Sleep Disorders: Assessment and Therapeutic Options

Transcription

1 Sleep Disorders: Assessment and Therapeutic Options John W. Winkelman MD, PhD Chief, Sleep Disorders Clinical Research Program Departments of Psychiatry and Neurology Massachusetts General Hospital Professor of Psychiatry Harvard Medical School

2 Disclosure Information Type of Affiliation Commercial Entity Consultant/Honoraria Advance Medical FlexPharma Merck UpToDate Research Grant NIMH 1R01MH Luitpold NeuroMetrix RLS Foundation UCB

3 Most sleep problems are usually transient but 30% last > 1 year Roth et al, Biol Psych 2006

4 Sleep disorders Insomnias Insomnia, psychiatric/medical disorders, RLS, medications Hypersomnias Sleep apnea, medications, Periodic leg movements of sleep Parasomnias Sleepwalking, sleep terrors, REM sleep behavior disorder Circadian rhythm disorders Shift work sleep disorder, Delayed sleep phase disorder

5 DSM-5 Insomnia disorder Dissatisfaction with sleep quality or quantity associated with (at least one of): difficulty initiating sleep difficulty maintaining sleep early morning awakening Distress or dysfunction related to sleep disturbance Minimum of 3x/wk for 3 months The insomnia does not co-occur with another sleep disorder The insomnia is not explained by coexisting mental disorders or medical conditions

6 Chronic Insomnia Requires a Thorough Evaluation Symptoms Differential Diagnosis Treatment Diagnosis

7 Sleep quality is only as strong as the weakest link and many insomniacs have many sleep-related issues Psychiatric Illness(es) Primary Sleep Disorder(s) Medical Illness(es) Medication(s) Poor sleep Hygiene/stress All contributing factors must be treated to achieve maximum benefit

8 Differential diagnosis of chronic insomnia Primary psychiatric disorders Medications Substances Restless Legs Syndrome (RLS) Sleep schedule disorders Obstructive sleep apnea Medical disorders

9 Common cognitive and behavioral issues which can produce/worsen insomnia (cause or consequence of insomnia?) Inconsistent bedtimes and wake times Dozing in evening before bed Excessive time in bed squeezing out more sleep Sleep-related anxiety (insomniaphobia) Unrealistic expectations of total sleep time, onset and maintenance of sleep Clock watching Use of electronics in bedroom Inappropriate attributions of daytime issues to sleep

10 All psychiatric disorders produce insomnia Mania > Schizophrenia > Depression and Anxiety Disorders

11 However, psychiatric disorders are present in only 30-40% of those with insomnia Drug Abuse Other Psychiatric Disorder Alcohol Abuse Dysthymia 4.2% 5.1% 7.0% 8.6% Major Depression 14.0% Anxiety Disorders No Psychiatric Disorder 23.9% 59.5% % of Respondents Ford DE, Kamerow DB. JAMA. 1989;262:

12 Independent treatment of insomnia in major depression improves depression treatment outcome

13 Sleep disturbance is the most common persistent symptom in treated MDD Percentage of Subjects Subthreshold Threshold 0 Mood Interest Weight Sleep Psychomotor Fatigue Guilt Concentration Suicidal Ideation Symptoms **25% had treatment-emergent onset of nocturnal awakenings (Nierenberg et al, 2012)** MDD = Major depressive disorder. Nierenberg AA et al. J Clin Psychiatry

14 Persistent insomnia in treated MDD: sleep disorder or mood disorder? Major Depressive Disorder Fatigue Loss of interest Sleep disturbance Depressed mood Impaired concentration Worry Agitation Irritability Suicidality Insomnia inadequately treated MDD treatment-induced insomnia pre-existing independent (or primary) insomnia combination of above

15 PTSD is a disorder with an essential difficulty maintaining states of decreased vigilance PTSD will therefore nearly always interfere with sleep Specific questions as to the circumstances of traumatic episodes (eg night, bedroom) may shed light on sleep disturbance Treatments: - education as to relationship of PTSD to sleep disturbance - safety of sleep environment - judicious use of hypnotics - prazosin or Image Rehearsal Therapy for nightmares

16 INSOMNIA RELATED TO MEDICATIONS Antidepressants Stimulants Steroids, bronchodilators Decongestants Dopaminergic antagonists (akathisia)

17 Stimulant pharmacokinetics are not kind to sleep Adderall 20 XR Adderall 30 XR 30 mg XR IR

18 Insomnia in the elderly is not related to age, but to medical illness Cardiac: angina, PND Pulmonary: COPD, coughing GI: Nocturnal reflux Musculoskeletal pain Endocrine: Hypo/ hyperthyroidism, diabetes, menopause Neurologic: Dementia, Parkinson s, CVA, migraine Urinary: Nocturia, renal failure

19 LICIT SUBSTANCES Caffeine Sleepiness can overcome stimulant effects, but awakenings are common Alcohol produces 3-4 hours of good sleep, followed by increased wakefulness in 2nd half of night

20 Treatment of RLS Modify reversible causes Iron Deficiency (keep Ferritin > 50) Medication-Induced (SRIs, DA antagonists, antihistamines) Pharmacologic approaches Dopaminergic agonists (pramipexole, ropinirole, rotigotine patch) but watch for iatrogenic worsening of RLS ( augmentation ) Alpha 2 delta ligands (gabapentin, pregabalin) Opioids (oxycodone, methadone)

21 Sleep schedule disorders Delayed Sleep Phase Syndrome Most common in adolescents Initial insomnia and difficulty awakening in AM Daytime sleepiness Advanced Sleep Phase Syndrome Most common in the elderly Early AM awakening

22 Conditioned insomnia is present to some degree in all with chronic insomnia Many people with insomnia have negative associations and anxiety regarding sleep initiation ("insomnia phobia") which perpetuate insomnia

23

24 Winkelman JW. Insomnia Disorder. New England Journal of Medicine, 2015

25

26 The complex neurochemistry of sleep provides many treatment options Ascending arousal pathways Descending inhibitory pathways

27 Pharmacologic Treatments for Insomnia Benzodiazepine receptor agonists (BzRAs) Melatonin agonists Orexin antagonist Sedating antidepressants Anticonvulsants Dopaminergic antagonists (eg antipsychotics) Miscellaneous (eg prazosin, clonidine, hydroxyzine)

28 Medications Commonly Used for Insomnia (MCUFI) Hypnotic usage: NHANES, % of US population (estimate) Any MCUFI Zolpidem Use during the the past month: 55% of hypnotic users took 1 other sedating medication (e.g. opioids, BzA) 10% took 3 other sedating medications 19.2% said they took 1 ANY sleep medication, OTC or other Trazodone Benzo Quetiapine Doxepin N = 32,328 Age: 20 y/o Bertisch SM, et al. Sleep. 2014

29 Benzodiazepine-Receptor Agonists (BzRA) Commonly Used as Hypnotics Agent (brand name) Dose range Half-life Clonazepam (Klonopin) mg 40 hr Temazepam (Restoril)* mg 4-18 hr Lorazepam (Ativan) mg hr Oxazepam (Serax) mg 5-10 hr Eszopiclone (Lunesta) 1-3 mg hr Triazolam (Halcion)* mg 2-3 hr Zolpidem (Ambien) mg 2-3 hr (CR extends duration of action) Zaleplon (Sonata) 5-10 mg 1-2 hr *FDA approved for insomnia.

30 Do z-drugs work for insomnia? Effects modified by higher dose, younger age, female sex Huedo-Medina et al, BMJ, 2012

31 Do benzodiazepines work for insomnia? Buscemi et al, JGIM, 2007

32 Are sleeping pills addictive? Substance use disorders occur when their recurrent use causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. - DSM 5 Tolerance Physiological dependence Psychological dependence Non-medical diversion

33 The Current Status of BzRA Risks in the Treatment of Insomnia Motor vehicle accidents in elderly: long T 1/2 agents Hip fractures in elderly: long T 1/2 agents? Anterograde amnesia: T 1/2 dependent Abuse: rarely seen outside of drug abusers Tolerance: no evidence from recent 12- and 26-week studies Rebound insomnia: depends upon dose, duration of use, and speed of taper Hemmelgarn B et al. JAMA. 1997;278: Cumming RG, Le Couteur DG. CNS Drugs. 2003;17: Woods JH, Winger G. Psychopharmacology. 1995;118: Krystal AD et al. Sleep. 2003;26:

34 Benzodiazepines do increase risk for dementia Billioti de Gage et al, BMJ, 2014

35 Benzodiazepines do not increase risk for dementia Gray et al, BMJ, 2016

36 Benzodiazepines do not increase mortality risk Patorno et al BMJ 2017: Conclusions This large population based cohort study suggests either no increase or at most a minor increase in risk of all cause mortality associated with benzodiazepine initiation. If a detrimental effect exists, it is likely to be much smaller than previously stated and to have uncertain clinical relevance. Residual confounding likely explains at least part of the small increase in mortality risk observed in selected analyses.

37 Orexin antagonist in thetreatment of Insomnia Suvorexant Advantages: little abuse liability, 1-year efficacy data (at 40 mg), few side effects Disadvantages: unclear efficacy vs BzRAs, prior authorization/expense

38 Antidepressants in thetreatment of Insomnia Mirtazapine, Trazodone, Amitriptyline, Doxepin Advantages: little abuse liability Disadvantages: probably not as effective as BzRAs, daytime sedation, weight gain, anticholinergic side effects, switch into mania in bipolar disorder

39 Atypical Antipsychotics in the Treatment of Insomnia Quetiapine Advantages: anxiolytic, mood stabilizing in bipolar disorder, little abuse liability Disadvantages: less effective than BzRAs, daytime sedation, weight gain, risks of extrapyramidal symptoms and glucose + lipid abnormalities

40 Anticonvulsants in the treatment of Insomnia Gabapentin Advantages: little abuse liability, efficacy in ETOH Disadvantages: less effective than BzRAs, cognitive impairment, daytime sedation, dizziness, weight gain

41 Issues with Non-BzRA Hypnotics in the Treatment of Insomnia (eg antidepressants, anticonvulsants, antipsychotics) Paucity of short-term efficacy data Absence of long-term efficacy data Assumptions of lack of tolerance and rebound insomnia are unsubstantiated Anecdotally less effective hypnotics than BzRAs May have deleterious side effects

42 Sleep disorders Insomnias Insomnia, psychiatric/medical disorders, RLS, medications Hypersomnias Sleep apnea, medications, Periodic leg movements of sleep Parasomnias Sleepwalking, sleep terrors, REM sleep behavior disorder Circadian rhythm disorders Shift work sleep disorder, Delayed sleep phase disorder

43 Differential diagnosis of hypersomnia Tired : excessive daytime sleepiness (EDS) fatigue apathy If EDS: inadequate sleep time impaired sleep quality (eg OSA) excessive sleep drive (eg medications, narcolepsy)

44 Insomnia is more common than daytime sleepiness in those with sleep apnea Bjornsdottir et al Sleep 2013

45 Indications for Home Sleep Testing or polysomnography Suspicion of sleep apnea (loud snoring PLUS one of the following): daytime sleepiness witnessed apneas refractory hypertension Abnormal behaviors or movements during sleep Unexplained excessive daytime sleepiness Refractory sleep complaints, particularly repetitive brief awakenings

46 Physical exam (kind of) predicts likelihood of sleep apnea

47 Berlin questionnaire (kind of) predicts sleep apnea

48 OSA treatments Positive Airway Pressure (PAP) Auto-PAP allows both diagnostic and titration to be performed in the home (no sleep lab necessary) Weight loss, upper airway surgery, positional treatment

49

50 CPAP for obstructive and central sleep apnea: cardiovascular conclusions Drager et al, 2017, Circulation

51 CPAP for OSA: effects on sleepiness, mood and quality of life

52 Reflection Key Points: Treatment of chronic insomnia and excessive daytime sleepiness first requires thoughtful differential diagnosis Cognitive-behavioral therapy is first-line treatment for insomnia There are many available medication therapies for insomnia, and a detailed discussion of their benefits and risks is indicated Next Best Steps: Ask all patients if they are satisfied with their sleep Make a separate appointment to discuss sleep problems and their causes Home sleep testing is indicated for those with a suspicion of sleep apnea