Patients with chronic insomnia may have an overactive brain at night

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Patients with chronic insomnia may have an overactive brain at night9,10

Research suggests that wake‑promoting regions of the brain remain overactive at night in chronic insomnia: an overactive wake-signalling known as hyperarousal.9,10,13

Chronic insomnia is closely associated with behavioural perpetuating factors, such as compensatory strategies against perceived sleep loss like excessive time in bed and daytime napping. Subjects may become conditioned to arousal and anxiety during an acute episode of insomnia, leading to sleep problems even after the removal of the initial stressor. Worry and rumination are unproductive thought processes associated with a level of physiological arousal incompatible with sleep initiation and maintenance.10,13 Arousal is expressed in terms of somatic, cognitive and cortical activation; the bed and sleep environment become stimuli for arousal instead of “de‑arousal”.10

Select a region of the body to reveal the associated physiological indicators of hyperarousal:13

Brain

  • Increased EEG fast frequencies during sleep
  • Increased number of arousals during REM sleep
  • Increased daytime sleep‑onset latency
  • Short sleep duration
associated with increased sensorimotor and cognitive activity
Pituitary-adrenal axis
  • Increased activity
associated with increased cortisol levels
Systemic
  • Increased metabolic rate
  • Increased body temperature
Heart
  • Increased heart rate
  • Altered heart rate variability
associated with increased activity of the autonomic nervous system
Descriptors above are based on comparisons with the general population.13

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QUVIVIQℱ mode of action (MoA)

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5-HT: serotonin; ACh: acetylcholine; ARAS: ascending reticular activating system; DA: dopamine; EEG: electroencephalogram; GABA: gamma-aminobutyric acid; GAL: galanin; HA: histamine; NA: noradrenaline; REM: rapid eye movement

QUVIVIQℱ is indicated for the treatment of adult patients with insomnia characterised by symptoms present for at least 3 months and considerable impact on daytime functioning.14

This information is intended for UK healthcare professionals.

â–ŒThis medicine is subject to additional monitoring.

Adverse events must be reported. Healthcare professionals are asked to report any suspected adverse reactions via www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in Google Play or Apple App Store. Adverse events should also be reported to ds.safety.uk@idorsia.com

References

  1. Della Monica C, Dijk D J. The external and internal factors that influence a good night’s sleep. Physiol Soc 2018; doi:10.36866/pn.113.36
  2. Saper C B, Scammell T E, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 2005;437(7063):1257-1263
  3. Philips A J K, Robinson P A. A quantitative model of sleep-wake dynamic based on the physiology of the brainstem ascending arousal system. J Biol Rhythms 2007;22(2):167-179
  4. Scammell T E, Winrow C J. Orexin receptors: pharmacology and therapeutic opportunities. Ann Rev Pharmacol Toxicol 2011;51:243-266
  5. Brisbare-Roch C, Dingemanse J et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 2007;13(2):150-155
  6. Saper C B, Chou T C, Scammell T E. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 2001;24(12):726-731
  7. Buysse D J, Germain A et al. A neurobiological model of insomnia. Drug Discov Today Dis Models 2011;8(4):129-137
  8. Riemann D, Nissen C et al. The neurobiology, investigation and treatment of chronic insomnia. Lancet Neurol 2015;14(5):547-558
  9. Nofzinger E, Buysse D J et al. Functional neuroimaging evidence for hyperarousal in insomnia. Am J Psychiatry 2004;161(11):2126-2128
  10. Riemann D, Spiegelhalder K, et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev 2010;14(1):19-31
  11. Roch C, Bergamini G et al. Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology (Berl) 2021;238:2693-2708
  12. Scammell T E, Winrow C J. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol 2011;51:243-266
  13. Morin C M, Drake C L et al. Insomnia disorder. Nat Rev Dis Primers 2015;1:15026
  14. QUVIVIQℱ Idorsia Pharmaceuticals Ltd, Summary of Product Characteristics

© NICE 2023 Daridorexant for treating long-term insomnia. Available from www.nice.org.uk/guidance/ta922. All rights reserved. Subject to Notice of rights.

NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/ publication.

UK-DA-00654 | Date of preparation: September 2025

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