Sleep Apnea Plus (OSAS+Insomnia) BY AHMAD YOUNES PROFESSOR OF THORACIC MEDICINE

1. Sleep Apnea Plus (OSAS+Insomnia) BYAHMAD YOUNESPROFESSOR OF THORACIC MEDICINE Mansoura Faculty of Medicine

2. Sleep Apnea Plus • Obstructive sleep apnea (OSA) and insomnia are two of the most commonly encountered sleep disorders. • The comorbidity of OSA and insomnia, also referred to as ‘Sleep apnea plus’ , was reported over 4 decades ago and various studies have examined the prevalence of insomnia in sleep apnea reporting prevalence rates ranging from 7.3% to 57.6% . • It is well recognized that both OSA and insomnia are -independently associated with cardiovascular disease; and psychiatric disorders. • The co-occurrence of OSA and insomnia has an additive effect on the comorbidities that have been independently associated with both of these conditions.

3. Sleep Apnea Plus • Activation of the hypo-thalamic pituitary-adrenal (HPA) axis is believed to be one of the major mechanisms underlying the pathogenesis of both the cardiovascular and psychiatric disorders that are encountered in OSA and insomnia. • OSA is characterized by intermittent hypoxia, which can lead to oxidative stress, systemic inflammation, vascular endothelial dysfunction, and an increase in sympathetic nervous system (SNS) activity, putting OSA patients at risk for cardiovascular disorders . • The allostatic challenge induced by the arousals of OSA is also thought to activate the HPA axis . • This elevated SNS and HPA axis activity can lead to an up regulation of the renin-angiotensin-aldosterone system, potentially leading to the development of hypertension ,an increase in cortisol levels, which have been implicated in psychiatric disorders such as depression.

14. Sleep Apnea Plus • Corticotropin releasing factor hyperactivity, due to early-life stress or genetic predisposition, can lead to an amplification of the stress response, followed by prolonged and exaggerated sleep difficulties following stress and the subsequent development of chronic insomnia . • This chronic hyperarousal puts insomnia patients at risk for cardiovascular disease and mood disorders also associated with HPA axis hyperactivity. • Insomnia may be a consequence of the enhanced HPA axis activity seen in OSA . Alternatively, insomnia may cause or exacerbate OSA by creating repeated sleep fragmentation, which can cause disruptions of the upper airway muscle tone, leading to greater airway collapsibility and the development of OSA.

15. Sleep Apnea Plus • The shared physiological mechanism of HPA hyperactivity underlying both OSA and insomnia may explain the high comorbidity of these two sleep disorders. • United States National Health and Nutrition Examination Survey (NHANES) reports a 43% frequency of insomnia in OSA(n =546) versus 30% frequency of insomnia in individuals without OSA (n= 12,047).

16. Sleep Apnea Plus • Results from the Icelandic Sleep Apnea Cohort Study indicate a 57.6% frequency of insomnia in polysomnographically diagnosed obstructive sleep apnea (n= 824) versus 31% among controls from the general population (n= 762) in Iceland. • Finally, data from the prospective Norwegian Hordaland Health Study (n =6892) found a much lower frequency of comorbid insomnia in sleep apnea of 7.3% versus a 4.9% frequency of insomnia without sleep apnea .

17. Insomnia - What is it? • A broad term denoting unsatisfactory sleep. • Trouble falling asleep, staying asleep, or waking too early. • Perception that sleep is inadequate or abnormal • Common problem • A symptom, not a disease or sign, therefore difficult to measure

18. 3 P’s of Short term Insomnia • Predisposition • Anxiety, depression, etc. • Precipitation • Sudden change in life • Perpetuation • Poor sleep hygiene • Precipitating causes lower the threshold for short term insomniain people with predisposing and perpetuating causes as well as further lowers the threshold for chronic insomnia • Start aggressive treatment in the short term insomnia phase, before the patient goes into CHRONIC insomnia

19. Diagnostic criteria for insomniaAASM 2014 • Complaints not explained by inadequate opportunity or circumstances • Sleep disturbance and associated daytime symptoms occur at least 3 times/week • Sleep/wake difficulty not better explained by another sleep disorder • Short-term • Present for ≤ 3 months • Chronic • Present for ≥ 3 months • One or more of : • Difficulty initiating sleep • Difficulty maintaining sleep • Waking up earlier than desired • One or more of : • Fatigue/malaise • Attention, concentration, or memory impairment • Impaired social, family, occupational, or academic performance • Mood disturbance/irritability • Daytime sleepiness • Reduced motivation/energy/ initiative • Proneness for errors/accidents • Concerns about or dissatisfaction with sleep

20. Diagnostic Criteria for Insomnia • The International Classification of Sleep Disorders, second edition (ICSD-3) lists diagnostic criteria for insomnia that include requirements for an insomnia sleep complaint , adequate opportunity and circumstances for sleep, and some form of daytime impairment related to the sleep difficulty. • The sleep complaints associated with insomnia include difficulty initiating sleep (sleep-onset insomnia), difficulty maintaining sleep (sleep-maintenance insomnia), or (waking up too early). • A diagnosis of insomnia requires that patients must report at least one of these insomnia complaints. However, it is not uncommon for individual patients to report all of them.

21. PREVALENCE OF INSOMNIA AND RISK FACTORS It has been estimated that insomnia complaints occur on at least a few nights per year in 33% to 50% of the adult population. Insomnia complaints plus symptoms of impairment due to insomnia occur in 10% to 15% of the population. Specific insomnia disorders occur in 5% to 10%. A number of risk factors for the development of insomnia have been identified, including older age, female gender, co-morbid problems (depression and other psychiatric disorders, substance abuse), shift work, unemployment, and lower socio-economic status.

22. PREVALENCE OF INSOMNIA AND RISK FACTORS • Some studies suggest that single, divorced, and separated patients have greater insomnia rates than married patients. • Up to one third of all cases of insomniaare associated with a mental disorder. • The most common cause of insomnia in patients evaluated by a physician is insomnia due to or associated with depression. • Insomnia occurs in the majority of patients (80%) with major depressive or chronic pain disorders.

24. INSOMNIA SUBTYPES The three most common insomnia disorders include adjustment insomnia, psychophysiologic insomnia, and insomnia due to a mental disorder. A number of other sleep disorders not included in this group can also present with complaints of insomnia. The sleep apnea syndromes can be associated with repetitive arousal and sleep-maintenance problems. In patients with sleep apnea, insomnia symptoms are more likely to be present in women than in men. The circadian rhythm sleep disorders (CRSDs) can also be associated with insomnia complaints including the delayed sleep phase syndrome (sleep-onset insomnia) and the advanced sleep phase syndrome (early morning awakening).

25. INSOMNIA SUBTYPES • In CRSD free-running type, patients may report periods of insomnia alternating with hypersomnia. • The restless legs syndrome/periodic limb movement disorder can also be associated with symptoms of insomnia. • Other classifications of insomnia divide disorders into primary and secondary (co-morbid) insomnia. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), lists diagnostic criteria for primary insomnia . This type of insomnia would include adjustment insomnia, psychophysiologic insomnia, paradoxical insomnia, idiopathic insomnia, and inadequate sleep hygiene. • Insomnia associated with a mental disorder is termed secondary or co-morbid insomnia.

26. Diagnostic Criteria for Primary Insomnia A. The predominant complaint is difficulty initiating or maintaining sleep for at least 1 month. B. The sleep disorder causes clinically significant distress or impairment of social, occupation, or other important areas of functioning. C. The sleep disturbance does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or a parasomnia. D. The disturbance does not occur exclusively during the course of another mental disorder (e.g., Major Depressive Disorder, Generalized Anxiety Disorder, a delirium). E. The disturbance is not due to the direct physiologic effects of a substance (e.g., a drug of abuse, a medication) or a general medication condition.

27. PHYSIOLOGIC FINDINGS IN PRIMARY INSOMNIA • Increased high frequency EEG activity, increased whole body and brain metabolic activity, elevated heart rate, and sympathetic nervous system activation(decreased heart rate variability) during both day and night in patients with insomnia. • These findings suggest that patients with insomnia are in a state of hyper-arousal. • Functional neuro-imaging has found greater global cerebral glucose metabolism during sleep and while awake and a smaller decline in relative metabolism from waking to sleep in wake-promoting regionsin patients with insomnia compared with normal controls .Reduced metabolism was found in the pre-frontal cortex of patients with primary insomnia while awake.

28. PHYSIOLOGIC FINDINGS IN PRIMARY INSOMNIA • It is not clear whether these findings represent cause or effect. • A recent study of magnetic resonance spectroscopy found a global reduction in gamma-aminobutyric acid (GABA) in non medicated patients with primary insomnia compared with normal controls. This neurotransmitter is generally inhibitory and higher levels would be expected to promote sleep.

29. Adjustment Insomnia • Adjustment insomnia, at least in milder forms, is experienced by a large percentage of otherwise normal sleepers at some time in their lives. • The 1-year prevalence of adjustment insomnia in adults is 15% to 20%. • The problem resolves with time in most cases. If the insomnia persists beyond 3 months, it is considered a chronic insomnia. • Some cases of psycho-physiologic insomnia may have started as adjustment insomnia. • Most patients with adjustment insomnia are not evaluated by a sleep specialist. However, they may request hypnotic medication from their primary care physician or self-medicate with over-the-counter sleep aids.

30. Adjustment Insomnia Key Features Adjustment insomnia is a disorder of less than 3 months ’ duration that is in response to a definitely identifiable event . It is expected to resolve but may require treatment if a significant impact on sleep and daytime functioning is noted. Patients with adjustment insomnia can develop a chronic insomnia disorder. Differential Diagnosis Psycho-physiologic and paradoxical insomnia typically last longer than 3 months. Some patients with psycho-physiologic insomnia report the onset of their problem after an acute stress. Insomnia due to medical disorder or medication is temporally associated with starting a medication or the onset of the medical disorder. Insomnia due to mental disorder typically lasts longer than 3 months and waxes and wanes with the mental disorder. Also may develop if the patient with adjustment insomnia develops depression as a result of the acute stressor.

32. Treatment • Benzodiazepine receptor agonists (BZRAs), ramelteon, anxiolytics, or counseling are used to treat adjustment insomnia (if necessary).

33. Psycho-physiologic Insomnia Psycho-physiologic insomnia is the most common primary insomnia type seen in sleep clinics and it is often called “conditioned or learned insomnia.” Key Features Conditioned sleep difficulty, heightened arousal in bed, and learned sleep-preventing associations are the essential characteristics of this disorder. Mental arousal (“racing mind/ thoughts”) occurring when trying to go to sleep is a common complaint. The patient becomes conditioned so that the bedroom is a “cue” to develop tension, anxiety, and inability to fall asleep. Some patients sleep better away from home. Patients typically can fall asleep during monotonous activities but not after getting into bed and trying to sleep. For example, a patient may fall asleep while watching television in the living room but become wide awake after entering the bedroom and attempting to sleep.

34. Psycho-physiologic Insomnia This disorder may start after a precipitating event (death in family, job stress) but then persists owing to perpetuating behaviors even after the precipitating event has resolved. Patients may report a lifelong pattern of being “light sleepers” or episodically poor sleep . Psycho-physiologic insomnia is present in 1% to 2% of the general population and 12% to 15% of patients seen in sleep centers. This disorder is more common in women than in men. If left untreated, the disorder may persist for decades with periodic worsening.

35. Diagnostic Criteria of Psycho-physiologic Insomnia Patient’s symptoms meet the criteria for insomnia. Evidence of conditioned sleep difficulty and/or heightened arousal in bed as indicated by one or more of the following: i. Excessive focus on sleep, anxiety about sleep. ii. Difficulty falling asleep in bed at desired bedtime or during planned naps BUT no difficulty falling asleep during other monotonous activities when not intending to sleep. iii. Ability to sleep better away from home. iv. Mental arousal in bed characterized by either intrusive thoughts or a perceived inability to volitionally cease sleep-preventing mental activity. v. Heightened somatic tension in bed reflected by a perceived inability to relax the body sufficiently to allow the onset of sleep. C. The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, mental disorder, medication use, or substance abuse.

36. Psychophysiologic Insomnia Polysomnography Although sleep studies are not indicated for evaluation of most patients with insomnia, typical findings include a prolonged sleep latency (>30 min), increased WASO, and decreased sleep efficiency. Sometimes, the reverse first-night effect is noted with better sleep in the sleep center than at home. Patients may underestimate their sleep duration but not the “gross underestimation” seen in paradoxical insomnia. Sleep Logstypically show a long sleep latency, reduced TST, increased WASO, and a large number of nocturnal awakenings. Typically, there is considerable night-to-night variability in sleep quality.

37. Psychophysiologic Insomnia • There may also be evidence of poor sleep hygiene with prolonged time in bed, napping, and variability in wake times. • Actigraphy Findings may overestimate or underestimate TST when compared with PSG. Actigraphy typically provides a better estimate of TST than of wake time. Typical actigraphic findings would substantiate patient reports and findings from sleep logs. • Treatment CBT for insomnia and pharmaco-therapy are treatment options.

38. Paradoxical Insomnia (Sleep State Misperception) Key Features The severe degree of sleep disturbance reported in patients with paradoxical insomnia is out of proportion to the relatively mild daytime impairment and the severity of sleep disturbance documented on PSG. • Patients often report little or no sleep on many nights followed by days with relatively minimal dysfunction and no napping. • Patients with paradoxical insomnia often report hearing every noise in the house while in the bedroom and/or actively thinking for the entire night.

39. Paradoxical Insomnia (Sleep State Misperception) • Daytime impairment reported is consistent with other types of insomnia but is much less severe than expected, given the severe level of sleep deprivation reported. • There are no intrusive sleep episodes or serious mishaps due to loss of alertness, even following nights reportedly without sleep . • Paradoxical insomnia is found in less than 5% of insomnia patients evaluated in sleep clinics. • Sleep Log Data information is usually consistent with the patient’s complaints, but NOT consistent with objective evidence (from PSG or actigraphic data). There may be nights with little or no sleep reported followed by days with no napping.

40. Diagnostic Criteria of Paradoxical Insomnia (Sleep State Misperception) A. Symptoms meet criteria for insomnia. B. One or more of the following criteria apply: i. Chronic pattern of little or no sleep most nights with rare nights during which relatively normal amount of sleep is obtained. ii. Sleep log data during 1 or more weeks of monitoring show an average sleep time well below published age-adjusted normative values, often with no sleep at all indicated for several nights per week: typically there is an absence of naps following such nights. iii. The patient shows a consistent mismatch between objective findings from PSG or actigraphy and subjective sleep estimates derived from either sleep report or sleep diary.

41. Diagnostic Criteria of Paradoxical Insomnia (Sleep State Misperception) C. At least one of the following is observed: i. Constant or near-constant awareness of environmental stimuli throughout most nights. ii. The patient reports a pattern of conscious thoughts or rumination throughout most nights while maintaining a recumbent posture. D. Daytime impairment reported is consistent with other types of insomnia subtypes but is much less severe than expected, given the extreme level of sleep deprivation reported; there is no report of intrusive daytime sleep episodes, disorientation, or serious mishaps due to marked loss of alertness or vigilance, even following reportedly sleepless nights. F. The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, mental disorder, medication use, or substance abuse.

42. Paradoxical Insomnia (Sleep State Misperception) • PSG Findingsindicated lack of significant deficits in TST or an excessively prolonged sleep latency. If abnormalities are noted on the PSG, they are less severe than reported by the patient. Reported sleep latency and WASO at least 1.5 times the PSG values. • Multiple Sleep Latency Test The sleep latency in patients with paradoxical insomnia is typically normal or slightly decreased.

43. Paradoxical Insomnia (Sleep State Misperception) • Differential Diagnosis Unlike idiopathic insomnia, paradoxical insomnia does not begin in childhood. In contrast to psycho-physiologic insomnia, patients with paradoxical insomnia are more prone to report little or NO sleep on many nights. However, some patients with psycho-physiologic insomnia also underestimate their nocturnal sleep. Whereas patients with paradoxical insomnia often report being aware of the environment for the entire night or ruminating on problems, they tend to have less prominent sleep-preventing associations compared with patients with psycho-physiologic insomnia. • Treatment CBT of insomnia (CBTI), pharmaco-therapy, or both are recommended.

44. Idiopathic Insomnia • Idiopathic insomnia is also called childhood-onset insomnia.The patient usually recalls the insidious onset of the insomnia problems in childhood. • The history is one of lifelong insomnia problems . • Key Features Patients with idiopathic insomnia report this problem since childhood with no periods of significant remission.There is no identifiable cause or precipitating factor. The onset is often insidious. • Idiopathic insomnia occurs in less than 10% of patients with insomnia.

46. Idiopathic Insomnia Polysomnography findings include a long sleep latency, increased WASO, reduced TST, and low sleep efficiency. These findings are not specific for idiopathic insomnia. Sleep LogFindings are typically consistent with the patient’s complaints. Differential DiagnosisWhereas idiopathic insomnia has an insidious onset in childhood, psycho-physiologic insomnia starts in adulthood and the time of onset can often be defined. In paradoxical insomnia, a more severe abnormality of sleep is usually reported and the disorder does not start at an early age. Treatment CBTI, pharmaco-therapy, or both are options.

47. Inadequate Sleep Hygiene Key Features • This disorder is characterized by behaviors that can potentially disrupt sleepsuch as exercise or ingestion of caffeine or alcohol near bedtime . • Patients often have irregular bedtimes and wake times and spend too much time in bed. • Napping is another behavior that makes nocturnal sleep more difficult.

48. Diagnostic Criteria of Inadequate Sleep Hygiene A. Symptoms meet criteria for insomnia. B. The insomnia is present for at least 3 months. C. Inadequate sleep hygiene practices are evident as indicated by the presence of at least one of the following: • Improper sleep scheduling consisting of frequent daytime napping, selecting highly variable bedtimes or rising times . • Routine use of products containing alcohol, nicotine, or caffeine, especially in periods preceding bedtime. iii. Engagement in mentally stimulating, physically activating, or emotionally upsetting activities too close to bedtime. iv. Frequent use of the bed for activities other than sleep (TV watching, reading, studying, snacking, thinking, planning). v. Failure to maintain a comfortable sleeping environment. D. The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, mental disorder, medication use, or substance abuse.

50. The importance of poor sleep hygiene in the development of insomnia is unknown. • Although sleep hygiene education is a part of most treatment programs for insomnia, there is no evidence for effectiveness of this intervention when used alone. • Insomnia due to inadequate sleep hygiene may develop in adolescence or adulthood. • Insomnia due to inadequate sleep hygiene occurs in approximately 5% to 10% of insomnias evaluated in a sleep center. • The condition is present in 1% to 2% of adolescents and young adults.