Assessing sleep-wake survival dynamics in relation to sleep quality in a placebo-controlled pharmacological intervention study with people with insomnia and healthy controls

Psychopharmacology (Berl). 2021 Jan;238(1):83-94. doi: 10.1007/s00213-020-05660-3. Epub 2020 Sep 17.

Abstract

Rationale: The mechanisms underlying impaired sleep quality in insomnia are not fully known, but an important role for sleep fragmentation has been proposed.

Objectives: The aim of this study is to explore potential mechanisms of sleep fragmentation influencing alterations of perceived sleep quality.

Methods: We analyzed polysomnography (PSG) recordings from a double-blind crossover study with zopiclone 7.5 mg and placebo, in elderly participants with insomnia complaints and age-matched healthy controls. We compared survival dynamics of sleep and wake across group and treatment. Subsequently, we used a previously proposed model to estimate the amount of sleep onset latency (SOL) misperception from PSG-defined sleep fragmentation. Self-reported and model-estimated amount of SOL misperception were compared across group and treatment, as well as model prediction errors.

Results: In the zopiclone night, the average segment length of NREM sleep was increased (group F = 1.16, p = 0.32; treatment F = 8.89, p < 0.01; group x treatment F = 0.44, p = 0.65), while the segment length of wake was decreased (group F = 1.48, p = 0.23; treatment F = 11.49, p < 0.01; group x treatment F = 0.36, p = 0.70). The self-reported and model-estimated amount of SOL misperception were lower during the zopiclone night (self-reported group F = 6.08, p < 0.01, treatment F = 10.8, p < 0.01, group x treatment F = 2.49, p = 0.09; model-estimated F = 1.70, p = 0.19, treatment F = 16.1, p < 0.001, group x treatment F = 0.60, p = 0.55). The prediction error was not altered (group F = 1.62, p = 0.20; treatment F = 0.20, p = 0.65; group x treatment F = 1.01, p = 0.37).

Conclusions: Impaired subjective sleep quality is associated with decreased NREM stability, together with increased stability of wake. Furthermore, we conclude that zopiclone-induced changes in SOL misperception can be largely attributed to predictable changes of sleep architecture.

Keywords: Insomnia; Sleep fragmentation; Sleep onset latency; Sleep state misperception; Zopiclone.

MeSH terms

  • Adult
  • Aged
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / therapeutic use*
  • Clinical Trials as Topic
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use*
  • Polysomnography
  • Self Report
  • Sleep Deprivation / prevention & control
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep, REM / drug effects*

Substances

  • Azabicyclo Compounds
  • Piperazines
  • zopiclone