Supplements New Approaches to the Management and Treatment of Insomnia
The Impact and Prevalence of Chronic Insomnia and Other Sleep Disturbances Associated With Chronic Illness
Chronic insomnia may coexist with chronic physical and psychiatric conditions, and its prevalence is often higher among patients with these conditions than in the general population. Evidence suggests that insomnia as a feature of chronic disease tends to be more severe and persistent than insomnia that does not occur in the context of chronic illness. Furthermore, comorbid insomnia can have a profound negative impact on patients' quality of life and overall functioning, and may be associated with greater healthcare resource utilization. In some cases, treatment of the underlying disorder may improve sleep, whereas in other cases, treatment of the sleep symptoms may actually improve the underlying disorder. In addition, chronic insomnia may be a precursor to certain psychiatric comorbidities. Further research is needed not only to clarify the efficacy and safety of specific therapeutic approaches but also to further investigate the possibility that successful treatment of sleep disturbances may improve objective and subjective parameters of the disorders themselves. This article reviews the specific associations between chronic insomnia and a wide range of chronic physical and psychiatric disorders.
(Am J Manag Care. 2006;12:S221-S229)
Insomnia is extremely prevalent; community-based surveys in Western countries suggest that about one third of the population reports some form of difficulty falling asleep or staying asleep at any given time.1,2 For many of those affected, insomnia is a transient phenomenon, resolving within days or weeks; however, a substantial fraction of patients appears to suffer from chronic insomnia.
Chronic insomnia has been variously defined by frequency (usually =3 times per week) and duration (usually =1 month but sometimes longer), and typically involves some degree of daytime dysfunction. The persistence of insomnia as a complaint appears to be far greater in severe insomnia (ie, insomnia that is more frequent and of longer duration) than in mild insomnia; therefore, to a great extent, severe insomnia and chronic insomnia may describe similar phenomena.2,3 Prevalence estimates for chronic insomnia are clearly affected by differences in operational definitions. However, it seems reasonable to estimate that about 10% to 20% of the population in the United States and Western Europe experiences chronic insomnia.1,3
Chronic insomnia can coexist with a number of chronic physical and psychiatric conditions, including arthritis, cardiovascular (CV) disease, diabetes, and depression; and its prevalence is much higher among patients with such conditions than in the general population.2-4 Although insomnia is frequently treated as a minor or transient complaint, chronic insomnia has been shown to have a profoundly negative impact on patients' quality of life (QOL) and overall functioning, and is also associated with elevated consumption of healthcare resources.3,5-7 In addition, chronic insomnia may also be a precursor to, rather than a consequence of, certain psychiatric comorbidities, especially depression.8,9 This article reviews the specific associations between chronic insomnia and a wide range of chronic physical and psychiatric disorders.
Insomnia and Specific Disease States
Arthritis. The prevalence of chronic insomnia in patients with various forms of arthritis appears to be substantially greater than its prevalence in healthy controls. In a study of 429 patients with knee pain and osteoarthritis (OA), the proportions of patients reporting problems with sleep onset, sleep maintenance, and early-morning awakenings (all symptoms of insomnia) were 31%, 81%, and 51%, respectively. Predictors of greater numbers of these insomnia complaints included a greater number of involved joints; knee pain severity; CV disease; and poorer self-rated health, physical functioning, and physical performance.10 An analysis of sleep patterns in patients with OA showed that they spent significantly more time in lighter sleep (ie, significantly more time in stage 1 sleep and significantly less time in stage 2 sleep) than age-matched healthy controls.11
The importance of pain as a mediator of insomnia in OA is suggested by a longitudinal comparison of patients with OA before and after total hip arthroplasty (THA). Relative to sleep quality before THA, significant improvements in subjective and objective measures of sleep were observed after THA. Analysis of the results of actigraphy showed that after THA, patients experienced reductions in activity during sleep, as well as less insomnia, specifically more efficient and less fragmented sleep. The study authors concluded that a reduction in post-THA pain was the main factor contributing to improved sleep.12
The prevalence of insomnia complaints in patients with rheumatoid arthritis (RA) is greater than 50%.13 Although these complaints may involve problems with sleep onset, the most significant differences between patients with RA and healthy controls appear to be in sleep maintenance, sleep quality, and restorative sleep.13-15 Overall sleep architecture in patients with RA, with respect to the classic stages of sleep, resembles that of matched controls; however, these patients experience severely fragmented sleep with frequent awakenings and arousals.13,15,16
Although data on insomnia are reliable, there is conflicting evidence about the relationship between RA disease parameters and sleep architecture. Although no correlation was identified between inflammatory disease activity and sleep disruption in 1 study,15 a longitudinal study of sleep architecture and clinical symptoms demonstrated significant correlations between disrupted sleep architecture (including less restorative slow wave sleep), pain, and morning stiffness.17 Patients with RA also experience more periodic movements of the legs (PML), a symptom that has been associated with a number of disease states.13,15,16
Similar patterns of insomnia have also been observed in children with juvenile rheumatoid arthritis (JRA). Patients with JRA demonstrated 90% more arousals and awakenings than age-matched controls, as well as more shifts from deeper to lighter sleep and longer afternoon naps.18 Pain, but not disease activity, has been correlated with insomnia in patients with JRA, similar to the pattern observed in adults with RA.19
Insomnia is extremely prevalent (>75%) among patients with fibromyalgia and those with primary Sjögren's syndrome. In fibromyalgia, as in RA, insomnia has been associated with pain and morning stiffness. 20,21 It is important to emphasize that the consistent associations between poor sleep and pain in various arthritides may involve bidirectional causation: Pain can disrupt sleep, but poor sleep (especially loss of restorative sleep) can also lower the pain threshold and may contribute to increased daytime pain.20
Gastroesophageal Reflux Disorder (GERD). Patients with GERD frequently experience nighttime gastroesophageal reflux (GER) because of several factors: continued contact of stomach contents with the lower gastroesophageal sphincter, reduced esophageal motility, increased intra-abdominal pressure, and decreased gastric volume. These conditions are exacerbated by obesity, which is a risk factor for GERD and is common among patients with this disorder.22,23
The occurrence of GER events during sleep almost invariably leads to arousal, and sometimes to awakening. In a study of nighttime GER events using polysomnography, it was found that 45% (31/69) of such events occurred during periods of wakefulness after sleep onset. Of the 38 events that occurred during sleep, only 1 did not result in subject arousal.23 Although estimates of the prevalence of sleep complaints and/or insomnia among GERD patients are hard to find in the existing literature, the nearly invariant association of GER events with arousal suggests that these patients experience frequent insomnia and loss of restorative sleep.
Many patients with GERD also demonstrate obstructive sleep apnea (OSA).22-24 The frequent association between GERD and OSA has led researchers to postulate a direct causative link between respiratory events (apnea or hypopnea) and GER events.22 However, a polysomnographic study that recorded both respiratory and GER events failed to confirm such a link; GER events tended to occur independent of respiratory events.23 Both GERD and OSA share obesity as a common risk factor, and it is possible that the association of each condition with obesity provides a sufficient explanation for the association between the 2 conditions.22
Coronary Artery Disease (CAD). A number of studies have demonstrated an association between sleep disorders and the incidence of, and/or mortality caused by, CAD; the risk ratios for CAD associated with subjective insomnia complaints generally ranged from 1.5 to about 4.25 In some but not all of these studies, a gender association has also been identified, suggesting that men are at higher risk.26
In 1 of the few prospective studies of middle-aged adults, a general link between complaints of insomnia and CAD mortality was identified in a population-based study of 1870 subjects who had responded to a health survey. After a follow-up period of 12 years, difficulty in initiating sleep was associated with a 3-fold risk of CAD death in men; no such link was identified in women. The association in men remained significant after controlling for other CAD risk factors, including depression.26 However, in a number of other studies, adjustment for other CAD risk factors (especially depression) attenuated the relationship between insomnia and CAD, making it difficult to ascertain whether insomnia is an important causative factor in CAD or simply reflects the impact of risk factors common to both.25,27
The evidence base linking CAD to sleep disruption that is secondary to OSA or respiratory dysfunction is much firmer than that for more general sleep complaints. OSA has also been broadly linked to hypertension and other CV conditions.28 In 1 study, the prevalence of OSA (apnea index >10/hr) among 60 patients with angiographically confirmed CAD was 42% (25/60); 8 of the patients with OSA also demonstrated excessive daytime sleepiness.29
In a prospective study comparing CAD patients with and without OSA (defined as a respiratory disturbance index [RDI] of =10/hr), 37% of patients with CAD and OSA died during a 5-year follow-up period, compared with 9% of those with CAD and no OSA (P = .018); both groups were well matched at baseline with respect to other CAD risk factors. In a multiple conditional regression model, the association between elevated RDI and CAD mortality remained significant even after controlling for other risk factors.30
Studies of the relationship between OSA and CAD have not yet clarified the relative contribution of OSA per se, versus that of sleep disruption secondary to OSA, to the observed increased risk of CAD and CAD mortality. OSA causes a significant reduction in oxygen saturation, and the resulting CV stress may be sufficient to explain OSA-associated cardiac risk. Moreover, the associations between OSA and other CV conditions (such as hypertension), as well as the congruence between risk factors for CAD and for OSA (such as obesity), make it challenging to isolate and assess OSA-attributable risk.25 It is important to note that treatment of OSA with continuous positive airway pressure (CPAP) has been shown to reduce hypertension and nocturnal angina and to improve cardiac output in patients with congestive heart failure (CHF).31-34 These results tend to strengthen the causative link between OSA and CAD, even if the link is mediated through other CAD risk factors.25,28
CHF. Abnormal breathing patterns in patients with CHF were described independently in the early 19th century by Cheyne and Stokes, whose names were applied to a specific pattern known as Cheyne-Stokes respiration (CSR). CSR is characterized by a recurring pattern of central apneas and hypopneas, and is strongly associated with left ventricular insufficiency.35,36 The prevalence of CSR in patients with stable CHF ranges from 45% to 50%. Most CHF patients with CSR are men, but the significance of this finding is not yet known.35