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2000
Volume 20, Issue 4
  • ISSN: 1574-8855
  • E-ISSN: 2212-3903

Abstract

Background

Orexin receptor antagonists (ORA) are the emerging class of hypnotics used for the treatment of insomnia. However, from the available literature, the effect of ORA on cognitive functions is not clear yet. Therefore, the current study aimed to systematically evaluate the effect of ORA on cognitive function from available clinical studies.

Methods

The extensive literature search was conducted in various databases, including Pubmed, Embase, Cochrane Library, and clinicaltrials.gov, using suitable keywords. The quality of the included studies was evaluated using the Cochrane risk of bias tool (ROB2).

Results

We obtained a total of 450 articles from different databases. Finally, 07 articles met the inclusion criteria and were included in the current systematic review for qualitative analysis. Available literature showed conflicting results, with few studies showing no impact of ORA on cognitive function, while others reported dose-dependent adverse effects of ORA on cognitive function. The risk of bias in included studies was found to be low.

Conclusion

In conclusion, ORA is generally safe in clinical doses. However, it is important to note that there is a dose-dependent decline in cognitive function after the administration of ORA. Therefore, clinicians must be careful while prescribing ORA and adjust the dose as per the needs of the individual patients and the potential risk factors.

© 2025 Bentham Science Publishers
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2025-10-04

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References

  1. SheibaniM. ShayanM. KhalilzadehM. GhasemiM. DehpourA.R. ORA in the pathophysiology and treatment of sleep disorders and epilepsy.Neuropeptides20239910233510.1016/j.npep.2023.102335 37003137
     [Google Scholar]
  2. OkudaS. QureshiZ.P. YanagidaY. ItoC. HommaY. TokitaS. Factors associated with prescriptions for an ORA among japanese patients with insomnia: Analysis of a Nationwide Japanese Claims Database.Drugs Real World Outcomes202310227128110.1007/s40801‑023‑00356‑4 36867350
     [Google Scholar]
  3. BhaskarS. HemavathyD. PrasadS. Prevalence of chronic insomnia in adult patients and its correlation with medical comorbidities.J. Family Med. Prim. Care20165478078410.4103/2249‑4863.201153 28348990
     [Google Scholar]
  4. KhanH GargA Yasmeen Zolpidem use and risk of suicide: A systematic review and meta-analysis.Psychiatry Res.202231611477710.1016/j.psychres.2022.114777 35985088
     [Google Scholar]
  5. RamaswamyG. PremarajanK.C. KarS.S. NarayanS.K. ThekkurP. Prevalence and determinants of sleep disorders in a community in rural southern India.Natl. Med. J. India2020333132
     [Google Scholar]
  6. SeolJ. FujiiY. ParkI. Distinct effects of ORA and GABA A agonist on sleep and physical/cognitive functions after forced awakening.Proc. Natl. Acad. Sci. USA201911648243532435810.1073/pnas.1907354116 31712421
     [Google Scholar]
  7. PageM.J. McKenzieJ.E. BossuytP.M. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.BMJ202137271n7110.1136/bmj.n71 33782057
     [Google Scholar]
  8. NeylanT.C. RichardsA. MetzlerT.J. Acute cognitive effects of the hypocretin receptor antagonist ALM relative to zolpidem and PBO: A randomized clinical trial.Sleep20204310zsaa08010.1093/sleep/zsaa080 32303763
     [Google Scholar]
  9. ShigaT. HoshinoH. OchiaiH. Effects of benzodiazepine and ORA on cognitive function revealed by auditory event-related potentials.J. Psychopharmacol.202135121488149510.1177/02698811211035390 34330170
     [Google Scholar]
  10. LandryI. HallN. AlurJ. Acute Cognitive effects of the dual ORA LEM compared with SUV and zolpidem in recreational sedative users.J. Clin. Psychopharmacol.202242437438210.1097/JCP.0000000000001562 35748777
     [Google Scholar]
  11. MurphyP. KumarD. ZammitG. RosenbergR. MolineM. Safety of LEM versus PBO and zolpidem: Effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening.J. Clin. Sleep Med.202016576577310.5664/jcsm.8294 32022664
     [Google Scholar]
  12. LandryI. HallN. AluriJ. Effect of alcohol coadministration on the pharmacodynamics, pharmacokinetics, and safety of LEM: A randomized, PBO-controlled crossover study.J. Psychopharmacol.202236674575510.1177/02698811221080459 35634694
     [Google Scholar]
  13. HoeverP. De HaasS.L. DorffnerG. ChiossiE. Van GervenJ.M. DingemanseJ. Orexin receptor antagonism: An ascending multiple-dose study with ALM.J. Psychopharmacol.20122681071108010.1177/0269881112448946
     [Google Scholar]
  14. SithirungsonS. SonsuwanN. ChattipakornS.C. ChattipakornN. ShinlapawittayatornK. Functional roles of orexin in obstructive sleep apnea: From clinical observation to mechanistic insights.Sleep Med.2023101404910.1016/j.sleep.2022.10.016 36334500
     [Google Scholar]
  15. MogaveroM.P. GodosJ. GrossoG. CaraciF. FerriR. Rethinking the Role of Orexin in the Regulation of REM Sleep and Appetite.2023Available From: https://www.mdpi.com/2072-6643/15/17/3679/htm 10.3390/nu15173679
     [Google Scholar]
  16. KhazaieH. SadeghiM. KhazaieS. HirshkowitzM. SharafkhanehA. Dual ORA for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, PBO-controlled trials of SUV and LEM.Front. Psychiatry202213Dec107052210.3389/fpsyt.2022.1070522 36578296
     [Google Scholar]
  17. MuehlanC. RochC. VaillantC. DingemanseJ. The orexin story and ORA for the treatment of insomnia.J. Sleep Res.2023326e1390210.1111/jsr.13902 37086045
     [Google Scholar]
  18. HuangZ.L. UradeY. HayaishiO. The role of adenosine in the regulation of sleep.Curr. Top. Med. Chem.20111181047105710.2174/156802611795347654 21401496
     [Google Scholar]
  19. KatzmanM.A. KatzmanM.P. Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone.Brain Sci.202212215010.3390/brainsci12020150 35203914
     [Google Scholar]
  20. MirboloukB. Khakpour-TaleghaniB. RostampourM. JafariA. RohampourK. Enhanced low-gamma band power in the hippocampus and prefrontal cortex in a rat model of depression is reversed by orexin-1 receptor antagonism.IBRO Neuroscience Reports20231538639410.1016/j.ibneur.2023.11.006 38074161
     [Google Scholar]
  21. ToorB. RayL.B. PozzobonA. FogelS.M. Sleep, Orexin and Cognition.Front Neurol. Neurosci.202145385110.1159/000514960 34052810
     [Google Scholar]
  22. AkbariE. NaghdiN. MotamediF. Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition, consolidation and retrieval in Morris water maze task.Behav. Brain Res.20061731475210.1016/j.bbr.2006.05.028 16815564
     [Google Scholar]
  23. AkbariE. NaghdiN. MotamediF. The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze.Peptides200728365065610.1016/j.peptides.2006.11.002 17161886
     [Google Scholar]
  24. AkbariE. MotamediF. NaghdiN. NoorbakhshniaM. The effect of antagonization of orexin 1 receptors in CA1 and dentate gyrus regions on memory processing in passive avoidance task.Behav. Brain Res.2008187117217710.1016/j.bbr.2007.09.019 17977608
     [Google Scholar]
  25. BoschenK.E. FadelJ.R. BurkJ.A. Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, disrupts attentional performance in rats.Psychopharmacology (Berl.)2009206220521310.1007/s00213‑009‑1596‑2 19575184
     [Google Scholar]
  26. DietrichH. JenckF. Intact learning and memory in rats following treatment with the dual ORA ALM.Psychopharmacology (Berl.)2010212214515410.1007/s00213‑010‑1933‑5 20631993
     [Google Scholar]
  27. UslanerJ.M. TyeS.J. EddinsD.M. ORA differ from standard sleep drugs by promoting sleep at doses that do not disrupt cognition.Sci. Transl. Med.20135179179ra4410.1126/scitranslmed.3005213 23552372
     [Google Scholar]
  28. ZhouM. Dual ORA and Tgn-020 affect learning and memory in 8-mth-old APP/PS1 (AD) mice.Preprint2022
     [Google Scholar]
  29. ManessE.B. BlumenthalS.A. BurkJ.A. Dual orexin/hypocretin receptor antagonism attenuates attentional impairments in an NMDA receptor hypofunction model of schizophrenia.bioRxiv2023
     [Google Scholar]
  30. HoriH. Successful treatment of switching from benzodiazepine to ORA improves cognitive function in psychiatric disorders: Four case reports.Int. Clin. Psychopharmacol.202338319219410.1097/YIC.0000000000000450 36539372
     [Google Scholar]
  31. PeyronC. TigheD.K. van den PolA.N. Neurons containing hypocretin (orexin) project to multiple neuronal systems.J. Neurosci.1998182399961001510.1523/JNEUROSCI.18‑23‑09996.1998 9822755
     [Google Scholar]
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Effects of Orexin Receptor Antagonist on Cognitive Function in Adults: A Systematic Review
Curr Drug Ther 20, 581 (2025); https://doi.org/10.2174/0115748855292051240327084430
/content/journals/cdth/10.2174/0115748855292051240327084430
/content/journals/cdth/10.2174/0115748855292051240327084430
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  • Article Type:     Review Article
Keyword(s): cognition; database; hypnotics; insomnia; ORA; Orexin receptor antagonist

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