Insomnia Teofilo Lee-Chiong MD Professor of Medicine National Jewish Health University of Colorado Denver School of Medicine Learning Objectives Learn about the causes of transient and chronic Learn how to perform a thorough sleep history to evaluate patients with Learn how to individualize management of patients with Apply the principles of cognitive behavioral therapy for the treatment of Select from among the various hypnotic agents for treating patients with Disclosure Research funding: NIH, Respironics, Embla Consulting: Elsevier 1
Insomnia Repeated difficulty with either falling or staying asleep Despite adequate opportunity, condition and time for sleep Associated with impairment of daytime function Descriptions of Sleep Short and inadequate Light and easily disrupted Of poor quality Unrefreshing Not satisfying Non-restorative Descriptions of Sleep In adults: Prolonged periods of wakefulness In children: Bedtime resistance Inability to sleep independently Can t fall asleep Wake up a lot Can t fall asleep again Wake up too early Demographics Percent 70 60 50 40 30 56 67 57 44 The most common sleep disorder Occasional - 30-50% of adults Chronic - 10-30% of adults Gender: F > M 20 10 0 NSF Survey 1991 2
Risk Factors Prevalence of Insomnia Males Aging Lower socioeconomic status or unemployment Marital status (divorced or widowed) Poor health status and physical disability Medical, neurological and psychiatric disorders 40% 35% 30% 25% 20% 15% 10% 5% 0% Females 15-19 20-29 30-39 40-49 50-59 60-69 70+ Total Weyerer Dillings. Sleep 1991 Insomnia: Consequences Fatigue, reduced energy Increased risk of developing a psychiatric illness (depression) Cognitive impairment Impaired academic and occupational performance Greater healthcare use Insomnia: Classification Transient - Lasting only a few days Chronic - Persisting for more than 1-3 months Causes Numerous and diverse etiologies More than one cause may be present Identifying cause may be difficult when has been present for many years Etiology Primary sleep disturbances Circadian rhythm disorders Medical, neurological and psychiatric illnesses Medication use or withdrawal 3
Insomnia: Specific Causes Adjustment Idiopathic Inadequate sleep hygiene Paradoxical Psychophysiologic Adjustment Insomnia Sleep disturbance due to an acute stressor Momentous life event Change in sleeping environment Acute illness Sleep improves with resolution of acute stressor or with adaptation Idiopathic Insomnia No identifiable etiology Onset during infancy or early childhood Chronic life-long course Inadequate Sleep Hygiene Due to activities or behavior that increase arousal or decrease sleep propensity Activities and behavior are under a person s control Paradoxical Insomnia Sleep state misperception Subjective reports of very minimal or no sleep during most nights But normal sleep quality and architecture during PSG No daytime napping or impairment of daytime functioning Psychophysiologic Insomnia Due to heightened cognitive and somatic arousal at bedtime Rumination Increased agitation and muscle tone Anxiety is limited to issues related to sleep Learned maladaptive sleep-preventing behavior 4
Psychophysiologic Insomnia Conditioned arousal is limited to a person s own bed and bedroom Secondary Insomnia Sleep disorders Sleep disordered breathing Parasomnias Altitude Restless legs syndrome Periodic limb movement disorder Circadian Rhythm Sleep Disorders Jet lag Shift work disorder Advanced sleep phase syndrome Delayed sleep phase syndrome Jet Lag Rapid travel across multiple time zones Traveler s intrinsic circadian rhythm remains synchronized to the home time zone Westward flights - early morning awakening Eastward flights - sleep onset Shift Work Disorder Work schedules outside of traditional 8 AM to 5 PM shift Sleep time misaligned to environmental and social time cues Insomnia during morning following a night work shift Insomnia in early evening for early morning work schedules Delayed Sleep Phase Syndrome Major nocturnal sleep period occurs later than desired bedtime Inability to sleep until the early morning hours Awakening is equally late (late morning to early afternoon) 5
Advanced Sleep Phase Syndrome Major nocturnal sleep period occurs earlier than desired bedtime Habitual early sleep onset Early morning awakening (between 1-3 AM) Medical Disorders Respiratory disorders (Asthma, COPD) Cardiac disorders (Nocturnal angina, CHF) Pain syndromes Gastrointestinal disorders (GERD, PUD) Dermatologic disorders (Pruritus) Cancer Infectious disorders (HIV) Neurological Disorders Cerebral degenerative disorders Dementia Parkinsonism Sleep-related headaches Sleep-related seizures Psychiatric Disorders Alcoholism Anxiety disorders Mood disorders Panic disorders Psychoses Common Medications that can Cause Insomnia Antidepressants (fluoxetine or protriptyline) b-blockers Bronchodilators Decongestants Steroids Stimulants Insomnia: Evaluation History and sleep diary Sleep studies, actigraphy and laboratory tests are not routinely indicated Possible indications for sleep studies to exclude OSA, PLMD or paradoxical 6
Medical Interview Sleep history Duration of Timing of sleep disturbance Medical disorders Habits Medication use Nighttime activities Duration of Insomnia Transient Jet lag Shift work disorder Acute stressor/s Timing of Sleep Disturbance Sleep-onset Delayed sleep-phase syndrome Restless leg syndrome Anxiety Timing of Sleep Disturbance Recurrent awakenings Periodic limb movement disorder Obstructive sleep apnea Timing of Sleep Disturbance Early morning awakenings Advanced sleep-phase syndrome Depression Therapy of Insomnia General measures Treatment of comorbid Sleep hygiene Non-pharmacologic therapy Pharmacologic therapy 7
Sleep Hygiene Establishment of regular bedtime and arising times Avoidance of alcohol, caffeine and nicotine close to bedtime Limiting late evening stimulating activities Environmental management Cognitive Behavioral Therapy Short-term benefits are comparable to pharmacologic therapy Beneficial effects are sustained over time Cognitive Behavioral Therapy Cognitive therapy Paradoxical intention Relaxation techniques Sleep restriction Stimulus control Cognitive Therapy Addresses dysfunctional beliefs related to Irrational expectations Excessive worry Unrealistic concerns Provides a more appropriate understanding of Paradoxical Intention Decrease performance anxiety related with efforts to fall asleep Patients are instructed to go to bed and try to stay awake as long as they can Relaxation Techniques Reduction of somatic and cognitive hyperarousal Progressive muscle relaxation Biofeedback Guided imagery 8
Sleep Restriction Reducing time spent awake in bed to enhance homeostatic sleep drive Time in bed is subsequently increased once sleep efficiency improves Advance or delay bedtime based on calculated sleep efficiency Sleep Restriction If SE > 90%: Earlier bedtime If SE 80-90%: Same bedtime If SE < 80%: Later bedtime Same wake up time every morning No daytime napping Stimulus Control Strengthens the association of bedroom and bedtime to a conditioned response for sleep Use the bed only for sleep or sex Lie down to sleep only when sleepy Stimulus Control If unable to fall asleep, get out of bed and go to another room Engage in a restful activity, and return to bed only when sleepy Pharmacotherapy May enhance sleep but often do not improve daytime performance Minimal long-term beneficial effect on sleep following drug discontinuation General Recommendations Limit to short-term use at the lowest effective dose Reassess indications periodically Monitor Effectiveness of therapy Adverse reactions Self-escalation of the medication dose Changes in medical or psychiatric status 9
General Recommendations Inform patients of benefits and risks of hypnotic use Use with caution in patients with significant respiratory, renal and hepatic impairment Avoid use during pregnancy Avoid taking with alcohol Pharmacotherapy Insufficient evidence regarding efficacy of Sedating antipsychotic agents Antihistamines Botanical compounds Elimination Half-lives of Hypnotic Agents Selection of Hypnotic Agents Less than 1 hour Zaleplon 2 to 5 hours Eszopiclone Triazolam Zolpidem 5 to 24 hours Estazolam Temazepam Greater than 40 hours Flurazepam Quazepam Short-acting agents - for sleep-onset Ramelteon and zaleplon Intermediate-acting agents - for concurrent sleep-onset and sleep-maintenance Benzodiazepines, eszopiclone and zolpidem Selection of Hypnotic Agents Long-acting agents - for early morning awakenings and daytime anxiety Benzodiazepines Benzodiazepine Receptor Agonists Bind to the gamma-aminobutyric acidbenzodiazepine (GABA-BZ) receptor complex 1 0
Benzodiazepines Bind non-selectively to the different GABA- BZ receptor subunits Properties Hypnotic Anxiolytic Myorelaxant Anticonvulsant Adverse Effects of Benzodiazepines Rebound daytime anxiety Daytime sleepiness Cognitive and psychomotor impairment Development of tolerance Adverse Effects of Benzodiazepines Withdrawal symptoms - anxiety, irritability and restlessness Rebound Respiratory depression and worsening of OSA Increase in falls - in some older adults Dependency and abuse liability (low risk) Non-Benzodiazepine Benzodiazepine Receptor Agonists Compared to conventional benzodiazepines Similar hypnotic action No muscle relaxant, anticonvulsant or anxiolytic properties Less likely to cause rebound, withdrawal symptoms or tolerance Less likely to alter sleep architecture Melatonin Receptor Agonist Ramelteon Selective agonist for the SCN melatonin receptor Short half-life - indicated for sleep-onset Contraindications - use of fluvoxamine and hepatic impairment Other Hypnotic Agents Melatonin Used primarily for associated with circadian rhythm sleep disorders Short half-life of 20-30 minutes 11
Summary Sleep disturbance is common Adversely affects QOL Cause is often multi-factorial Diagnosis require high clinical suspicion Treatment should be individualized 1 2