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Sleep: Considerations in the Patient With Psychiatric Disorders

Sleep: Considerations in the Patient With Psychiatric Disorders. Rafael Pelayo, MD. Topics. Definition of insomnia Epidemiology of insomnia with psychiatric disorders Specific features of sleep and sleep disturbances in psychiatric disorders

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Sleep: Considerations in the Patient With Psychiatric Disorders

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  1. Sleep: Considerations in the Patient With Psychiatric Disorders Rafael Pelayo, MD

  2. Topics • Definition of insomnia • Epidemiology of insomnia with psychiatric disorders • Specific features of sleep and sleep disturbances in psychiatric disorders • Diagnostic evaluation of insomnia/sleep problems in psychiatric disorders • Causes/etiologies of sleep problems in specific psychiatric disorders • Behavioral treatment • Medication treatment

  3. Sleep in America:2005 National Sleep Foundation Poll 60 Weekdays Weekends 49% 50 31% 40 Respondents (%) 26% 24% 24% 30 16% 15% 10% 20 10 0 <6 6 to 6.9 7 to 7.9 8 Hours of Sleep/Night N=1,506 adults Mean=6.8 hours on weekdays; 7.4 hours on weekends National Sleep Foundation. 2005 Sleep in America Poll: Summary of findings. Available at: http://www.kintera.org/atf/cf/{F6BF2668-A1B4-4FE8-8D1A-A5D39340D9CB}/2005_summary_of_findings.pdf. Accessed January 23, 2008.

  4. Of the adults getting “a good night’s sleep,” only 26% get a few nights per month or less Sleep in America:Frequency of “A Good Night’s Sleep” 49% 24% 13% 26% 10% N=1,506 adults 3% National Sleep Foundation. 2005 Sleep in America Poll: Summary of findings. Available at: http://www.kintera.org/atf/cf/{F6BF2668-A1B4-4FE8-8D1A-A5D39340D9CB}/2005_summary_of_findings.pdf. Accessed January 23, 2008.

  5. Insomnia: Definition • Complaint of inadequate sleep despite sufficient opportunity • Typically complains of trouble falling asleep and/or staying asleep • Results in daytime impairment • Insomnia is a 24-hour condition

  6. National Institutes of Health State of the Science Conference Statement • Manifestations and Management Of Chronic Insomnia in Adults • Chronic insomnia is a major public health problem affecting millions of individuals, along with their families and communities • Little is known about the mechanisms, causes, clinical course, comorbidities, and consequences of chronic insomnia • Evidence supports the efficacy of cognitive-behavioral therapy and benzodiazepine receptor agonists in the treatment of this disorder • Very little evidence supports the efficacy of other treatments, despite their widespread use • Even treatments that have been systematically evaluated, the panel is concerned about the mismatch between the potential lifelong nature of this illness and the longest clinical trials, which have lasted 1 year or less • A substantial public and private research effort is warranted, including the development of research tools and the conduct of longitudinal studies and randomized clinical trials • There is a major need for educational programs directed at physicians, healthcare providers, and the public National Institutes of Health. Sleep. 2005;28:1049-1057.

  7. National Institutes of Health State of the Science Conference Statement (cont’d) • Manifestations and management of chronic insomnia in adults • Primary insomnia • Implies no other cause of sleep disturbance • Comorbid insomnia • Formerly known as secondary insomnia • Limited understanding of pathophysiology and direction of causality • Use of term “secondary” leads to undertreatment National Institutes of Health. Sleep. 2005;28:1049-1057.

  8. National Institutes of Health State of the Science Conference Statement (cont’d) • Manifestations and management of chronic insomnia in adults • Some evidence suggests high healthcare utilization • Direct and indirect costs of chronic insomnia estimated as tens of billions of dollars annually • Difficulty separating economic effects of insomnia from comorbid conditions National Institutes of Health. Sleep. 2005;28:1049-1057.

  9. Comorbid Insomnia • Medical conditions • Cardiopulmonary • Musculoskeletal • Psychiatric disorders • Depression • Anxiety Comorbid insomnia • Sleep disorders • Obstructive sleep apnea • Restless legs syndrome • Circadian rhythm • Pharmacological agents • Prescription/OTC medications • Nicotine • Substance abuse

  10. Impairments Associated With Insomnia • Impaired cognitive functioning • Negative quality-of-life measures • Increased incidence of bodily pain,poor general health • Increased future risk of psychiatric disorders • Decreased job performance, increased absenteeism • Increased risk of accidents • Increased healthcare costs

  11. Predisposing Factors Insomnia Threshold Preclinical Onset Short-term Chronic Model of Chronic Insomnia Precipitating Factors Perpetuating Factors • Biological traits • Psychological traits • Social factors • Medical illness • Psychiatric illness • Stressful life events • Excessive time in bed • Napping • Conditioning Adapted from: Spielman et al

  12. 40%-60% of outpatients and up to 90% of inpatients with a major depressive episode experience sleep problems

  13. Sleep in Depressed Patients • Patients experience: • Difficulty falling asleep • Frequent awakenings • Waking too early in the morning (terminal insomnia) • Fatigue when awake

  14. 9.0 7.8 8.0 7.0 6.0 5.0 5.0 Rate (%) 4.0 3.1 3.0 1.6 2.0 0.9 1.0 0.6 0.0 1 month 1-6 months 6-12 months 1-5 years 5-10 years 10 years Insomnia duration Place of Chronic Insomnia in the Course of Depressive and Anxiety Disorders Ohayon MM, Roth T. J Psychiatr Res. 2003;37:9-15.

  15. Sleep Timing • Sleep timing is influenced by homeostatic and circadian factors • The less we sleep, the more sleep we need and vice versa • Twice a day our alertness level peaks • Twice a day our sleepiness peaks

  16. Sleep Stages Electroencephalography Recordings Typical Nighttime Sleep Pattern in a Young Adult Awake Awake Stage 1 and REMa Stage 1 Stage 2 Stage 2 Stage 3 Stage 3 Stage 4 Delta 4 1 2 3 4 5 6 7 Time (hours) aRapid eye movement

  17. Key Polysomnographic Terms • Sleep latency • REM latency • Sleep efficiency • Wake after sleep onset (WASO) • Percent REM sleep • Percent slow-wave sleep (SWS) • Percent stage 1

  18. Polysomnographic Changes in Depression • Prolonged sleep latency • Increased WASO • Decreased SWS

  19. Polysomnographic Changes in Depression (cont’d) • Reduced REM latency • Prolonged first REM period • Density of the rapid eye movements during REM is more variable in depressed subjects, with periods when the eye movements are very sparse and periods when there are eye movement storms • Patients in remission from depression show a reduction in eye movement density, but reduced REM latency remains

  20. Comorbid Psychiatric Conditions: Major Depressive Disorder • Sleep-wake disturbances are experienced by 40% to 60% of outpatients with major depressive disorder (MDD)1 • 29% of patients with excessive sleepiness were diagnosed with MDD2 • 16% to 20% of patients with MDD and 36% of patients with atypical MDD report excessive sleepiness3,4 • Most common residual symptoms in outpatients with full response to fluoxetine were sleep-wake disturbances and fatigue5 1. Armitage R. Can J Psychiatry. 2000;45:803-809. 2. Roberts RE, Shema SJ, Kaplan GA, Strawbridge WJ. Am J Psychiatry. 2000;157:81-88. 3. Posternak MA, Zimmerman M. Arch Gen Psychiatry. 2002;59:70-76. 4. Horwath E, Johnson J, Weissman MM, Hornig C. J Affect Disord. 1992;26:117-125. 5. Nierenberg AA, Keefe BR, Leslie VC, et al. J Clin Psychiatry. 1999;60:221-225.

  21. Sleep Loss and Health: Physiologic Studies1-4 • In the laboratory setting, short-term sleep restriction leads to a variety of adverse physiologic sequelae, including: • Impaired glucose control • Increased cortisol • Increased blood pressure • Sympathetic activation • Increased appetite • Increased C-reactive protein • Immune function • These data suggest that sleep restriction may have health consequences (obesity, diabetes, cardiovascular disease) 1. Spiegel K, Tasali E, Penev P, Van Cauter E. Ann Intern Med. 2004;141:846-850. 2. Meier-Ewert HK, Ridker PM, Rifai N, et al. J Am Coll Cardiol. 2004;43:678-683. 3. Spiegel K, Leproult R, L'hermite-Balériaux M, Copinschi G, Penev PD, Van Cauter E. J Clin Endocrinol Metab. 2004;89:5762-5771. 4. Spiegel K, Sheridan JF, Van Cauter E.JAMA. 2002;288:1471-1472.

  22. 30 25 20 15 10 5 0 18-34 35-49 50-64 65-79 Insomnia By Age Group % Age Group Mellinger GD, Balter MB, Uhlenhuth EH. Arch Gen Psychiatry. 1985;42:225-232.

  23. Insomnia and Depression • Striking association between insomnia and depression • Insomnia early marker for onset of depression • May be linked by common pathophysiology1 • Need to treat both insomnia and depression 1. Benca RM. Mood disorders. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia, PA: Elsevier/Saunders; 2005:1311-1326.

  24. Physical Role, Health Role, Mental Function Physical Pain Perception Vitality Social Emotional Health Impact of Insomnia on Quality of Life Insomnia is associated with reduced mental health, vitality, and social functions Impact on SF-36 HRQOL Domainsa (N=3,445) 5 0 -5 -10 Deviation From Reference Group -15 -20 -25 Mild insomnia Severe insomnia -30 Congestive heart failure Clinical depression -35 aP≤0.001 except congestive heart failure association with pain, emotional role, and mental health Graph adapted from: Katz DA, McHorney CA. J Fam Pract. 2002;51:229-235. Taylor DJ, Lichstein KL, Durrence HH, Reidel BW, Bush AJ. Sleep. 2005;28:1457-1464.

  25. Dreaming and Mood Regulation • Why do we feel better after a good night of sleep? • What is it about sleep that restores us both physiologically and psychologically?

  26. Dreaming and Mood Regulation (cont’d) • Dreaming has been hypothesized to have an active self-regulatory role in emotional modulation, and that role can be disrupted due to various trait and state variables and their interactions

  27. Dreaming and Mood Regulation (cont’d) • Dreams that are spontaneously remembered are often accompanied by anxiety or other negative feelings • Dream content analysis of 250 healthy adults showed unpleasant effects predominating at a ratio of 2:1, with fear, anxiety, and anger as the most commonly identified1 • Patients suffering from an episode of major depression typically have reduced recall of dreams and absence of dream affect 1. Snyder, F. The phenomenology of dreaming. In: Madow L, Snow L, eds. The psychodynamic implications of the physiological studies on dreams. Springfield, IL: C.C. Thomas; 1970:124-151.

  28. Relation of Dreams to Waking Concerns • To test that dreams are influenced by the presleep waking emotional concerns of the sleeper and have an effect on waking adaptation, 20 depressed and 10 control subjects, who were all going through a divorce, were enrolled in a repeated measures study lasting 5 months • A Current Concerns test was administered on 3 occasions before nights when every REM period was interrupted to record recalled mental content • The degree of waking concern about the ex-spouse correlated significantly with the number of dreams in which the former partner appeared as a dream character • Those who were in remission at the follow-up evaluation had a higher percentage of well-developed dreams than those who remained depressed • Dreams of the former spouse reported by those in remission differed from those who remained depressed in the expression of dream affect and in the within-dream linkage among units of associated memory material • Dreams of the former spouse that are reported by those who are not in remission lack affect and connection to other memories Cartwright R, Agargun MY, Kirkby J, Friedman JK. Psychiatry Res. 2006;141:261-270.

  29. REM Sleep Reduction, Mood Regulation, and Remission in Untreated Depression • The contribution of ↑REM pressure through repeated, mild, reduction of REM sleep to remission from untreated depression was studied over a 5-month period in 20 depressed and 10 control volunteers • 60% of the depressed were in remission at the end of the study • 64% of the variance in remission could be accounted for by 4 variables: • The initial level of self-reported symptoms • The reported diurnal variability in mood • The degree of overnight reduction in depressed mood following interruptions of REM sleep • The quality of dream reports from these awakenings • Increased REM pressure is beneficial for those who are able to construct well-organized dreams • Increased REM pressure is beneficial for those who are able to construct well-organized dreams Cartwright R, Agargun MY, Kirkby J, Friedman JK. Psychiatry Res. 2006;141:261-270.

  30. Diagnosis and Treatment of Insomnia in Patients With Psychiatric Disorders Ruth M. Benca, MD, PhDUniversity of Wisconsin-Madison

  31. Evaluation of Insomnia Relies on a Subjective Report1,2 • Based primarily on subjective report of patient and/or family • Medical history, physical examination, and laboratory testing to assess comorbid conditions • Sleep diaries and questionnaires useful for diagnosis and to assess treatment response • Actigraphy • Polysomnography not usually indicated • National Institutes of Health State of the Science Conference Statement. Sleep. 2005;28:1049-1057. • Chesson A Jr, Hartse K, Anderson WM, et al. Sleep. 2000;23(2):237-241.

  32. Sleep Problems Are Often Multifactorial • Psychiatric illness-specific factors • Medications • Primary sleep disorders • Behavioral factors

  33. Psychiatric Illness-specific Factors • Mood disorders • Diurnal mood variation • Rapid cycling • Seasonal and circadian rhythm abnormalities • Anxiety disorders • Nocturnal panic attacks • Posttraumatic stress disorder and anxiety dreams • Schizophrenia • Exacerbation of psychosis at night

  34. Psychiatric Disorders Associated With Objective Changes in Sleep Architecture • Comparison of sleep EEGf in groups of patients with psychiatric disorders or insomnia to age-matched normal controls aTotal sleep time; bsleep efficiency; csleep latency ; dslow-wave sleep; erapid eye movement latency; felectroencephalographBenca RM, Obermeyer WH, Thisted RA, Gillin JC. Arch Gen Psych. 1992;49:651-668.

  35. Effects of Psycopharmacologic Agents on Sleep • Psychopharmacologic agents act on neurotransmitter systems involved in sleeping and waking • 5-hydroxytryptamine, acetylcholine, dopamine, histamine, norepinephrine • They can have clinically significant effects on sleep, which may enhance therapeutic effects (eg, treat insomnia) or result in side effects (eg, insomnia or daytime sleepiness) DeMartinis NA and Winokur A. CNS Neurol Disord Drug Targets. 2007;6:17-29.

  36. Effects of Psychopharmacologic Agents on Sleep (continued) • Antidepressants • Antipsychotics • Stimulants

  37. Antidepressants and Their Effect on Sleep • Most antidepressants disrupt sleep, although a minority of patients may report sedation • SSRIsa (fluoxetine, sertraline, paroxetine, citalopram) • Dual reuptake inhibitors (venlafaxine, duloxetine) • Bupropion • Monoamine oxidase inhibitors • Sedating antidepressants frequently used to treat insomnia associated with depressionb • Trazodone • Tricyclics (amitriptyline, doxepin) • Mirtazapine . aSelective serotonin reuptake inhibitors bUnapproved use by the US Food and Drug Administration (FDA) Peterson MJ, Benca RM. Psychiatr Clin North Am. 2006;29:1009-1032; Lippman S, Mazour I, Shahab. Southern Med J. 2001;94:866-873.

  38. Antidepressant and Their Effects on Sleep • The following drugs decrease sleep continuity • SSRIs – also suppress REMa sleep • Bupropion – has inconsistent effects on REM and SWSb • Venlafaxine – can also suppress REM sleep • MAOIsc – have a tendency to suppress REM and impair sleep continuity and decrease sleep time • The following drugs increase sleep continuity • Trazodone – can have sedating effects and suppress REM sleep • Mirtazapine – has prominent sedating effects • TCAsd – tend to result in sedation and REM suppression aRapid eye movement; bslow-wave sleep; cmonoamine oxidase inhibitors; dtricyclic antidepressants Mayers AG and Baldwin DS. Hum Psychopharmacol Clin Exp. 2005;20:533-559; Argyropoulos SV and Wilson SJ. Int Rev Psychiatry. 2005;17:237-245.

  39. Antipsychotics and Their Effect on Sleep • Typical agents include: • Thorazine • Haloperidol • Newer atypical agents include: • Clozapine: tends to enhance sleep continuity1,2 • Olanzapine: tends to enhance sleep continuity1,3 • Quetiapine: decreases sleep latency and wake time, increases sleep time and no changes in SWS, REM L, or REM density were noted4 • Risperidone: decreases awakenings, improves sleep quality, and increases SWS in patients with schizophrenia1,3 1 DeMartinis NA and Winokur A. CNS Neurol Disord Drug Targets. 2007;6:17-29; 2. Armitage R, Cole D, Suppes T, Ozcan ME. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:1065-1070; 3. Giménez S, Clos S, Romero S, Grasa E, Morte A, Barbanoj MJ. Psychopharmacology (Berl). 2007;190:507-516. Epub 2007 Jan 5; 4. Keshavan MS, Prasad KM, Montrose DM, Miewald JM, Kupfer DJ. J Clin Psychopharmacol. 2007;27:703-705.

  40. Stimulants and Their Effect on Sleep • Increasingly used for attention deficit disorder/ attention deficit hyperactivity disorder, depression, fatigue • Methylphenidate • Amphetamine • Modafinil • Effects include: • Decreased TST • Increased arousals • Suppressed REM sleep Mendelson WB, Caruso C. Pharmacology in sleep medicine. In: Poceta JS, Mitler MM, eds. Sleep Disorders: Diagnosis and Treatment. Totowa, NJ: Humana Press Inc.; 1998:137-160.

  41. Primary Sleep Disorders and Psychiatric Illnesses • Obstructive sleep apnea • Restless legs/periodic limb movements • Narcolepsy

  42. Obstructive Sleep Apnea • High rates of comorbidity with depression • For patients with either disorder, there is a 1 in 5 risk of having both disorders1 • Overlapping symptoms between apnea and depression, particularly: • Fatigue, decreased attention/concentration, lack of motivation, decreased enjoyment 1. Ohayon MM. J Clin Psychiatry. 2003;4:1195-1200.

  43. Psychiatric Medications May Exacerbate Sleep Apnea Through: • Weight gain • Atypical antipsychotics • Antidepressants • Mood stabilizers • Muscle relaxation • Benzodiazepines • Barbiturates • Decreased arousal threshold

  44. Sleep-related Movement Disorders • Many psychiatric medications can increase PLMSa that lead to arousals and sleep fragmentations • SSRIs, serotonin-norepinephrine reuptake inhibitors • Antipsychotics (typical and atypical) • Bupropion less likely to exacerbate restless leg syndrome/PLMS • Pharmacologic mechanisms thought to be associated with PLMS: • Reuptake inhibition of 5-hydroxytryptamine • Dopamine antagonism aPeriodic leg movements in sleep Yang C, White DP, Winkelman JW. Biol Psychiatry. 2005;58:510-514. Epub 2005 Jul 7; Nofzinger EA, Fasiczka A, Berman S, Thase ME. J Clin Psychiatry. 2000;61:858-862.

  45. Narcolepsy and Schizophrenia • The onset of both diseases occurs in the teenage years and 20s1 • It is unknown whether one disorder presents a greater risk for the other1 • Narcolepsy incidence is drastically lower than that of schizophrenia1 • Due to an overlap in symptoms, they are both commonly misdiagnosed1 • Hypnagogic/hypnopompic hallucinations associated with psychotic disorders2 • Patterns usually differ3 • Auditory hallucinations more common in schizophrenia • Visual or kinetic hallucinations more common in narcolepsy 1. Kishi Y, Konishi S, Koizumi S, Kudo Y, Kurosawa H, Kathol RG. Psychiatry Clin Neurosci. 2004;58:117-124; 2. Ohayon MM, Priest RG, Caulet M, Guilleminault C. Br J Psychiatry. 1996;169:459-467; 3. Dahmen N, Kasten M, Mittag K, Müller MJ. Eur J Health Econ. 2002;3(suppl 2):S94-S98.

  46. Narcolepsy and Schizophrenia (continued) • Psychotic form of narcolepsy vs stimulant-induced psychotic disorder?1,2 • Stimulants may lead to psychotic symptoms in narcoleptics • Misdiagnosis may lead to inappropriate treatment2 • Reports of treatment-refractive schizophrenia that turns out to be stimulant-responsive narcolepsy • Comorbid disorders can create treatment dilemmas2 • Stimulants often exacerbate psychotic symptoms • Antipsychotics may exacerbate sleepiness • Dahmen N, Kasten M, Mittag K, Müller MJ. Eur J Health Econ. 2002;3(suppl 2):S94-S98; • Benca RM. J Clin Psychiatry. 2007;68 (suppl 13):5-8.

  47. Behavioral Factors Contributing to Sleep Problems in Psychiatric Patients • Lack of daily structure • Irregular sleep patterns/napping • Psychosocial stressors

  48. Relationship Between Sleep and Psychiatric Disorders • Symptom overlap of insomnia and psychiatric disorders, particularly depression • Creates diagnostic issues • Psychological disorders are associated with sleep disturbance • Insomnia may be a risk factor in psychological disorders • Psychological medications may affect sleep 1. Wilson S, Argyropoulos S. Drugs. 2005;65:927-947.

  49. Treatment of Insomnia • Optimize treatment of psychiatric disorder • Promote good sleep hygiene • Consider cognitive behavior therapy • Consider medications to improve sleep Kupfer DJ, Reynolds CF. N Engl J Med. 1997;336:341-346.

  50. Practicing Good Sleep Hygiene • Increase exposure to bright light during the day1 • Time regular exercise for the morning and/or afternoon2,3 • Enhance sleep environment: dark, quiet, cool temperature2,3 • Avoid: • “Watching the clock” • Use of stimulants, eg, caffeine, nicotine, particularly near bedtime2,3 • Heavy meals or drinking alcohol within 3 hours of bed2 • Exposure to bright light during the night2,3 • Practice a relaxing routine around bedtime1-3 • Reduce time in bed; regular sleep/wake cycle1-3 1. Kupfer DJ, Reynolds CF. N Engl J Med. 1997;336:341-346; 2. NHLBI Working Group on Insomnia. 1998. NIH Publication. 98-4088; 3. Lippmann S, Mazour I, Shahab H.South Med J. 2001;94:866-873.

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