15; and SMD = 3.23, 95 % CI: 0.34 to 6.11) compared with zolpidem_low, zolpidem_high, DORA_low, and eszopiclone_mid, respectively. Compared with the placebo, zopiclone, zolpidem_mid, and eszopiclone_high, DORA significantly increased the TST (SMD = 2.39, 95 % CI: 1.11 to 3.67; SMD = 6.00, 95 % CI: 2.73 to 9.27; SMD = 1.89, 95 % CI: 0.90 to 2.88; and SMD = 1.70, 95 % CI: 0.42 to 2.99, respectively).

Conclusion: We recommend DORA as the best intervention for insomnia because it was highly effective in inducing and maintaining sleep without impairing cognition. Although zolpidem had a more pronounced effect on sleep maintenance, this drug is better for short-term use. Eszopiclone and zopiclone improved sleep, but their cognitive effects have yet to be verified.

Keywords: Cognition; DORA; Dose–response; Insomnia; Meta-analysis.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study search and selection for the meta-analysis.

Fig. 2

Network relationship diagram. The larger the circle, the more treatment measures were used. Thicker lines between two points indicate more studies including both topics.