Insomnia drug lemborexant reduces the gap between perceived and actual sleep

A study of individuals suffering from insomnia in Japan found that a 12-week treatment with lemborexant improved both objective and subjective sleep parameters. It also reduced sleep-wake state discrepancy, potentially leading to improved daytime functioning. The paper was published in Psychopharmacology.

Insomnia is a sleep disorder characterized by persistent difficulty falling asleep, staying asleep, or obtaining sleep that feels sufficiently restorative, despite having an adequate opportunity to sleep. It can lead to daytime problems such as fatigue, irritability, difficulty concentrating, reduced motivation, and poorer overall functioning.

Insomnia may develop in response to stress, illness, changes in routine, or other life events, but it can persist after the original trigger has disappeared. Worrying about sleep, spending excessive time in bed, irregular sleep schedules, and becoming highly alert to signs of sleeplessness can all help maintain the problem.

An important feature of insomnia is that people’s perception of their sleep does not always match what objective sleep measurements show. This phenomenon, known as sleep-wake discrepancy, occurs when a person feels that they were awake for much longer or slept much less than objective measurement tools indicate.

Study author Kent Naito and his colleagues conducted a secondary analysis of the FLUID study data, specifically evaluating the effects of lemborexant on treating sleep-wake state discrepancy in middle-aged and older individuals suffering from insomnia. Lemborexant is a prescription insomnia medication that promotes sleep by blocking orexin receptors, thereby reducing the brain’s wake-promoting signaling. Orexin receptors are receptors in the brain which are activated by specific biochemical compounds that regulate the sleep-wake cycle (among other things).

The FLUID study was a 12-week investigation of the effects of lemborexant involving 29 individuals suffering from insomnia. The participants’ average age was 58.5 years, and 15 of them were men.

Study participants underwent objective and subjective sleep assessments at the start of the study, and again 4 and 12 weeks after starting the lemborexant medication. They received a starting dose of 5mg of lemborexant after the initial assessments, and were allowed to increase the dose to 10mg if it was ineffective after 4 weeks.

Participants’ objective sleep parameters were assessed using Zmachine Insight+ (General Sleep, Cleveland, OH, USA), a single-channel EEG (a device that records electrical activity in the brain) that monitors sleep. Participants also kept electronic sleep diaries in which they reported different subjective sleep parameters.

Sleep-wake state discrepancy was calculated by comparing the objective sleep parameters and the participants’ subjective reports. Study participants also completed assessments of sleep quality (the Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth Sleepiness Scale), and depressive symptoms (the Beck Depression Inventory-II).

Results showed that lemborexant treatments improved both objective and subjective sleep parameters 12 weeks after the start of treatments. The discrepancy between subjective and objective measures of how long it took participants to fall asleep was also reduced at week 12. However, the discrepancy between subjective and objective measures of time spent awake during the night did not change significantly among the baseline, 4-week, and 12-week marks.

Interestingly, participants who reported a greater reduction in daytime sleepiness tended to be the participants who also saw a greater reduction in the discrepancy between their subjective and objective total sleep time. However, the reduction in this discrepancy was not associated with improved subjective sleep quality.

“The present findings suggest that lemborexant treatment reduces sleep-wake state discrepancy, which may be associated with improved daytime functioning in patients with insomnia disorder,” the study authors concluded.

The study contributes to the scientific knowledge about the effects of lemborexant. However, it was conducted on a relatively small number of participants. Additionally, the study did not include a control group or control condition. Therefore, it remains unknown whether the observed effects are solely the results of the lemborexant treatment or if they represent natural developments (or developments caused by other factors) of the studied sleep quality indicators over time.

The paper, “Effect of lemborexant on sleep-wake state discrepancy in participants with insomnia disorder,” was authored by Kent Naito, Kunihiro Iwamoto, Seiko Miyata, Ippei Okada, Keita Kawai, Akihiro Fujimoto, Yuki Kogo, Daisuke Mori, Nao Matsuyama, Masahiko Ando, Norio Ozaki, and Masashi Ikeda.