The co-occurrence of insomnia and obstructive sleep apnea (OSA), two of the most common sleep disorders, was first documented in 1973.1 Yet, clinicians and researchers alike have tended to characterize these disorders as distinct, with independent symptoms, pathways, and treatments. More recently, evidence of a bidirectional relationship between OSA and insomnia has been uncovered, spurring increased interest in the field.
In a 2016 study published in Sleep Medicine Reviews, researchers at the Adelaide Institute for Sleep Health, Flinders University, in Adelaide, Australia, coined the term COMISA (comorbid insomnia and sleep apnea) to describe these co-occurring disorders.2 COMISA appears to be more prevalent than previously thought, with 30-50% of patients diagnosed with OSA also reporting chronic insomnia. In contrast, in patients first diagnosed with insomnia, at least 30-40% have comorbid OSA. 3,4
The Impact of Comorbid Insomnia and Sleep Apnea
Both insomnia and sleep apnea are characterized by dysfunctions in sleep, mood, and social and workplace functioning. However, the co-occurrence of these disorders may lead to the exacerbation of these symptoms.5
“By definition, people with OSA and insomnia may suffer the adverse consequences associated with both conditions,” explained Danny Eckert, PhD, director, Adelaide Institute for Sleep Health at Flinders University. “This includes aggravated fatigue, sleepiness, irritability, poor mood, mental health issues such as anxiety and depression, poor concentration, and headaches,” said Dr Eckert, who has done extensive research on human sleep and respiratory physiology.
COMISA is associated with poorer cardiovascular and metabolic health, often co-occurring with cardiovascular disorders, hypertension, and diabetes.6 Patients with COMISA report an average pain intensity 20 points higher than individuals with just insomnia or OSA, indicating a link between COMISA and chronic pain.7 COMISA is also associated with suicidal ideation and an increased risk for self-harm.5
Researchers at the Adelaide Institute for Sleep Health demonstrated a 47-56% increase in the risk for all-cause mortality in patients with COMISA.5,8 “Social determinants of health play a major role in influencing health outcomes. Yet, the co-relationship between COMISA and mortality persisted after controlling for sociodemographic factors, behavioral factors, and chronic conditions, and remained consistent across diverse insomnia and OSA diagnostic criteria,” explained Dr Eckert.
A Bidirectional Relationship
Although comorbid insomnia and sleep apnea is prevalent in the general population, it’s only recently that researchers started to explore in-depth its causes and consequences, said Dr Eckert. Researchers have proposed several bidirectional causal relationships in pathophysiological mechanisms and clinical manifestations that could contribute to the development and progression of COMISA.
One proposed mechanism, from a May 2022 study published in Sleep Breath, is that OSA is a precursor and risk factor for the development of insomnia. Since patients with insomnia often misconstrue prior sleep as wakefulness, it has been hypothesized that patients with COMISA associate post-respiratory event awakening with wakefulness, resulting in a prolonged time to fall asleep through the night.9
“Another major potential cause is the presence of a ‘low arousal threshold’ endotype, whereby approximately 30% of people with sleep apnea simply wake up too easily with only minor upper airway narrowing episodes,” explained Dr Eckert. He added, “These frequent awakenings may trigger insomnia episodes and periods of wakefulness throughout the night. Insomnia and light sleep may then further worsen sleep apnea, and so the cycle continues/worsens.”
This hypothesis is supported by the fact that patients with COMISA treated with continuous positive airway pressure (CPAP) therapy experience a reduction in insomnia symptoms.2
Conversely, some researchers have suggested insomnia could develop first as a precursor for OSA. Sleep deprivation resulting from insomnia can reduce upper airway muscle tone, leading to reduced minimum oxygen saturation in patients with mild OSA. However, this hypothesis is not supported by empirical evidence, according to a 2018 study published in the Journal of Clinical Sleep Medicine.10
A third potential linkage between OSA and insomnia implicates the hypothalamic-pituitary-adrenal (HPA) axis. HPA activation via stress can lead to sleep fragmentation and insomnia. Concurrently, OSA-associated respiratory events can also autonomically activate HPA. HPA activation, in turn, results in metabolic and cardiovascular dysfunction, which could explain the comorbidities associated with COMISA.3
Clinical Implications of Insomnia and OSA
Although the relationship between insomnia and OSA has not been fully elucidated, diagnostic, therapeutic, and preventative implications of this relationship cannot be ignored. While early diagnosis is vital to treatment success, the shared symptoms of insomnia and OSA can complicate the diagnosis and measurement of each disorder. Additional research is necessary to define effective diagnostic criteria for COMISA, but clinicians should consider enriching their evaluation with complete patient medical histories, physical examinations, sleep diaries, polysomnography, and actigraphy.11
The multifactorial pathology of COMISA also influences treatment approaches for these sleep disorders. “Comorbidities are common in COMISA and thus, ideally, any treatment management approach is tailored to the individual to account for comorbidities,” Dr Eckert advised.
Cognitive behavioral therapy for insomnia (CBTi), the first-line treatment for insomnia, also appears to be effective in the treatment of COMISA. COMISA-associated complications such as depression, anxiety, and stress do not dampen the effectiveness of CBTi.12
CPAP therapy is the most effective treatment for OSA. However, many studies have suggested that insomnia can negatively impact CPAP use among patients. “Thus, treating insomnia first (or in parallel to sleep apnea) can reduce the severity of sleep apnea,”13 said Dr Eckert. “When insomnia is treated first, it improves patient compliance with CPAP therapy.”14
A combinatorial approach in which CBTi is commenced prior to CPAP therapy has also shown greater potential for improving daytime functioning and sleep compared to individual therapies.15 Non-CPAP-based therapies, including oral appliance devices, upper airway surgery, and nasal dilator strips, have also been explored for COMISA treatment. However, further research is warranted before the efficacy of these techniques can be established.6
Given the significant impact of COMISA on mortality and quality of life, clinicians are beginning to consider ways in which COMISA risk can be identified and mitigated.
“Awareness is step one,” said Dr Eckert. “Simple questionnaires for insomnia, such as the Insomnia Severity Index (ISI), and sleep apnea screening questionnaires, such as the OSA50 and STOP-BANG, can help identify those with a high risk for either condition alone or both.” He added, “Subsequently, healthy lifestyle measures such as a healthy diet, exercise, regular schedules, and weight loss strategies can help promote optimal sleep health and well-being. Physicians should also promptly consider onward referrals to sleep specialists if required.”
Unanswered Questions Remain
Multifaceted molecular and clinical underpinnings of insomnia and OSA appear to work in concordance, prompting debilitating complications in patients. With COMISA research only in its infancy, several questions regarding its development, multi-organ impact, night-to-night variability, treatment, and physiology remain unanswered. Nevertheless, recent evidence merits more comprehensive efforts by clinicians to investigate and diagnose the potential co-occurrence of these disorders to improve the quality of life of patients.
This article originally appeared on Neurology Advisor
- Guilleminault C, Eldridge FL, Dement WC. Insomnia with sleep apnea: a new syndrome. Science. 1973;181(4102):856-858. doi:10.1126/science.181.4102.856
- Sweetman AM, Lack LC, Catcheside PG, et al. Developing a successful treatment for co-morbid insomnia and sleep apnoea. Sleep Medicine Reviews. Published online May 6, 2016. doi:10.1016/j.smrv.2016.04.004
- Sweetman A, Lack L, McEvoy RD, et al. Bi-directional relationships between co-morbid insomnia and sleep apnea (COMISA). Sleep Medicine Reviews. Published online June 23, 2021. doi:10.1016/j.smrv.2021.101519
- 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 Medicine Reviews. Published online February 10, 2019. doi:10.1016/j.smrv.2019.01.004
- Sweetman A, Lechat B, Appleton S, Reynolds A, Adams R, Melaku YA. Association of co-morbid insomnia and sleep apnoea symptoms with all-cause mortality: analysis of the NHANES 2005-2008 data. Sleep Epidemiology. 2022;2:100043. doi:10.1016/j.sleepe.2022.100043
- Ragnoli B, Pochetti P, Raie A, Malerba M. Comorbid Insomnia and Obstructive Sleep Apnea (COMISA): current concepts of patient management. Int J Environ Res Public Health. Published online September 1, 2021. doi:10.3390/ijerph18179248
- Mundt J, Eisenschenk S, Robinson M. Severity and likelihood of chronic pain in individuals with obstructive sleep apnea and insomnia. The Journal of Pain. Published online April 1, 2017. doi:10.1016/j.jpain.2017.02.246
- 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. NSS. Published online October 13, 2022. doi:10.2147/NSS.S379252
- Wallace DM, Sweetman A. Comorbid sleep apnea, post-traumatic stress disorder, and insomnia: underlying mechanisms and treatment implications — a commentary on El Solh et al.’s Impact of low arousal threshold on treatment of obstructive sleep apnea in patients with post-traumatic stress disorder. Sleep Breath. Published online May 30, 2022. doi:10.1007/s11325-020-02107-z
- Cori JM, Nicholas CL, Avraam J, et al. The effects of experimental sleep fragmentation and sleep deprivation on the response of the genioglossus muscle to inspiratory resistive loads. Journal of Clinical Sleep Medicine. Published online May 15, 2018. doi:10.5664/jcsm.7090
- Janssen HCJP, Venekamp LN, Peeters GAM, Pijpers A, Pevernagie DAA. Management of insomnia in sleep disordered breathing. Eur Respir Rev. Published online September 30, 2019. doi:10.1183/16000617.0080-2019
- Sweetman A, Lack L, McEvoy RD, et al. Effect of depression, anxiety, and stress symptoms on response to cognitive behavioral therapy for insomnia in patients with comorbid insomnia and sleep apnea: a randomized controlled trial. Journal of Clinical Sleep Medicine. Published online March 1, 2021. doi:10.5664/jcsm.8944
- Sweetman A, Lack L, McEvoy RD, et al. Cognitive behavioural therapy for insomnia reduces sleep apnoea severity: a randomised controlled trial. ERJ Open Research. Published online March 17, 2020. doi:10.1183/23120541.00161-2020
- 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. Published online August 19, 2019. doi:10.1093/sleep/zsz178
- Tu AY, Crawford MR, Dawson SC, et al. CBT-I and CPAP in Comorbid Insomnia and Sleep Apnea: Effects on Daytime Functioning. Sleep. Published online May 27, 2020. doi:10.1093/sleep/zsaa056.651