Outcomes and Multidisciplinary Treatment of Insomnia. David N. Neubauer, M.D. Johns Hopkins University School of Medicine

Transcription

1 Outcomes and Multidisciplinary Treatment of Insomnia David N. Neubauer, M.D. Johns Hopkins University School of Medicine

2 Insomnia as a Disorder INSOMNIA More than 1 type of disturbance may be present Symptoms may vary over time Difficulty Falling Asleep Difficulty Staying Asleep (eg, inability to return to sleep after awakening) Waking Too Early Poor Quality of Sleep Next-Day Consequences Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association Press; 1994.

3 Insomnia Epidemiology Prevalence approximately 30% of general population 10% of population has associated symptoms of daytime functional impairment up to 50% prevalence in clinical practices NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults. (June 15, 2005)

4 Insomnia Consequences Nighttime experience Daytime complaints Quality of life Absenteeism and decreased productivity Increased healthcare costs Societal burden Future health risks Increased fall risk

5 Insomnia Daytime Complaints Fatigue, exhaustion, tiredness Poor concentration and memory Irritability, moodiness Relationship problems Decreased enjoyment

6 Insomnia and Quality of Life Physical Functioning 100 Mental Health Physical Role Emotional Role Bodily Pain Social Functioning 100 Vitality General Health Good Sleepers (n=391) Mild Insomnia (n=422) Severe Insomnia (n=240) Axes represent subscales of the SF-36. All P values <.05 (range ). SF-36: Short Form Health Survey of the Medical Outcomes Study (36 item). Léger D, et al. Psychosom Med. 2001; 63:49-55.

7 Insomnia Etiology Causes and comorbidities Situational disturbances Psychological conditioning hyperarousal Poor sleep habits Psychiatric disorders Medical disorders Sleep disorders Medication effects Often multifactorial Neubauer DN. Insomnia. Prim Care. 2005;32:

8 Insomnia: Two General Types Primary Insomnia independent from other disorders Comorbid Most common category Presumably associated with co-occurring medical, psychiatric, or sleep disorders Promotes independent treatment of insomnia and associated disorders Replaces secondary insomnia attribution NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults. (June 15, 2005)

9 Models of Primary Insomnia Psychophysiological Hyperarousal EEG activation Cortisol and cytokine abnormalities Thermoregulation Neuroimaging Neubauer, David N. and Kelleen N. Flaherty Pathophysiology, Associations, and Consequences of Insomnia Handbook of Sleep Disorders. Edited by Kushida, C. Taylor and Francis Group, LLC New York, NY. 2010

10 Common Insomnia Comorbidities Medical Cardiac, pulmonary, rheumatologic, neurologic, endocrine, genitourinary, pain syndromes Psychiatric Mood disorders, anxiety disorders, substance abuse Sleep Circadian rhythm disorders, RLS Sleep disordered breathing Obstructive Central

11 More health problems Worse sleep Percent of community dwelling subjects (ages years) with any symptom of insomnia by number of medical conditions Reported Number of Medical Conditions N = 1506 Foley D, Ancoli Israel S, Britz P, Walsh J. Sleep disturbances and chronic disease in older adults: Results of the 2003 National Sleep Foundation Sleep in America survey. J Psychosom Res. 2004;56:

12 Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems. Sleep. 2007;30:

13 Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems. Sleep. 2007;30:

14 Medical Insomnia Increases Future Health Risks Hypertension (Japan) Coronary artery disease mortality (Sweden) Diabetes mellitus type II (Sweden, Germany) Psychiatric Mood disorders Anxiety disorders Substance abuse Suicide

15 Insomnia: Evaluation and Treatment

16 Evaluating Insomnia Screen patients for sleep-related symptoms Routine history Review of systems Recognize patients with increased risk for insomnia and other sleep disorders Do you feel that you are sleeping well at nighttime and are fully alert throughout the daytime?

17 Sleep Logs and Diaries Helpful in revealing patterns of sleep disturbance Sleep onset Sleep maintenance Advanced or delayed sleep phase tendencies Insufficient time in bed Helpful to monitor effects of treatment strategies Daily chart vs. graph approaches

18 Insomnia Treatment Approaches Education Sleep hygiene measures Behavioral and cognitive therapy techniques Pharmacotherapy Phototherapy and circadian manipulations Sleep medicine specialist consultation and sleep laboratory testing

19 Who Treats Insomnia Physicians Primary care Psychiatrist Multiple specialties Sleep medicine MDs Behavior sleep medicine specialists Nurses Nurse practitioners Physician assistants Therapists Collaborative efforts of all providers

20 Principles of Sleep Hygiene Regular sleep/wake cycle Regular exercise morning/afternoon Increase exposure to bright light during day Avoid exposure to bright light during night Avoid heavy meals/drinking <3 hrs of bedtime Enhance sleep environment Avoid caffeine, alcohol, nicotine Relaxing routine NHLBI Working Group on Insomnia NIH Publication

21 Strategy Cognitive therapy Relaxation training Sleep restriction Stimulus control Behavioral Strategies for Treating Insomnia Goal Bootzin RR, Perlis ML. J Clin Psych. 1992;53(suppl): Challenge patient s dysfunctional beliefs and misconceptions about sleep and insomnia Reduce physiologic and cognitive arousal at bedtime. Techniques include progression muscular relaxation, transcendental meditation, yoga, biofeedback Improve sleep continuity by limiting time spent in bed Relate to the bed/bedroom solely as a place for sleep or sexual activity

22 Cognitive-Behavioral Therapy (CBT) Multicomponent approach Sleep education and sleep hygiene advice Stimulus control and sleep restriction Cognitive psychotherapy Individual or group format Manualized or unstructured Numerous studies and meta-analyses demonstrate efficacy and long-term benefits

23 Advantages Cognitive-Behavioral Therapy (CBT) Efficacy and durability May address key psychological issues Appealing for some Disadvantages Availability of qualified therapists Cost in time and money Lack of immediate results Unappealing for others

24 CBT Outcomes CBT vs RT vs Placebo in 75 Chronic Primary Insomnia Patients Objective Measures of Efficacy Following 6 Weeks of Treatment 380 P= P=0.02 Total Sleep Time (Min) * Middle Wake Time After Sleep Onset (Min) * Placebo CBT RT Placebo CBT RT *RT vs placebo was nonsignificant. Edinger JD, et al. JAMA. 2001;285(14):

25 CBT Outcomes 105 Pretreatment 59 Studies Posttreatment (avg=5 wks) P< N = Minutes Minutes Sleep Onset Latency Wake After Sleep Onset CBT = cognitive-behavioral therapy Morin CM, et al. Am J Psychiatry. 1994;151: Total Sleep Time 0

26 Recent Insomnia Behavioral Treatment Reports Self-help therapy Internet-based interventions CBT with and without pharmacotherapy CBT for specific comorbid insomnia populations (depression, cancer) CBT and mindfulness medication Brief behavioral treatment Primary care nurses trained as sleep therapists Intensive sleep retraining

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28 Substances Used for Sleep: Past to Present Fermented beverages Plant preparations Laudanum (opium/alcohol) Chloral hydrate Barbiturate and related compounds Antihistamines Benzodiazepine hypnotics Nonbenzodiazepine hypnotics Selective melatonin receptor agonist

29 Insomnia: Recent Highlights Pharmacologic Developments Pharmacodynamic innovations New mechanism of action medications Pharmacokinetic innovations Extended release hypnotics FDA insomnia treatment indications Duration of use Differentiating sleep onset and maintenance DEA scheduling for hypnotics

30 Insomnia Treatment Medications (FDA-Approved) Benzodiazepine receptor agonist hypnotics Benzodiazepine structure Nonbenzodiazepine Selective melatonin receptor agonist

31 Benzodiazepine Mechanisms Gamma aminobutyric acid (GABA) Predominant inhibitory neurotransmitter in CNS A primary inhibitory neurotransmitter in the ventrolateral preoptic nucleus (VLPO) Benzodiazepine receptor agonists (BZRA) bind to BZ receptor site on GABA A receptor complex Enhance GABA activation of chloride ion channel Hyperpolarizes GABAergic neurons Landolt HP, Gillin JC. CNS Drugs. 2000;15: Mendelson WB, et al. Sleep Med Rev. 2004;8:7-17.

32 GABA A Receptor Complex Extracellular Cl - Cl - Cl - γ Cl - Cl - BZ receptor site Cell membrane Intracellular Cl- Cl - Cl - Möhler H et al. (2002), J Pharmacol Exp Ther 300(1):2-8; Rowlett JK et al. (2005), CNS Spectr 10(1):40-48

33 Benzodiazepine Receptor Agonist Hypnotics Positive allosteric modulators of GABA responses at GABA A receptors Benzodiazepine and nonbenzodiazepine All promote rapid sleep onset Duration of action promoting sleep maintenance or causing residual sedation depends upon the dose and elimination halflife

34 Selective Melatonin Receptor Agonist Ramelteon (Rozerem) Selective melatonin receptor agonist MT 1 : attenuation of circadian alerting signal MT 2 : circadian phase reinforcement or shifting Acts on the suprachiasmatic nucleus Influences the circadian rhythm effects on the sleep-wake cycle No abuse liability, not a DEA controlled substance

35 Circadian and Homeostatic Regulation of Sleep Edgar DM, Dement WC, Fuller CA, et al. Effect of SCN lesions on sleep in squirrel monkeys: evidence for opponent process in sleep-wake regulation. J Neurosci. 1993;13:

36 FDA Approved Insomnia Medications as of February, 2010 Generic name Brand name Available doses (mg) Elimination half life (hr) Benzodiazepine receptor agonists Benzodiazepines Immediate release Estazolam ProSom 1, Flurazepam Dalmane 15, Quazepam Doral 7.5, Temazepam Restoril 7.5, 15, 22.5, Triazolam Halcion 0.125, Nonbenzodiazepines Immediate release Eszopiclone Lunesta 1, 2, Zaleplon Sonata 5, 10 1 Zolpidem Ambien 5, Nonbenzodiazepines Extended release Zolpidem ER Ambien CR 6.25, Nonbenzodiazepines Alternate delivery Zolpidem oral spray Zolpimist 5, 10 ~2.5 Zolpidem sublingual Edluar 5, 10 ~2.5 Selective melatonin receptor agonist Ramelteon Rozerem

37 New Directions in Insomnia Pharmacotherapy Candidates in development Alternate delivery BZRA formulations* Doxepin ultra-low dose 5-HT 2A antagonists Orexin (Hypocretin) receptor antagonists CRF antagonists Neurosteroids, Substance P antagonists H 1 receptor antagonists (selective) H 3 receptor agonists

38 New Directions in Insomnia Pharmacotherapy MEDA Pharmaceuticals: Edluar NovaDel: Zolpimist

39 Summary Insomnia is a common clinical problem that is chronic for many individuals Effective treatment approaches include behavioral, cognitive, and pharmacologic interventions Insomnia treatment may involve the collaboration of a variety of health care providers There have been significant developments in both pharmacodynamic and pharmacokinetic approaches New approaches to delivering both cognitivebehavioral and pharmacologic insomnia therapies are being investigated.

40 Outcomes and Multidisciplinary Treatment of Insomnia David N. Neubauer, MD Johns Hopkins University School of Medicine References: 1. American Psychiatric Association, American Psychiatric Association. Task Force on DSM-IV. Diagnostic and Statistical Manual of Mental Disorders : DSM-IV. 4th ed. Washington, DC: American Psychiatric Association; Bootzin RR, Perlis ML. Nonpharmacologic treatments of insomnia. J Clin Psychiatry. 1992;53 Suppl: Buysse DJ. Chronic insomnia. Am J Psychiatry. 2008;165(6): Carey TJ, Moul DE, Pilkonis P, Germain A, Buysse DJ. Focusing on the experience of insomnia. Behav Sleep Med. 2005;3(2): Ebben MR, Spielman AJ. Non-pharmacological treatments for insomnia. J Behav Med. 2009;32(3): Edinger JD, Means MK. Cognitive-behavioral therapy for primary insomnia. Clin Psychol Rev. 2005;25(5): Edinger JD, Olsen MK, Stechuchak KM, et al. Cognitive behavioral therapy for patients with primary insomnia or insomnia associated predominantly with mixed psychiatric disorders: A randomized clinical trial. Sleep. 2009;32(4): Edinger JD, Wohlgemuth WK, Radtke RA, Marsh GR, Quillian RE. Cognitive behavioral therapy for treatment of chronic primary insomnia: A randomized controlled trial. JAMA. 2001;285(14): Espie CA, Broomfield NM, MacMahon KM, Macphee LM, Taylor LM. The attentionintention-effort pathway in the development of psychophysiologic insomnia: A theoretical review. Sleep Med Rev. 2006;10(4): Espie CA, Fleming L, Cassidy J, et al. Randomized controlled clinical effectiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer. J Clin Oncol. 2008;26(28): Espie CA, Inglis SJ, Tessier S, Harvey L. The clinical effectiveness of cognitive behaviour therapy for chronic insomnia: Implementation and evaluation of a sleep clinic in general medical practice. Behav Res Ther. 2001;39(1):45-60.

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