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Semin Respir Crit Care Med
DOI: 10.1055/a-2591-5664
Review Article

Comorbid Insomnia and Sleep Apnea: From Research to Clinical Practice

Miguel Meira e Cruz
1   Sleep Unit, Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Lisbon Faculty of Medicine and Centro Europeu do Sono, Lisbon, Portugal
2   Adelaide Institute for Sleep Health, Flinders University, Bedford Park, SA, Australia
,
Alexander Sweetman
1   Sleep Unit, Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Lisbon Faculty of Medicine and Centro Europeu do Sono, Lisbon, Portugal
2   Adelaide Institute for Sleep Health, Flinders University, Bedford Park, SA, Australia
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Funding None.
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Abstract

Comorbid insomnia and sleep apnea (COMISA) represents a highly prevalent and clinically significant overlap between the two most common sleep disorders: insomnia and obstructive sleep apnea (OSA). COMISA is associated with greater impairment in sleep, daytime functioning, and physical and mental health compared with insomnia or OSA alone. Despite its prevalence, COMISA has historically been underrecognized, partially due to the conflicting symptoms of insomnia (e.g., hyperarousal and sleeplessness) and OSA (e.g., sleep fragmentation and excessive daytime sleepiness). Recent research highlights that COMISA is not merely the coexistence of insomnia and OSA but may involve unique pathophysiological interactions and clinical phenotypes. This review explores the epidemiology, mechanisms, and clinical manifestations of COMISA. We examine insomnia as a potential extension of OSA, where repeated apneic events lead to conditioned hyperarousal, as well as OSA as an extension of chronic insomnia through mechanisms such as autonomic dysregulation and respiratory instability. Furthermore, we consider COMISA as a distinct entity, characterized by bidirectional interactions between the two conditions that exacerbate their clinical and physiological burden. Key challenges in diagnosing COMISA are discussed, including overlapping symptoms and limitations in current assessment tools. Emerging evidence suggests that COMISA is associated with increased cardiovascular and metabolic risks, greater mental health burden, and reduced treatment adherence to positive airway pressure (PAP) therapy. Advances in tailored therapeutic approaches, including combined cognitive–behavioral therapy for insomnia and OSA management strategies, are highlighted as promising avenues to improve outcomes. Understanding COMISA as a multidimensional condition with diverse phenotypes and mechanisms underscores the need for integrated diagnostic frameworks and personalized treatment strategies to optimize patient care. Further research into its unique features and long-term consequences is critical to advancing clinical practice in sleep and respiratory medicine.

Keywords

comorbid insomnia and sleep apnea (COMISA) - obstructive sleep apnea (OSA) - insomnia - sleep disorders - cardiometabolic risk


Publication History

Accepted Manuscript online:
21 April 2025

Article published online:
30 May 2025

© 2025. Thieme. All rights reserved.

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  • References

  • 1 American Academy of Sleep Medicine.. International Classification of Sleep Disorders. 3rd ed. Westchester, IL: American Academy of Sleep Medicine; 2014
    Search in Google Scholar
  • 2 Sweetman AM, Lack LC, Catcheside PG. et al. Developing a successful treatment for co-morbid insomnia and sleep apnoea. Sleep Med Rev 2017; 33: 28-38
    PubMedSearch in Google Scholar
  • 3 Guilleminault C, Eldridge FL, Dement WC. Insomnia with sleep apnea: a new syndrome. Science 1973; 181 (4102) 856-858
    PubMedSearch in Google Scholar
  • 4 Lichstein KL, Riedel BW, Lester KW, Aguillard RN. Occult sleep apnea in a recruited sample of older adults with insomnia. J Consult Clin Psychol 1999; 67 (03) 405-410
    PubMedSearch in Google Scholar
  • 5 Krakow B, Melendrez D, Ferreira E. et al. Prevalence of insomnia symptoms in patients with sleep-disordered breathing. Chest 2001; 120 (06) 1923-1929
    CrossrefPubMedSearch in Google Scholar
  • 6 Sweetman A, Lack L, Bastien C. Co-morbid insomnia and sleep apnea (COMISA): prevalence, consequences, methodological considerations, and recent randomized controlled trials. Brain Sci 2019; 9 (12) 371
    CrossrefPubMedSearch in Google Scholar
  • 7 Luyster FS, Buysse DJ, Strollo Jr PJ. Comorbid insomnia and obstructive sleep apnea: challenges for clinical practice and research. J Clin Sleep Med 2010; 6 (02) 196-204
    CrossrefPubMedSearch in Google Scholar
  • 8 Bjorvatn B, Berge T, Lehmann S, Pallesen S, Saxvig IW. No effect of a self-help book for insomnia in patients with obstructive sleep apnea and comorbid chronic insomnia—a randomized controlled trial. Front Psychol 2018; 9: 2413
    PubMedSearch in Google Scholar
  • 9 Alessi CA, Fung CH, Dzierzewski JM. et al. Randomized controlled trial of an integrated approach to treating insomnia and improving the use of positive airway pressure therapy in veterans with comorbid insomnia disorder and obstructive sleep apnea. Sleep 2021; 44 (04) zsaa235
    PubMedSearch in Google Scholar
  • 10 Sweetman A, Lack L, Catcheside PG. et al. Cognitive and behavioral therapy for insomnia increases the use of continuous positive airway pressure therapy in obstructive sleep apnea participants with comorbid insomnia: a randomized clinical trial. Sleep 2019; 42 (12) zsz178
    CrossrefPubMedSearch in Google Scholar
  • 11 Ong JC, Crawford MR, Dawson SC. et al. A randomized controlled trial of CBT-I and PAP for obstructive sleep apnea and comorbid insomnia: main outcomes from the MATRICS study. Sleep 2020; 43 (09) zsaa041
    PubMedSearch in Google Scholar
  • 12 Lechat B, Appleton S, Melaku YA. et al. The association of co-morbid insomnia and sleep apnea with prevalent cardiovascular disease and incident cardiovascular events. J Sleep Res 2022; 31 (05) e13563
    PubMedSearch in Google Scholar
  • 13 Sweetman A, Lechat B, Appleton S, Reynolds A, Adams R, Melaku Y. Association of co-morbid insomnia and sleep apnoea symptoms with all-cause mortality: analysis of the NHANES 2005–2008 data. Sleep Epidemiol 2022; 2: 100043
    PubMedSearch in Google Scholar
  • 14 Bonsignore MR, Mazzuca E, Baiamonte P, Bouckaert B, Verbeke W, Pevernagie DA. REM sleep obstructive sleep apnoea. Eur Respir Rev 2024; 33 (171) 230166
    PubMedSearch in Google Scholar
  • 15 Sweetman A, Lack L, McEvoy RD. et al. Bi-directional relationships between co-morbid insomnia and sleep apnea (COMISA). Sleep Med Rev 2021; 60: 101519
    CrossrefPubMedSearch in Google Scholar
  • 16 Papatriantafyllou E, Efthymiou D, Zoumbaneas E, Popescu CA, Vassilopoulou E. Sleep deprivation: effects on weight loss and weight loss maintenance. Nutrients 2022; 14 (08) 1549
    PubMedSearch in Google Scholar
  • 17 Meira E Cruz M, Kryger MH, Morin CM, Palombini L, Salles C, Gozal D. e Cruz MM. Comorbid insomnia and sleep apnea: mechanisms and implications of an underrecognized and misinterpreted sleep disorder. Sleep Med 2021; 84: 283-288
    PubMedSearch in Google Scholar
  • 18 Maniaci A, Lavalle S, Parisi FM. et al. Impact of obstructive sleep apnea and sympathetic nervous system on cardiac health: a comprehensive review. J Cardiovasc Dev Dis 2024; 11 (07) 204
    PubMedSearch in Google Scholar
  • 19 Abbott SBG, Souza GMPR. Chemoreceptor mechanisms regulating CO2-induced arousal from sleep. J Physiol 2021; 599 (10) 2559-2571
    PubMedSearch in Google Scholar
  • 20 Ikeda K, Kawakami K, Onimaru H. et al. The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology. J Physiol Sci 2017; 67 (01) 45-62
    PubMedSearch in Google Scholar
  • 21 Sweetman A, Lack L, McEvoy RD. et al. Cognitive behavioural therapy for insomnia reduces sleep apnoea severity: a randomised controlled trial. ERJ Open Res 2020; 6 (02) 00161-2020
    PubMedSearch in Google Scholar
  • 22 Carter SG, Eckert DJ. Effects of hypnotics on obstructive sleep apnea endotypes and severity: novel insights into pathophysiology and treatment. Sleep Med Rev 2021; 58: 101492
    PubMedSearch in Google Scholar
  • 23 Sweetman A, Andronis C, Hancock K, Stocks N, Lack L, McEvoy RD. General practitioner assessment and management of insomnia in adults. Aust J Gen Pract 2023; 52 (10) 691-698
    PubMedSearch in Google Scholar
  • 24 Sweetman A, Putland S, Lack L. et al. The effect of cognitive behavioural therapy for insomnia on sedative-hypnotic use: a narrative review. Sleep Med Rev 2021; 56: 101404
    PubMedSearch in Google Scholar
  • 25 Yelov L, Reiter J, Meira E Cruz M, Gileles-Hillel A. The association of obstructive sleep apnea and behavioral insomnia in children ages 10 and under. J Clin Sleep Med 2024; 20 (02) 245-251
    PubMedSearch in Google Scholar
  • 26 Meira E Cruz M, Salles C, Seixas L, D Elia, C, Rocha I, Gozal D. Comorbid insomnia and sleep apnea in children: a preliminary explorative study. Journal of Sleep Research 2023; 32 (01) e13705
    PubMedSearch in Google Scholar
  • 27 Krakow B, Romero E, Ulibarri VA, Kikta S. Prospective assessment of nocturnal awakenings in a case series of treatment-seeking chronic insomnia patients: a pilot study of subjective and objective causes. Sleep 2012; 35 (12) 1685-1692
    PubMedSearch in Google Scholar
  • 28 Caetano Mota P, Morais Cardoso S, Drummond M, Santos AC, Almeida J, Winck JC. Prevalence of new-onset insomnia in patients with obstructive sleep apnoea syndrome treated with nocturnal ventilatory support. Rev Port Pneumol 2012; 18 (01) 15-21
    PubMedSearch in Google Scholar
  • 29 Wallace DM, Wohlgemuth WK. Predictors of insomnia severity index profiles in United States veterans with obstructive sleep apnea. J Clin Sleep Med 2019; 15 (12) 1827-1837
    PubMedSearch in Google Scholar
  • 30 Zhang Y, Ren R, Lei F. et al. Worldwide and regional prevalence rates of co-occurrence of insomnia and insomnia symptoms with obstructive sleep apnea: a systematic review and meta-analysis. Sleep Med Rev 2019; 45: 1-17
    PubMedSearch in Google Scholar
  • 31 Sweetman A, Melaku YA, Lack L. et al. Prevalence and associations of co-morbid insomnia and sleep apnoea in an Australian population-based sample. Sleep Med 2021; 82: 9-17
    PubMedSearch in Google Scholar
  • 32 Meira E Cruz M, Salles C, Seixas L, DElia C, Rocha I, Gozal D. Comorbid insomnia and sleep apnea in children: a preliminary explorative study. J Sleep Res 2023; 32 (01) e13705
    PubMedSearch in Google Scholar
  • 33 Lechat B, Appleton S, Melaku Y. et al. Comorbid insomnia and obstructive sleep apnoea is associated with all-cause mortality. Eur Respir J 2022; 60 (01) 2101958
    PubMedSearch in Google Scholar
  • 34 Lechat B, Loffler KA, Wallace DM. et al. All-cause mortality in people with co-occurring insomnia symptoms and sleep apnea: analysis of the Wisconsin Sleep Cohort. Nat Sci Sleep 2022; 14: 1817-1828
    PubMedSearch in Google Scholar
  • 35 Meira E Cruz M, Salles C, Gozal D. A reappraisal on the associations between sleep-disordered breathing, insomnia, and cardiometabolic risk. Am J Respir Crit Care Med 2021; 203 (12) 1583-1584
    PubMedSearch in Google Scholar
  • 36 Cruz MM, Seixas L, Santos A. et al. 480 Cardiovascular and metabolic risk in patients with suspected comorbid insomnia and obstructive sleep apnea (COMISA). Sleep (Basel) 2021; 44 (Suppl. 02) A189-A190
    PubMedSearch in Google Scholar
  • 37 Meira E Cruz M, Vantine F, Kryger M, Rocha I, Salles C. Cardiometabolic status in high risk pregnant women with comorbid insomnia and sleep disordered breathing: a survey based comparative study. Sleep Med 2022; 100: S111
    PubMedSearch in Google Scholar
  • 38 O'Brien L, Okun M. 0821 Comorbid insomnia and sleep disordered breathing: association with adverse pregnancy outcomes. Sleep (Basel) 2017; 40: A304
    PubMedSearch in Google Scholar
  • 39 Meira E Cruz M, Sweetman A. Insomnia, sleep apnea, and circadian misalignment as a “three-arm” contributor to anxiety and depression during pregnancy. Sleep Vigil 2021; 5 (02) 333-335
    PubMedSearch in Google Scholar
  • 40 Meira E Cruz M, Gozal D, Salles C, Rocha I, Ettlin D. e Cruz MM. Interactions between insomnia, sleep disordered breathing and cardiometabolic risk in patients complaining of pain in the orofacial region. Acta Med Port 2025; 38 (01) 37-41
    PubMedSearch in Google Scholar
  • 41 Yanagimori M, Fernandes MD, Garcia ML. et al. Respiratory arousal threshold among patients with isolated sleep apnea and with comorbid insomnia (COMISA). Sci Rep 2023; 13 (01) 7638
    PubMedSearch in Google Scholar
  • 42 Engstrøm M, Hagen K, Bjørk MH. et al. Sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study. J Headache Pain 2013; 14 (01) 12
    PubMedSearch in Google Scholar
  • 43 Kaczmarski P, Karuga FF, Szmyd B. et al. The role of inflammation, hypoxia, and opioid receptor expression in pain modulation in patients suffering from obstructive sleep apnea. Int J Mol Sci 2022; 23 (16) 9080
    PubMedSearch in Google Scholar
  • 44 Noël-Jorand MC, Bragard D, Plaghki L. Pain perception under chronic high-altitude hypoxia. Eur J Neurosci 1996; 8 (10) 2075-2079
    PubMedSearch in Google Scholar
  • 45 Hsieh CG, Martin JL. Short sleep, insomnia, and cardiovascular disease. Curr Sleep Med Rep 2019; 5 (04) 234-242
    PubMedSearch in Google Scholar
  • 46 Abdelaziz A, Hafez AH, Roshdy MR. et al. Cognitive behavioral therapy for the treatment of insomnia in patients with cardiovascular diseases: a meta-analysis with GRADE analysis. J Behav Med 2024; 47 (05) 819-827
    PubMedSearch in Google Scholar
  • 47 Torres G, de la Torre MS, Pinilla L, Barbé F. [Obstructive sleep apnea and cardiovascular risk] [Article in English, Spanish]. Clin Investig Arterioscler 2024; 36 (04) 234-242
    PubMedSearch in Google Scholar
  • 48 Fang F, Sun Z, Gao Y. et al. Effects of combined morbid insomnia and sleep apnea on long-term cardiovascular risk and all-cause mortality in elderly patients: a prospective cohort study. BMC Geriatr 2024; 24 (01) 622
    PubMedSearch in Google Scholar
  • 49 Blaszczyk B, Meira E Cruz M, Waliszewska-Prosol M. et al Sleep bruxism and sleep structure in comorbid insomnia and obstructive sleep apnea (COMISA) syndrome: a polysomnographic study. Journal of Clinical Medicine 2024; 13 (11) 3154
    PubMedSearch in Google Scholar
  • 50 Bahia C, Oliveira VM, Mignot E. et al. A preliminary report on clinical and polysomnographic features of comorbid insomnia and sleep apnea in type 1 and type 2 narcoleptic patients. Sleep Med 2024; 115 (S1): S206-S207
    PubMedSearch in Google Scholar
  • 51 Sweetman A, Lack L, Crawford M, Wallace DM. Comorbid insomnia and sleep apnea: assessment and management approaches. Sleep Med Clin 2022; 17 (04) 597-617
    CrossrefPubMedSearch in Google Scholar
  • 52 Björnsdóttir E, Janson C, Sigurdsson JF. et al. Symptoms of insomnia among patients with obstructive sleep apnea before and after two years of positive airway pressure treatment. Sleep 2013; 36 (12) 1901-1909
    PubMedSearch in Google Scholar
  • 53 Lundetræ RS, Saxvig IW, Aurlien H, Lehmann S, Bjorvatn B. Effect of continuous positive airway pressure on symptoms and prevalence of insomnia in patients with obstructive sleep apnea: a longitudinal study. Front Psychol 2021; 12: 691495
    PubMedSearch in Google Scholar
  • 54 Glidewell RN, Renn BN, Roby E, Orr WC. Predictors and patterns of insomnia symptoms in OSA before and after PAP therapy. Sleep Med 2014; 15 (08) 899-905
    PubMedSearch in Google Scholar
  • 55 Ou Y-H, Colpani JT, Cheong CS. et al. Mandibular advancement vs CPAP for blood pressure reduction in patients with obstructive sleep apnea. J Am Coll Cardiol 2024; 83 (18) 1760-1772
    CrossrefPubMedSearch in Google Scholar
  • 56 Manetta IP, Duarte BB, Nucci LB, Enes CC. Relationship between OSA pathophysiological phenotypes and treatment response to mandibular advancement devices: a pilot study. J Clin Sleep Med 2024; 20 (08) 1321-1330
    PubMedSearch in Google Scholar
  • 57 Giannasi L, Oliveira L, Machado M. et al. Effective treatment with mandibular advancement devices in comorbid insomnia and sleep apnea: a two-step study on clinical, polysomnographic, and cardiovascular risk. Sleep Sci 2023; 16 (S 01) 001-070
    PubMedSearch in Google Scholar
  • 58 Meira e Cruz M, Guilleminault C, Gozal D, Bruni O, Pirelli P. Rapid maxillary expansion in COMISA: preliminary observations from a 12-year follow-up. Sleep (Basel) 2025; 48 (03) zsae306
    PubMedSearch in Google Scholar
  • 59 Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med 2008; 4 (05) 487-504
    CrossrefPubMedSearch in Google Scholar
  • 60 Edinger JD, Arnedt JT, Bertisch SM. et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med 2021; 17 (02) 263-298
    CrossrefPubMedSearch in Google Scholar
  • 61 Ree M, Junge M, Cunnington D. Australasian Sleep Association position statement regarding the use of psychological/behavioral treatments in the management of insomnia in adults. Sleep Med 2017; 36 (Suppl. 01) S43-S47
    CrossrefPubMedSearch in Google Scholar
  • 62 van der Zweerde T, Bisdounis L, Kyle SD, Lancee J, van Straten A. Cognitive behavioral therapy for insomnia: a meta-analysis of long-term effects in controlled studies. Sleep Med Rev 2019; 48: 101208
    CrossrefPubMedSearch in Google Scholar
  • 63 Buysse DJ, Germain A, Moul DE. et al. Efficacy of brief behavioral treatment for chronic insomnia in older adults. Arch Intern Med 2011; 171 (10) 887-895
    CrossrefPubMedSearch in Google Scholar
  • 64 Arnedt JT, Conroy DA, Mooney A, Furgal A, Sen A, Eisenberg D. Telemedicine versus face-to-face delivery of cognitive behavioral therapy for insomnia: a randomized controlled non-inferiority trial. Sleep (Basel) 2021; 44 (01) zsaa136
    PubMedSearch in Google Scholar
  • 65 Koffel EA, Koffel JB, Gehrman PR. A meta-analysis of group cognitive behavioral therapy for insomnia. Sleep Med Rev 2015; 19: 6-16
    CrossrefPubMedSearch in Google Scholar
  • 66 Bjorvatn B, Fiske E, Pallesen S. A self-help book is better than sleep hygiene advice for insomnia: a randomized controlled comparative study. Scand J Psychol 2011; 52 (06) 580-585
    PubMedSearch in Google Scholar
  • 67 Sweetman A, Reynolds C, Richardson C. Digital cognitive behavioural therapy for insomnia versus digital sleep education control in an Australian community-based sample: a randomised controlled trial. Intern Med J 2024; 54 (11) 1838-1848
    PubMedSearch in Google Scholar
  • 68 Sweetman A, Farrell S, Wallace DM, Crawford M. The effect of cognitive behavioural therapy for insomnia in people with comorbid insomnia and sleep apnoea: a systematic review and meta-analysis. J Sleep Res 2023; 32 (06) e13847
    PubMedSearch in Google Scholar
  • 69 Sweetman A, McEvoy R, Smith S. et al. The effect of cognitive and behavioral therapy for insomnia on week-to-week changes in sleepiness and sleep parameters in patients with comorbid insomnia and sleep apnea: a randomized controlled trial. Sleep (Basel) 2020; 43 (07) zsaa002
    PubMedSearch in Google Scholar
  • 70 Turner AD, Ong JC, Jones AL, Tu A, Salanitro M, Crawford MR. Neurocognitive functioning in comorbid insomnia and sleep apnea patients is better after positive airway pressure therapy, but worse after cognitive behavioral therapy for insomnia: exploratory analysis of cognitive outcomes from the Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea study. Sleep 2023; 46 (08) zsad128
    PubMedSearch in Google Scholar
  • 71 Sweetman A, Reynolds C, Lack L. et al. Effect of high-risk sleep apnea on treatment-response to a tailored digital cognitive behavioral therapy for insomnia program: a quasi-experimental trial. Front Sleep 2024; 3: 1355468
    PubMedSearch in Google Scholar
  • 72 Meira E Cruz M, Brito A, Rocha I, Salles C, Kryger M, Gozal D, Sweetman A. Clinically guided digital Cognitive Behavioural Therapy for insomnia (CBTi) in patients with COMISA: a case-control pilot study with focus on mental health and cardiometabolic risk factors. Sleep Med 2024; 115: S165
    PubMedSearch in Google Scholar
  • 73 Sweetman A, Frank O, Stocks N, Mukherjee S, Lack L. General practitioner management of comorbid insomnia and sleep apnoea. Aust J Gen Pract 2023; 52 (09) 607-612
    PubMedSearch in Google Scholar