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Postgraduate Education Corner: CONTEMPORARY REVIEWS IN SLEEP MEDICINE |

Insomnia and Sleep-Related Breathing Disorders FREE TO VIEW

Emerson M. Wickwire, PhD, ABPP; Nancy A. Collop, MD, FCCP
Author and Funding Information

From the Center for Sleep Disorders (Dr Wickwire), Pulmonary Disease and Critical Care Associates, Columbia, MD; and Johns Hopkins Hospital Sleep Disorders Center, Division of Pulmonary and Critical Care (Dr Collop), Johns Hopkins School of Medicine, Baltimore, MD.

Correspondence to: Emerson M. Wickwire, PhD, ABPP, Center for Sleep Disorders, Pulmonary Disease and Critical Care Associates, 10710 Charter Dr, Ste 310, Columbia, MD 21044; e-mail: ewickwire@pulmdocs.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(6):1449-1463. doi:10.1378/chest.09-1485
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Insomnia disorder and obstructive sleep apnea are the two most common sleep disorders among adults. Historically, these conditions have been conceptualized as orthogonal, or insomnia has been considered a symptom of sleep apnea. Insomnia researchers have sought to exclude participants at risk for sleep-related breathing disorders (SRBD), and vice versa. In recent years, however, there has been a growing recognition of co-occurring insomnia disorder and SRBD and interest in the prevalence, consequences, and treatment of the two conditions when they co-occur. Although plagued by inconsistent diagnostic criteria and operational definitions, evidence from clinical and research samples consistently suggests high rates of comorbidity between the two disorders. More important, insomnia disorder and SRBD have additive negative effects. To date, only a few studies have explored the combined or sequential treatment of the conditions. Results support the importance of an integrated, interdisciplinary approach to sleep medicine. This article reviews the empirical literature to date and provides clinical recommendations as well as suggestions for future research.

In recent years, clinicians and researchers have become increasingly aware of the frequent comorbidity of insomnia disorder and sleep-related breathing disorders (SRBD) and have begun to ask important questions about the prevalence, consequences, and treatment of these disorders when they co-occur.1-3 The purpose of this review article is to explore the relationships between these two conditions. First, we briefly review the definition, epidemiology, and causes of the two disorders. We then consider the co-occurrence and consequences of insomnia disorder and SRBD in clinical, recruited, and population samples, and review recent hypotheses regarding potential shared physiologic mechanisms between the two conditions. Finally, we consider clinical issues, including assessment, diagnosis, and treatment of the two disorders when they co-occur, as well as potential interactions among treatments. We conclude with clinical recommendations and suggestions for future research, including the further development of an integrated, interdisciplinary approach to the assessment, diagnosis, and treatment of sleep disorders.

Insomnia, characterized by difficulty initiating or maintaining sleep, early morning awakening, or nonrestorative sleep, is the most common sleep complaint among adults4 and perhaps the second most frequent health complaint after pain.5 Approximately 30% of adults in the United States experience occasional transient insomnia, and prevalence estimates for chronic insomnia range from 9% to 12%.6,7 Insomnia disorder is positively correlated with age and negatively correlated with employment, education, and income.7,8 In addition, women are roughly twice as likely as men to report insomnia.7 Individuals who suffer from insomnia disorder report decreased quality of life9 and numerous health complaints, and evidence suggests they are at increased risk for cardiovascular disease and mortality.10,11 Additionally, the individual and societal costs of insomnia disorder are many and varied, ranging from treatment-related expenses to absenteeism and decreased productivity in the workplace. In a sample of > 400,000 patients, including insomniacs and matched healthy controls, Ozminkowski et al12 reported that total direct and indirect costs over a 6-month period were approximately $1,253 more for younger adults with insomnia and $1,143 greater for older adults with insomnia, relative to their noninsomniac peers. Other high-quality studies have also reported significant costs associated with insomnia disorder.13 Previous estimates of total US costs ranged from $30 to $35 billion per year14 to $92.5 to $107.5 billion per year.15

Obstructive sleep apnea (OSA) is the second most common sleep disorder and represents the most severe SRBD diagnosis, affecting 3% to 7% of adults.16 SRBD exists on a continuum from narrowing of the upper airway, to snoring, to partial obstruction (ie, hypopnea), to complete obstruction and frank cessation of airflow (ie, apnea). Detailed breathing event criteria are published elsewhere.17 Population-based studies suggest that men experience OSA at two to three times the rate of women,18 although clinical presentation can differ significantly,19 and the gender ratio among patients referred for clinical evaluation is likely to be substantially higher. Like insomnia disorder, OSA is positively correlated with age through middle adulthood, and menopause is associated with increased incidence of OSA among women. Unlike insomnia disorder, however, a plateau in OSA prevalence appears to be reached near the sixth decade of life.18 OSA is associated with numerous short-term and long-term health consequences. Acute symptoms of OSA include daytime somnolence, mood disturbance, and performance deficits including diminished executive function and cognitive and memory impairment, all of which can easily be mistaken for symptoms of other medical and psychiatric disorders. Individuals with OSA are also at increased risk of motor vehicle crashes20 and other daytime accidents. In terms of chronic effects, the picture is equally striking. In addition to decreased quality of life, OSA is positively associated with hypertension, stroke, cardiovascular death, and overall mortality.21 Like insomnia disorder, OSA results in enormous societal costs, in terms of both direct health-care expenditures and the indirect costs associated with untreated OSA.

Although the cause of chronic insomnia is unknown, the disorder is most often conceptualized within a biopsychosocial framework. Physiologic abnormalities, including increased activity in the CNS and hyperarousal of the hypothalamic-pituitary axis (HPA)22 and proinflammatory cytokines, as well as personality traits such as anxious temperament, predispose individuals to react negatively to stress, the most common precipitating cause of insomnia disorder.5 Following a period of acute sleep disturbance, maladaptive “compensatory” behaviors such as napping, spending excessive time in bed, “trying harder” to sleep, or frequent use of stimulants including caffeine, contribute to the development of a chronic condition.23 Although the pathophysiologic abnormalities associated with insomnia disorder are well known, it is notable that people with insomnia disorder attribute their insomnia to cognitive, rather than physiologic, arousal, emphasizing the mind-body nature of the sleep disturbance.24 On the same topic, Harvey25 has proposed a cognitive model of insomnia disorder, in which people with insomnia become especially attuned to perceived sleep-related threats and engage in daytime “safety behaviors” such as excessive emotional restraint (ie, inhibiting normal, appropriate emotional responses to daily life), which can exacerbate hyperarousal and lead to cognitive rumination, also prolonging insomnia.

In terms of OSA, it is unclear why some individuals develop the disease and others do not. Anatomic features such as craniofacial structures and behavioral factors have both been identified in the pathogenesis of SRBD.26 Genetic factors have also been implicated.27 In community-based studies, weight gain is among the most consistent predictors of increased prevalence of OSA.16 For example, in a longitudinal study conducted by Newman and colleagues,28 a 10% increase in body weight was associated with a 32% increase in the apnea-hypopnea index (AHI) and a sixfold risk of developing moderate or severe OSA. It is important to note, however, that a significant number of patients with SRBD are of normal weight. Behavioral factors such as drinking alcohol29 or smoking cigarettes30 have also been associated with development or worsening of SRBD, including OSA. In this light, it is notable that even in the absence of frank hypopneas and apneas, increased airway restriction (upper airway resistance syndrome [UARS]) is a distinct sleep-related breathing disorder and is associated with numerous negative health consequences.31

Co-occurrence of Insomnia Disorder and OSA

Several recent reviews have concluded that insomnia disorder and OSA are likely to coexist in sleep clinic patients.1-3 For example, a number of reports have documented high rates of insomnia complaints among patients referred for evaluation of SRBD (Table 1). All but one have relied on paper and pencil assessment of insomnia complaints. Smith et al33 required a daytime complaint and Insomnia Severity Index5 score ≥ 15, complaint duration of >6 months, and sleep-onset latency (SOL) or wake after sleep onset of ≥ 30 min as measured by polysomnography (PSG). Although OSA criteria were not presented, 39% of SRBD patients met the criteria for moderately severe insomnia. Similarly, Krell and Kapur36 found that more than one-half of patients who received a diagnosis of OSA (AHI ≥ 10) reported either delayed SOL (29.4%), increased nocturnal awakenings and time awake in bed (36.4%), or early morning awakenings (28.9%) on a self-report measure.

Table Graphic Jump Location
Table 1 —Insomnia Complaints in Patients Evaluated for Sleep-Related Breathing Disorders

AHI = apnea-hypopnea index; EMA = early morning awakenings; MI = maintenance insomnia; NOA = number of nocturnal awakenings; OI = onset insomnia; OSA = obstructive sleep apnea; PSG = polysomnogram; RDI = respiratory disturbance index; SOL = sleep-onset latency; SRBD = sleep-related breathing disorder; WASO = wake after sleep onset.

At the same time, although insomnia disorder and OSA are likely to co-occur in patients, it remains unclear whether OSA is a risk factor for insomnia disorder, or vice versa. For example, compared with patients with OSA, a significantly higher percentage (81.5%) of individuals without SRBD reported insomnia symptoms, including difficulty initiating sleep (66.7%), maintaining sleep (59.2%), and early morning awakenings (51.8%).36 Gold et al34 also reported longer sleep latencies among patients with less severe SRBD. Chung32 reported similar results in a study in which nearly one-half of 157 patients who received a diagnosis of OSA (AHI > 5) reported at least one insomnia complaint.

One reason why individuals with more severe SRBD may report less onset insomnia is that they are more likely to be sleepy during the day and at bedtime. Given this tendency, the costs associated with PSG, and the desire for diagnostically homogeneous samples, insomnia disorder researchers typically have sought to screen out participants at risk for SRBD (eg, those with high BMI and those who report snoring, choking during sleep, and so forth). Hence, the high rates of SRBD found in recruited insomnia disorder samples are somewhat startling (Table 2). Stone et al40 found that 40% of recruited older adult insomniacs had OSA (AHI > 10), whereas only 35.6% had AHI < 5. Similarly, Lichstein et al39 administered PSG to a sample of older adults with insomnia disorder. Depending on whether AHI ≥ 5 or AHI ≥ 15 was used as a diagnostic cutoff, 29% to 43% of this sample was given a diagnosis of OSA. As these results suggest, diagnostic criteria and measurement of breathing during sleep are important factors in evaluating the relation between insomnia disorder and OSA, especially because patients with insomnia disorder may also have distinct breathing disturbances.43 In the first study to use nasal cannula pressure transducer technology to measure respiration among insomnia disorder patients, Krakow et al42 administered PSG to consecutive crime victims with insomnia disorder, nightmares, and posttraumatic stress disorder, and 40 of 44 had a respiratory disturbance index ≥ 15, with 22 receiving a diagnosis of OSA and 18 a diagnosis of UARS. In another clinic-based study, > 80% of 394 postmenopausal women complaining of insomnia received a diagnosis of either OSA (67%) or UARS (15.7%).16

Table Graphic Jump Location
Table 2 —Obstructive Sleep Apnea in Insomnia Disorder

TST = total sleep time; UARS = upper airway resistance syndrome. See Table 1 for expansion of other abbreviations.

Despite the findings regarding co-occurring insomnia disorder and OSA in referred patients and recruited participants, there is a lack of high-quality epidemiologic data exploring the co-occurrence of the two disorders.44 Two studies have reported inconsistent results. In a study of 199 adults matched for age, sex, and BMI, Gooneratne et al45 found a negative association between insomnia disorder status and SRBD, with fewer insomniacs (29.3%) than noninsomniac controls (38.0%) receiving a diagnosis of OSA (AHI > 15). As is most often the case, in this study no distinctions were made between sleep-onset and sleep-maintenance insomnia complaints. Bixler and colleagues46 administered PSG to a subsample of > 1,700 community adults from a larger (N = 16,000) study and detected no significant relationship between SRBD severity and insomnia disorder.

Consequences of Comorbid Insomnia Disorder and SRBD

In terms of negative sequelae, insomnia disorder and SRBD appear to have additive negative effects. Individuals with both insomnia disorder and SRBD report worse habitual sleep than those with only SRBD.33 PSG supports this relationship, with individuals with both insomnia disorder and SRBD experiencing lower sleep efficiency and less total sleep time (TST), as well as more time awake in bed,33 compared with those with only SRBD. Similarly, in a sample matched for age, gender, and BMI and with similar SRBD profiles, Krakow et al35 observed that, compared with patients with OSA alone, patients with both insomnia disorder and OSA (AHI > 5) reported significantly longer SOL (17 min vs 65 min), shorter TST (5.6 h vs 7.2 h), and lower sleep efficiency (75% vs 92%), as measured during PSG. In describing patients with both insomnia disorder and OSA, Krakow et al42 coined the term “complex insomnia.”

Patients with both insomnia disorder and OSA also report significantly more sleepiness and demonstrate worse neurocognitive function than do patients with only SRBD.33 Kapur and colleagues47 analyzed data from 6,440 participants in the Sleep Heart Health Study, 1,149 of whom received a diagnosis of moderate-to-severe OSA. Self-reported sleepy participants were twice as likely (26.2% vs 13.1%) to report sleep-maintenance insomnia as were individuals who did not report feeling sleepy during the day.47 Because both insomnia and SRBD accounted for unique variance in sleepiness in multiple logistic regression analyses, these authors concluded that SRBD and maintenance insomnia are independent conditions. That is, insomnia is not merely a symptom of SRBD, but a distinct disease entity. Furthermore, these data suggest that individuals with both conditions are at higher risk of daytime sleepiness, and therefore associated accidents, relative to patients with SRBD alone. Another large study (N > 4,500) also found that insomnia and suspected OSA (snoring and witnessed apneas) were independently associated with daytime sleepiness,48 again suggesting distinct and co-occurring disorders rather than a symptomatic relationship between insomnia disorder and OSA. Patients with insomnia disorder and SRBD also report higher levels of mood disturbance33,42,49 and have slower psychomotor reaction times and greater functional impairment, including daytime sleepiness as measured by multiple sleep latency test, than do patients with SRBD alone.45 At least one study has found no significant differences in neuropsychologic performance between individuals with insomnia disorder and SRBD and individuals with insomnia disorder alone40; however, small sample sizes limited the power to identify differences between the groups.

Pathogenesis of Comorbid Insomnia Disorder and OSA

One explanation for these additive effects and an area for future research is a shared pathophysiology of insomnia disorder and SRBD. Roehrs and colleagues43 proposed that insomnia and OSA might represent different ends of a continuum of sleep fragmentation. Similarly, Krakow44 observed that both insomnia disorder and SRBD can lead to sleep fragmentation, which can increase collapsibility of the upper airway and lead to sleep-related respiratory events.50 Indeed, several studies have documented that sleep deprivation and/or fragmentation can increase AHI.51-53 More recently, this model was expanded by Benetó and colleagues.1 Building on increasing evidence that SRBD is associated with metabolic factors as well as systemic inflammation, these authors proposed that HPA activation and metabolic sequelae may constitute a shared mechanism between SRBD and insomnia disorder. In the Benetó et al1 model, intermittent hypoxia and sleep fragmentation due to SRBD led to increased HPA activation and metabolic sequelae, including obesity, insulin resistance, and glucose intolerance. This hyperarousal and systemic inflammation will lead to insomnia disorder in some patients. Reciprocally, insomnia disorder could worsen OSA via alterations in upper airway muscle tone or increased stage shifts during sleep. The sleep loss associated with insomnia disorder might also cause these metabolic sequelae and thereby worsen breathing. As these authors and others have noted, the extent to which insomnia and sleep loss can be equated remains unclear. Nonetheless, this hypothesis warrants further investigation and future research attention.

Similarly, Gold et al34 and others have suggested that in patients with partial pharyngeal collapse, inspiratory airflow limitation, and resulting increased α intrusion into sleeping EEG can produce a hyperarousal similar to that experienced by chronic insomniacs. If true, this “central sensitization” hypothesis might not only lend support to the model proposed by Benetó et al,1 but might also explain the delayed sleep latency among patients with mild SRBD. Chung32 similarly reported that longer sleep latency was negatively associated with daytime sleepiness, supporting the notion that increased hyperarousal might be one consequence of combined insomnia disorder and OSA. In this same study, complaints of increased nocturnal awakenings and wake after sleep onset were more common than delayed sleep onset among patients with OSA (26% and 19%, respectively, vs 6%), and were positively associated with subjective and objective daytime sleepiness.

Assessment

Whereas PSG is typically required to confirm the diagnosis of OSA, the foundation of insomnia disorder assessment is a thorough sleep history.54 At a minimum, providers should evaluate the type of insomnia complaints; the onset, frequency, and duration; sleep schedule and sleep-wake patterns on both weekdays and weekends; the sleep environment, including temperature, light, and noise; sleep behaviors such as diet, exercise, and bedroom activities; sleep-related beliefs and expectations regarding sleep; comorbid medical and psychiatric conditions; medication use, including over-the-counter sleep aids, stimulants, and caffeine; daytime functioning; and other sleep disorders. Patients should complete self-report sleep diaries and standardized questionnaires/tests as part of a comprehensive intake assessment. Actigraphy is being used with increasing frequency to provide objective data on sleep-wake patterns and can be particularly useful in identifying and treating paradoxical insomnia and circadian rhythm disorders.

Diagnosis of Chronic Insomnia

Insomnia is a broad term encompassing a number of specific classifications. The Diagnostic and Statistical Manual of Mental Disorders (fourth edition)55 diagnostic criteria for primary insomnia include difficulty initiating or maintaining sleep, or nonrestorative sleep, lasting for at least 1 month’s duration and causing clinically significant distress or daytime impairment. Although these criteria are commonly used in clinical practice, the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria for primary insomnia also stipulate that the sleep disturbance must not be due to the physiologic effects of a substance or general medical condition, and must not occur exclusively in the context of another sleep or psychiatric disorder. Distinct but similar nosologies are presented in the International Classification of Sleep Disorders (Second Edition),56 as well as in the Research Diagnostic Criteria (RDC) for Insomnia.57 (Readers are referred to a previous article in this series58 for detailed review of the International Classification of Sleep Disorders classifications of insomnia.) Only the RDC52 delineates specific diagnostic criteria for insomnia “related to” sleep apnea: (1) patient meets criteria for insomnia disorder; (2) respiratory disturbance index ≥ 5 based on nocturnal PSG; and (3) insomnia cannot be completely explained by sleep-disruptive medical or psychiatric conditions, or comorbid sleep disorders. It is worth noting here that the RDC57 report indicates that at time of publication in 2004, only five empirical papers had presented any data regarding co-occurring insomnia disorder and SRBD, and two of these were a very early case study and another early case series, using diagnostic criteria obsolete by current standards. We expect that the recent surge in publications exploring “complex insomnia” (ie, comorbid insomnia disorder-OSA) foreshadows even greater expansion as interdisciplinary understanding and integrated treatment of sleep disorders increase.

Experienced sleep clinicians are well aware that most insomnias are not “primary” and instead tend to co-occur with other medical, psychiatric, or sleep disorders. Indeed, throughout the history of sleep medicine, insomnia has most often been conceptualized as a symptom of, or “secondary” to, a primary condition such as major depressive disorder or cancer. In contrast, a recent review of the empirical evidence59 argued convincingly against this understanding. These authors reasoned that if insomnia were indeed secondary to the other condition, then the insomnia should remit with successful treatment of the primary condition. Yet Lichstein60 and others have observed that virtually no evidence supports this hypothesis. Instead, the relation between insomnia disorder and co-occurring conditions is complex and likely bidirectional, for example, as acute sleep disturbance develops into chronic insomnia disorder over time. Most important, evidence suggests that most insomnias can best be understood as comorbid, rather than secondary, conditions, which warrant independent treatment.59 For example, in a recent study of patients with comorbid insomnia disorder and major depressive disorder, administration of both escitalopram and cognitive-behavioral therapy for insomnia (CBT-I) resulted in not only reduced insomnia complaints, but also lower rates of depressive relapse, relative to treatment with escitalopram alone.61 This important finding is consistent with emerging evidence suggesting that adjunctive, independent treatment of insomnia disorder in patients undergoing treatment of other medical, psychiatric, or sleep disorders can improve not only insomnia symptoms but the primary condition as well.

In terms of diagnosis, this understanding of insomnia disorder as comorbid rather than secondary is especially important in considering co-occurring insomnia disorder and OSA. Primary insomnia is often associated with delayed sleep onset and frank nocturnal awakenings, which differ categorically from the sleep fragmentation associated with OSA. Unlike insomniacs, whose presenting complaint is often increased nocturnal awakenings or extended wake after sleep onset, patients referred for evaluation of SRBD are often unaware of their breathing difficulties and repeated awakenings and arousals during the night. Yet when insomnia disorder co-occurs with OSA, interacting symptom profiles can make accurate diagnosis challenging. For example, patients with insomnia disorder frequently present without breathing complaints even when objectively measured OSA is present.49 Conversely, daytime sleepiness from OSA can mask comorbid insomnia disorder, or difficulty maintaining sleep can easily be misattributed to SRBD when in reality sleep-maintenance insomnia disorder is present and warrants independent treatment. Similarly, in terms of clinical complaints, patients with SRBD alone are likely to present quite differently than do patients with comorbid insomnia disorder and SRBD, with patients experiencing both conditions also presenting with more depression, anxiety, stress, and pain, as well as increased alterations in PSG sleep architecture and higher rates of other comorbid sleep disorders.33,36,42,43,49 Thorough evaluation is essential. Additional suggestions are presented in Clinical Recommendations, following.

Treatment
Cognitive-Behavioral Approaches:

The effectiveness of CBT-I is well documented, and individual and metaanalytic studies support the long-term efficacy of multicomponent CBT-I relative to psychopharmacologic approaches to treating insomnia disorder.62-64 CBT-I and pharmacotherapy are equally effective in the short term, with CBT-I consistently producing significantly more durable effects. Both the National Institutes of Health4 and the American Academy of Sleep Medicine (AASM)65,66 recommend CBT-I as first-line treatment of chronic insomnia.

Indeed, CBT-I is considered the “gold standard” treatment approach for all nonacute insomnia, such as that immediately following the death of a loved one or associated with jet lag. The AASM Clinical Guideline for Evaluation and Management of Chronic Insomnia in Adults65 concludes that “psychological and behavioral interventions are effective and recommended in the treatment of chronic primary and comorbid (secondary) insomnia.” Furthermore, the AASM Guideline explains that “these treatments are effective for adults of all ages, including older adults, and chronic hypnotic users.”65 Beyond these established standards of care, patients consistently prefer CBT-I over sleeping pills.67,68 Its widespread implementation has to date been limited only by a lack of awareness and a shortage of trained specialist providers. Substantial efforts are well underway to increase the availability of CBT-I provided by appropriately trained specialists, including an increase in accredited behavioral sleep medicine fellowship training programs and the 2010 establishment of the Society for Behavioral Sleep Medicine, affiliated with the AASM and other major national sleep societies.

CBT-I is a brief, highly focused therapy designed to modify specific sleep behaviors and correct erroneous beliefs about sleep. Treatment typically takes place over two to eight weekly sessions. Although standard delivery formats for CBT-I are one-on-one or group treatment, recent evidence also supports the use of alternative and self-administered delivery formats such as via the Internet.69-71

In a comprehensive review, Morin and colleagues72 identified sleep restriction and stimulus control as the most powerful components of insomnia-treatment protocols. Sleep restriction73 uses self-report sleep diary data and seeks to restrict time in bed to roughly TST. For example, if a patient reports an average TST of 5 h during 8 h spent in bed, the prescription would be to establish a consistent wake time and then to limit time in bed to approximately the 5 h before the chosen wake time. As sleep efficiency increases, sleep opportunity is extended in 15-min increments, and the patient can go to bed earlier. Although sleep restriction is powerful, clinical experience suggests that it can be challenging to implement effectively, particularly for a nonexpert clinician. Stimulus control procedures are based on the assumption that insomnia disorder is perpetuated as the bedroom becomes a stimulus for nonsleep activities such as lying awake in bed, reading, or watching television.74-76 Patients are instructed to restrict bedroom activity to sleep and sex and to avoid spending time awake in bed by getting out of bed if unable to sleep for 15 to 20 min, and returning to bed only when sleepy.

Other common CBT-I approaches are relaxation, sleep hygiene training, and cognitive therapy. Relaxation has an extensive empirical basis, and as an isolated treatment of insomnia has been shown to decrease time awake after sleep onset and to improve subjective sleep quality77 and withdrawal from sleep medication.78 Sleep hygiene training extends beyond merely “educating” the patient about behaviors that may impact sleep negatively, such as excessive daytime napping, drinking caffeine or alcohol, smoking cigarettes, or exercising too close to bedtime, to developing a personalized treatment plan to modify sleep-interfering behaviors. Cognitive therapy25,79 is a psychologic treatment designed to identify, address, and correct salient erroneous beliefs about sleep. Recent evidence also supports the development of personalized, standardized bedtime rituals and presleep routines in the treatment of chronic insomnia.80

Additional behavioral interventions for insomnia disorder include using morning or afternoon exercise to increase homeostatic sleep drive (without exercising too close to bedtime), passive body heating 2 h before bed,81 and decreasing the impact of potential bedroom environmental distractions (eg, by wearing earplugs to reduce ambient noise). A related recommendation involves light-dark manipulation. Patients should avoid bright light as bedtime approaches, and the sleeping environment should be as dark as possible. Conversely, to help regulate the circadian clock, patients should seek exposure to bright light immediately upon awakening at a consistent waketime.

Pharmacologic Approaches:

There are two classes of Food and Drug Administration (FDA)-approved prescription medications for treatment of insomnia disorder: benzodiazepine receptor agonists, including benzodiazepine agents (estazolam, flurazepam, quazepam, temazepam, triazolam) and nonbenzodiazepines (eszopiclone, zaleplon, and zolpidem and zolpidem extended release), as well as a selective melatonin receptor agonist, ramelteon, which is approved for sleep-onset insomnia disorder. All these FDA-approved medications have demonstrated efficacy in reducing insomnia complaints, although side-effect and rebound-insomnia profiles differ. (Readers are referred elsewhere for a detailed review of insomnia pharmacotherapies.)82 It is important to note that regardless of medication prescribed, the 2008 AASM Clinical Guideline advises that “short-term hypnotic treatment should be supplemented with behavioral and cognitive therapies when possible.”65

One key component to selecting a pharmacologic agent is its duration of action. Of the older benzodiazepines, triazolam has the shortest half-life (2-4 h), whereas the others all have half-lives > 8 h. In addition to abuse potential, these medications have been associated with lingering daytime effects, likely because of the long half-lives.

A number of prescription medications are also used “off-label” to treat insomnia, including sedating antidepressants, antipsychotics, and mood stabilizers. In nonpsychiatric patients, common undesirable side effects of these medications, such as sexual dysfunction or weight gain, may present unfavorable risk-benefit ratios and are generally not recommended for insomnia complaints.

As most clinicians are aware, patients suffering from insomnia are also likely to attempt to self-medicate with a variety of substances, including herbal or homeopathic sleep aids as well as FDA-regulated over-the-counter antihistamine medications. The 2005 National Institutes of Health Chronic Insomnia State of the Science Panel reported a lack of evidence of efficacy for sleep aids in both of these categories, as well as concerns regarding the side effects and safety profiles of antihistamines.4

For patients with mild SRBD, conservative treatment approaches include weight loss and mechanical interventions such as using a “tennis ball shirt” (ie, with a tennis ball sewn into the back) to avoid sleeping in the supine position. Careful monitoring of symptoms progression is essential. However, once SRBD has progressed beyond the mild stage, most OSA patients are currently treated using one of three approaches. Customized oral mandibular repositioning devices represent the next least invasive treatment approach. These devices, which keep the airway open by pulling the lower jaw forward, have been associated with significant reductions in AHI and can be an effective treatment for mild to moderate OSA.83 The most invasive and maximally aggressive treatment options include surgical approaches such as uvulopalatopharyngoplasty. Although such approaches may be effective for certain carefully selected patients, a recent review failed to find sufficient evidence to support surgical approaches to treating OSA.84

By far the most commonly prescribed and “gold standard” treatment of OSA is continuous positive airway pressure (CPAP) therapy. CPAP consists of a mask that fits over the nose, or nose and mouth, and is connected by a hose to a small, shoebox-sized machine that generates a prescribed level of air pressure. This air pressure is delivered to the upper airway and functions as a pneumatic splint, holding the airway open and allowing the patient to breathe normally. Although CPAP is the most effective treatment currently available for OSA, patient acceptance and adherence are well-documented challenges to maximally successful treatment.85 In terms of improving adherence, a recent Cochrane review86 found that cognitive-behavioral therapy (CBT) approaches were associated with the greatest improvements in objectively measured CPAP adherence. As discussed in the Clinical Recommendations section below, appropriately trained behavioral sleep medicine or other specialists can integrate these approaches into highly effective CBT-I protocols for treatment of comorbid insomnia and SRBD.

Despite the empirically supported treatments for insomnia disorder and OSA when they occur in isolation, less in known about how to treat the two disorders when they co-occur. In the most methodologically rigorous study treating combined insomnia disorder and OSA, Guilleminault et al87 randomized 30 patients matched for age, BMI, and gender to either group CBT-I followed by surgery, or surgery followed by CBT-I. At 3 months, participants were reassessed and then assigned to the alternative treatment. Interestingly, all 15 participants in the CBT-I group perceived some residual daytime symptoms and elected to undergo surgery. Conversely, five individuals who underwent surgery first reported full improvement at 3-month follow-up and declined to participate in CBT-I. Overall, participants in both groups experienced significant benefit from both treatments. In evaluating treatment order effects, the authors reported a slight benefit for surgery followed by CBT-I. This study is notable for its randomized, crossover design and quantification of flow-limited breaths. However, it is limited by its small sample sizes and potential confounds of group randomized treatment.88 Furthermore, surgery is not considered a first-line treatment of SRBD.

In an earlier study of postmenopausal women with insomnia disorder, Guilleminault and colleagues89 separated participants into those without SRBD and those with UARS. No participants met diagnostic criteria for OSA. Participants with UARS were randomized to receive either treatment of SRBD (CPAP or turbinectomy) or CBT-I. Individuals with no SRBD were assigned to CBT-I or to a wait-list control condition that included sleep hygiene education. Although no treatment was associated with decreases in sleepiness, all groups reported significantly higher sleep quality and demonstrated decreased SOL and wake after sleep onset as measured by PSG. Participants in both CBT-I groups demonstrated improved SOL and TST as measured by PSG, relative to other conditions. Conversely, only groups assigned to treatment of SRBD showed improvement in fatigue and arousal at 6-month follow-up. Although this study did not include a combined treatment package, the differential improvements from SRBD and insomnia treatments suggest that a combined approach may be superior when treating individuals with insomnia disorder and even mild SRBD.

Clinical experience and emerging data consistently suggest that treating both insomnia disorder and SRBD improves clinical outcomes. Krakow and colleagues90 administered PSG to patients who reported refractory daytime symptoms even after treatment of insomnia. Nineteen patients were subsequently prescribed CPAP for SRBD. Relative to baseline PSG, CPAP was associated with shorter latency to sleep, fewer sleep-wake transitions, and increased rapid eye movement sleep. In a study of trauma survivors who had been given a diagnosis of insomnia disorder and OSA,90 participants were treated with CBT-I and all reported subjective decreases in insomnia severity and sleep-related interference in daily living. Individuals who continued to report symptoms of insomnia disorder were prescribed CPAP or an oral mandibular repositioning device, with one participant undergoing turbinectomy. At 3-month follow-up, 88% of participants treated for SRBD scored in the nonclinical range on measures of insomnia severity. Although subjects with poor adherence to SRBD or oral appliance were excluded from these analyses, the findings suggest that patients treated for insomnia disorder who remain symptomatic may benefit from evaluation and treatment of SRBD.90 In a study of normal-weight sleep-maintenance insomniacs reporting symptoms of SRBD, participants were randomly assigned to 4 weeks using nasal dilator strips or to a clinician-contact educational control condition. Participants in the dilator strip group reported decreased insomnia severity, less sleepiness-related interference, and fewer diary symptoms of SRBD, as well as improved sleep quality and quality of life, at 1-month follow-up.91

A final consideration in terms of treating comorbid insomnia disorder and OSA is the interaction of treatments targeting the two conditions. For example, untreated insomnia disorder may compromise clinical outcomes in patients treated for OSA. Only insomnia complaints differentiated treatment responders from nonresponders in a study of 188 SRBD patients treated with an oral mandibular repositioning device,92 and complaints of sleep-maintenance insomnia at baseline have recently been associated with poorer CPAP adherence at clinic follow-up.38 It is also possible that CPAP may worsen insomnia in predisposed patients, perhaps by conditioning the bed to be associated with anxiety regarding having to wear the CPAP mask. Fortunately, there is reason to believe that both complaints can be addressed simultaneously to improve clinical outcomes. Clinical experience suggests that CBT for CPAP adherence can be integrated effectively with CBT-I.93 In terms of pharmacologic approaches, evidence suggests that hypnotic sleep aids can lead to improved sleep during titration and subsequent CPAP adherence among nonselected patients,94-96 although at least one study has reported no treatment effect.97 Recent double-blind, randomized controlled trials among nonselected patients found that 3 mg eszopiclone administered during CPAP titration96 and first 14 days of use98 were associated with improved CPAP adherence 6 weeks later. Future research should evaluate systematically the optimal approaches to integrating CBT-I and CBT for CPAP, as well as the effect of short-term hypnotic use and CBT-I to improve CPAP adherence among patients with chronic insomnia.

In terms of drug effects on respiration, a number of placebo-controlled studies have evaluated the effects of sleep aids on breathing. Overall, newer nonbenzodiazepine agents do not appear to impact breathing significantly during sleep, with negligible changes in AHI or oxygen saturation levels.99-101 However, benzodiazepines, including diazepam and midazolam, have been shown to preferentially reduce upper airway muscle tone more than diaphragmatic muscle tone,102-104 and this imbalance is thought to worsen OSA. Benzodiazepines also raise the arousal threshold, so patients may have longer events prior to arousing from sleep. Finally, these medications are also likely to reduce hypoxic and hypercapnic ventilatory responses. The older benzodiazepine agents, which, except for triazolam, have much longer duration of action than the newer hypnotics, have been associated with more significant changes in AHI and oxygen saturation as well as daytime effects, likely because of the longer drug half-lives. Given the frequent occurrence of occult SRBD in patients presenting with insomnia complaints, providers are urged to use caution when prescribing medications that may worsen undetected SRBD.

Providing clinical recommendations regarding the co-occurrence of insomnia disorder and SRBD is challenging, controversial, and not supported by large clinical trials. Nonetheless, it is clear that a substantial number of patients experience insomnia disorder and OSA simultaneously, that patients treated for both conditions show the greatest improvement, and that sleep medicine patients will benefit from improved clinical care.

  • Standard practice should be to screen clinically for both SRBD symptoms and insomnia complaints. At a minimum, snoring and witnessed apneas should be inquired about, as well as difficulty initiating and maintaining sleep. Clinicians should keep in mind that patients with comorbid insomnia disorder and SRBD may present atypically, without common symptoms such as loud snoring or low oxygen desaturations.

  • It is especially important to assess patients’ subjective sleep quality and to screen for daytime symptoms of nonrestorative sleep, such as sleepiness or fatigue, lethargy, anhedonia, decreases in motivation, mood disturbance, or anxiety. Although these symptoms can be primary complaints associated with either insomnia disorder or OSA, they are more common in patients with combined insomnia disorder and OSA and can also be subtle indications of either undetected insomnia disorder or occult OSA.

  • When evaluating patients referred for suspected SRBD, keep in mind that one-third to over one-half present with comorbid insomnia complaints and may benefit from adjunctive insomnia evaluation and treatment. Comprehensive assessment is essential. In our interdisciplinary practices, this involves screening patients referred for evaluation of SRBD for insomnia complaints, and referral to behavioral sleep medicine for CBT-I.

  • Similarly, patients presenting with complaints of difficulty initiating or maintaining sleep are unlikely to be aware of breathing disturbances during sleep. Because both insomnia disorder and OSA increase with age and remain largely undiagnosed among these populations, older adults in general, and postmenopausal women in particular, may be at particular risk for occult OSA.

  • Be mindful of treatment context and the lack of patient awareness regarding sleep disorders, as well as the potential impact of social desirability on patient responses. Clinical experience suggests that many patients hold negative stereotypes about sleep-related breathing disorders and may incorrectly ascribe their symptoms to insomnia, when in reality, breathing or other factors may underlie or contribute to patient complaints. Conversely, patients may hold stereotypes about behavioral intervention for insomnia disorder or CPAP acceptance and adherence, which should be normalized as early in the evaluative process as possible.

  • The AASM guidelines do not recommend use of PSG for routine evaluation of insomnia disorder105 unless there is a suspected occult sleep disorder (other than insomnia) or unless the patient has failed previous behavioral or pharmacologic treatment of insomnia disorder. However, the practice parameters note that evidence is lacking regarding the diagnostic usefulness of PSG in insomnia disorder and were published prior to recent studies demonstrating high rates of co-occurring insomnia disorder and OSA. Providers bear ultimate responsibility for providing the best care to their patients. Patients presenting with primary complaints of insomnia may also have occult OSA, and providers should consider clinical presentation and risk factors thoroughly.

  • Although there are clear guidelines for the treatment of SRBD and of insomnia disorder, there is a lack of understanding about how to apply these evidence-based treatments in the context of the disorders occurring simultaneously. Clinical judgment should guide this process, attending to patient perception of disease and readiness for potentially demanding treatment such as CBT-I or CPAP. We recommend thoroughly educating patients regarding co-existing sleep disorders and treatment options, keeping in mind that (1) many patients prefer nonpharmacologic treatment options when available and (2) CBT-I and CBT for CPAP adherence can be integrated to enhance continuity of care and maximize patient benefit. Regardless of treatment approach, close monitoring of patient progress is essential.

  • Patients reporting extended SOL, wake after sleep onset, or early morning awakening (ie, ≥ 30 min) with daytime complaint should be referred to an expert in insomnia disorder and/or behavioral sleep medicine. In situations in which such referral is impractical or impossible, symptoms should be monitored carefully. At a minimum, patients can be referred to insomnia self-help treatments.106 However, providers unfamiliar with delivering CBT are cautioned that sleep hygiene, particularly when instructions are distributed as a handout or pamphlet, has no demonstrated efficacy as a monotherapy for chronic insomnia. Furthermore, clinical experience suggests that patients often become even more discouraged regarding their chances for improvement following unsuccessful efforts to improve sleep based on sleep hygiene handouts. If handouts alone changed behavior, anyone could be a concert pianist. In our practices, patients are commonly treated for insomnia via behavioral sleep medicine (ie, CBT-I) and OSA via medical therapies (ie, CPAP) simultaneously. Although the number of behavioral sleep medicine providers is rapidly expanding, growing demand currently far exceeds available supply,107 and this approach is not yet feasible in all sleep medicine centers. Nonetheless, this approach combines current “gold standard” treatments for insomnia disorder and OSA, and patients report greatly appreciating this full-service, comprehensive sleep care. For commercial sleep medicine centers, provision of comprehensive sleep health services is likely to become a distinct marketplace advantage, if not a necessity, as patients and referring providers become increasingly aware of the complex interaction of sleep disorders and symptoms and demand the most effective treatments available.

  • Although treating patients experiencing both insomnia and difficulty adhering to CPAP can be challenging, in our practices behavioral sleep medicine specialists routinely incorporate CBT for CPAP108 into highly effective CBT-I treatment protocols. This process is aided by identifying patient-specific psychologic factors likely to interfere with adjustment to CPAP, including insomnia complaints. As part of routine clinical practice, patients receiving a diagnosis of OSA are assessed in a number of domains related to CPAP adherence, such as attitudes and beliefs regarding OSA and CPAP, perceived costs and benefits of CPAP use, self-efficacy to use CPAP, daytime functioning, subjective distress, and so forth. (See, for example, Wickwire85 for a review of modifiable factors known to impact CPAP use.) The results of this brief behavioral sleep medicine evaluation are used to guide OSA treatment planning. When barriers likely to interfere with medical (ie, CPAP) treatment are identified, additional intervention might include CBT for CPAP, or other follow-up recommendations on a case-by-case basis. Because the likelihood of engaging in CPAP is established as early as titration and psychologic variables measured pretitration can classify with high accuracy patients likely to fail at CPAP,109 we conduct this evaluation as early as possible in the treatment process, so that additional support or CBT for CPAP can be provided as needed. Careful patient monitoring is essential.

  • Clinicians have long known that alcohol is also commonly used as a sleep aid. Although alcohol induces slow-wave sleep, rapid eye movement decreases sleep latency and rebound occurs as the alcohol wears off, and patients are likely to experience arousals and awakenings during the night.110 A respiratory depressant even below the “legal blood alcohol concentration,”111 alcohol suppresses the arousal response112 and is known to worsen breathing during sleep, inducing apnea in susceptible individuals and increasing disease severity in OSA patients.29,112,113 OSA patients should be cautioned against drinking alcohol close to bedtime. Although more study is needed,114 alcohol does not appear to affect CPAP’s efficacy.

  • Many drugs, especially drugs that depress the CNS, such as sedatives, narcotics, and hypnotics commonly prescribed for insomnia disorder, can negatively affect breathing during sleep. Use of these medications should be monitored, and they should be prescribed with caution. Benzodiazepines and opioids should be avoided in patients with diagnosed or suspected SRBD unless they are being used in conjunction with CPAP.

A recent case report93 described an older man who attributed most of his daytime symptoms, including sleepiness, to insomnia. He was reluctant to accept the diagnosis of OSA and experienced difficulty acclimating to the CPAP machine. After thorough psychoeducation regarding his two distinct but concurrent disorders, he was treated with the combined approach that we recommend when patients have insomnia disorder and OSA. A motivationally enhanced CBT for CPAP adherence108 was initiated, followed by CBT-I. The primary factors in developing this intervention plan were disease severity and treatment acceptability. Beginning the process with CPAP adherence emphasized to the patient the severity of his SRBD and also allowed more time to manage his progression with CPAP. Moving quickly into CBT-I was consistent with the patient’s perception of his disease and also provided ample opportunity to positively reinforce compliance with the behavior changes required by CBT-I. This kind of “give and take” is often required when treating combined insomnia disorder and SRBD.

Clinicians and researchers have become increasingly aware of the frequent co-occurrence and additive negative consequences of insomnia disorder and SRBD. Extant literature lacks consistent assessment protocols and diagnostic criteria, and there remains a paucity of systematic evaluation regarding the relationship between the two disorders. More thorough evaluation of the comorbidity and consequences of the two disorders in population and clinical samples is required. Nonetheless, it is clear that many patients present with co-occurring insomnia disorder and OSA. Furthermore, clinical experience and emerging empirical data suggest that the best treatment outcomes are obtained when patients are treated for both independent conditions. Importantly, the most effective and the gold standard treatment for OSA and insomnia disorder (ie, CPAP and CBT-I, respectively) can effectively be administered concurrently by an integrated, interdisciplinary treatment team.

As others have noted,44 sleep medicine has been plagued by an artificial body-mind distinction, with many OSA specialists having been trained in pulmonary medicine and many insomnia and behavioral sleep medicine experts having backgrounds in psychology or psychiatry. Each lacks understanding of the other and, as a result, conceptualizes sleep disorders (and sleep disorder patients) through an artificially and harmfully narrow lens. These gaps and lack of interdisciplinary appreciation have undoubtedly contributed to the belated recognition of, and lack of insight into, the frequent co-occurrence of insomnia disorder and OSA, and the formulation of strategies required for optimal treatment. In addition and more important, there is little doubt that patients routinely receive less than optimal care as a result. Therefore, a clear initial priority should be greater collaboration among sleep health professionals trained in different disciplines, as well as increased research funding for comprehensive sleep medicine care. Particular areas warranting further study include the co-occurrence of insomnia disorder and SRBD, including whether co-occurring insomnia disorder and SRBD share a common pathophysiology that could be related to such negative health consequences as metabolic syndrome or depression. Indeed, occult SRBD may partially explain the predictive relation between insomnia disorder and cardiovascular disease, and undetected insomnia disorder may worsen quality of life in patients treated for OSA. Finally, patients suffering from both conditions will benefit greatly from enhanced continuity of care and the development and dissemination of effective treatment protocols for comorbid insomnia disorder and SRBD. Although several pilot studies have demonstrated that patients treated for both disorders experience additive health benefit, only one randomized trial has explored a formal treatment protocol. Factors such as disease severity and patient preferences will likely be especially important variables. In light of the emerging data, complex interaction of sleep disorders and symptoms, and increasing demand for comprehensive patient care including CBT-I and CBT for CPAP, it appears that the time for an interdisciplinary, integrative approach to sleep health care has arrived.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Wickwire has served as a scientific consultant for Health Media. Dr Collop has reported no potential conflicts of interest with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We thank the reviewers for their helpful observations.

AASM

American Academy of Sleep Medicine

AHI

apnea-hypopnea index

CBT

cognitive-behavioral therapy

CBT-I

cognitive-behavioral therapy for insomnia

CPAP

continuous positive airway pressure

FDA

Food and Drug Administration

HPA

hypothalamic-pituitary axis

OSA

obstructive sleep apnea

PSG

polysomnography

RDC

Research Diagnostic Criteria

SOL

sleep-onset latency

SRBD

sleep-related breathing disorder

TST

total sleep time

UARS

upper airway resistance syndrome

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Figures

Tables

Table Graphic Jump Location
Table 1 —Insomnia Complaints in Patients Evaluated for Sleep-Related Breathing Disorders

AHI = apnea-hypopnea index; EMA = early morning awakenings; MI = maintenance insomnia; NOA = number of nocturnal awakenings; OI = onset insomnia; OSA = obstructive sleep apnea; PSG = polysomnogram; RDI = respiratory disturbance index; SOL = sleep-onset latency; SRBD = sleep-related breathing disorder; WASO = wake after sleep onset.

Table Graphic Jump Location
Table 2 —Obstructive Sleep Apnea in Insomnia Disorder

TST = total sleep time; UARS = upper airway resistance syndrome. See Table 1 for expansion of other abbreviations.

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