Insomnia and Obstructive Sleep Apnea.

With more than 80 distinct sleep disorders classified in the International Classification of Sleep Disorders (ICSD-21), comorbidity of sleep disorders has emerged as an important topic with clinical and research significance. In particular, obstructive sleep apnea (OSA) and insomnia are 2 sleep disorders that co-occur frequently, involve clinical features and associations that are distinct from the separate conditions, and are treatable. OSA, which affects about 10% to 20% of middle to older aged adults,2 is characterized by the repeated obstruction of the upper airway during sleep that leads to complete cessation (apnea) or reduction (hyperpnea) of airflow, occurring irrespective of continued ventilatory effort. Before termination, these events lead to a decrease in blood oxygen saturation and an associated increase in carbon dioxide levels during longer events. The termination of the apnea is often preceded by an arousal, which leads to sleep fragmentation and activation of the sympathetic nervous system. The former is hypothesized to be involved in the neurocognitive sequelae, whereas the latter leads to cardiovascular dysregulation. This process is identified as the possible cause for the daytime sleepiness and cardiovascular health and functioning problems witnessed in these individuals.3–7 Severe OSA has been linked to a 4- to 6-fold increased risk of mortality, irrespective of factors such as age, diabetes, or high cholesterol.8,9 Symptoms of insomnia include difficulty initiating and/or maintaining sleep, waking too early, and/or nonrestorative sleep. When the nocturnal symptoms are associated with significant distress or daytime dysfunction and last for at least 3 months, the condition is considered an insomnia disorder.10 As a result of evolving diagnostic criteria for insomnia, there are large variations in the cited prevalence rates of these types of sleep difficulties, ranging from around 6% to 30%.11–13 The pathophysiology of insomnia is thought to involve hyper-arousal in the form of cognitive arousal (eg, increased cognitive activity or negative tone of cognitions) and physiologic arousal (eg, elevations in core body temperature, muscle tension, and sympathetic activation).14 The most frequently cited consequences of insomnia are the reduction in quality of life and productivity, and increased risk of accidents, and absenteeism.13,15 Insomnia may also be a risk factor for various psychiatric conditions16,17 and health problems suchashyper-tension,18 type 2 diabetes,19 and even mortality after controlling for hypertension and diabetes.20 The co-occurrence of both conditions was first described in 1973 by Guilleminault and col-leagues,21 who reported on 3 individual cases who presented to the sleep laboratory for evaluation of insomnia and were subsequently investigated for sleep-disordered breathing. More recently, the comorbidity between sleep apnea and insomnia has garnered increased research and clinical interest, likely resulting from a paradigm shift in how insomnia is conceptualized. Whereas insomnia was previously considered secondary to a primary condition, a consensus statement released by the US National Institutes of Health22 regards insomnia as a distinct disorder that can also be comorbid to another condition. This conceptualization challenges the traditional assumption that insomnia is merely a symptom of another condition, and allows for a separate diagnosis of “comorbid insomnia” even in the context of another sleep disorder such as sleep apnea. Diagnosing comorbid insomnia in the context of another sleep disorder can be challenging, as there can be overlap in the complaint of sleep disturbance (eg, difficulty maintaining sleep) and daytime dysfunction (eg, daytime fatigue). Moreover, our understanding of the mechanisms involved in the comorbid relationship remains very limited. Even well-trained clinicians cannot make reliable distinctions with regard to the attribution of insomnia symptoms.23 As a response, recent recommenda-tions10,24 enable a diagnosis of an insomnia disorder without attributing the causal relationship between the symptoms and the co-occurring disorder. In the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), specifiers are used with an insomnia disorder to note the comorbid condition rather than attempting to assign causal attributions, as was the case in previous classification systems such as DSM-IV (ie, primary vs secondary insomnia). With these shifts in conceptualization and nosology, several research studies focusing on the insomnia/OSA co-morbidity have emerged. This growing body of literature is shaping our understanding of the relationship, consequences, and treatment implications of comorbid insomnia and sleep apnea. This review of the literature is organized on the basis of the progression of research on the comorbidity between insomnia and sleep apnea. First, clinical features and associations with this comorbidity are discussed, much of which has been informed by cross-sectional studies. Second, the authors discuss models of pathogenesis that have been proposed in the literature. Here, emerging data from longitudinal studies and relevant retrospective studies that are capable of examining the time course of the two disorders are highlighted. Finally, the clinical implications of this review are discussed, and suggestions are made regarding future research.