Insomnia Presentation

SLEEP and INSOMNIA Lynn N. Stewart, M.D. Travis County Wellness and Health Clinic Austin, TX

Objectives By the conclusion of this lecture, you will be able to: Learn about the process of sleep Identify 4 main categories of insomnia Classify insomnia by stage List at least 5 common etiologies of insomnia Discuss 5 or more principles of sleep hygiene Give 5 guidelines for drug therapy

Why do we care about sleep? Sleep is a necessary restorative process that affects all aspects of functioning. Sleep is an active process for the brain. Early in sleep slow-rolling eye movements occur (non-rapid eye movement). Later—deeper in sleep–rapid eye movements (REM) are associated with irregular breathing and increased heart rate

Sleep Stages and their function Non-rapid Eye Movement (NREM) Stage 1: transition to sleep 5% total time Stage 2: 50% total time Stages 3 and 4: slow-wave sleep 10-20% total sleep time Restful and restorative sleep achieved here Rapid Eye Movement (REM) 20-25% total sleep time

Sleep Cycle and Architecture Normal, healthy people start with NREM1 then NREM 2, 3, 4, 3, 2, and then REM. Cycle repeats at 90-120 minute intervals Total cycle repeats 3-4 times a night NREM 3 and 4: more prominent is first half of the night, and decrease later on. REM: less prominent in the early night, and increases as the night progresses

Sleep at different ages Sleep varies with age Infants sleep 66% of the day; adults, 33% Elderly have a reduction in the depth, intensity , and continuity of sleep: Increased sleep latency Decreased REM latency Reduced NREM 3 and 4 Reduced total REM amount Frequent awakenings

So what keeps us awake? The Reticular Activating System (RAS) of the brain plays is mostly responsible for keeping us awake and alert. Narcolepsy is a clinical syndrome of daytime sleepiness with cataplexy (bilateral muscle weakness leading to partial or complete collapse), hypnagogic hallucinations, and sleep paralysis, and is associated with disordered REM sleep. Not all are required for the syndrome. A loss of orexin and hypocretin neuropeptides is typically found.

Types of Insomnia Is the problem not being able to fall asleep? -> Problems falling asleep are referred to as problems with “sleep latency.” Is the problem staying asleep? -> Problems staying asleep are referred to as problems with “sleep maintenance.”

Why Are We Talking About This? Up to 40% of adults are affected 1/3 adults are affected intermittently 10% are chronic Treatment alone costs $2-11 billion Total financial impact: $35 billion Morin CM, Hauri PJ, Espie CA, et al. Nonpharmacologic treatment of chronic insomnia: an American Academy of Sleep Medicine Review. Sleep. 1999;22:1134-1156 Silber MH. Chronic insomnia. N Engl J Med. 2005;353:803-810 Saul S. Record sales of sleeping pills are causing worries. New York Times. Feb 7, 2006.

Definition The subjective experience of inadequate or poor quality sleep “I’M UP” I - difficulty I nitiating sleep M - difficulty M aintaining sleep U - U nrefreshing sleep P - P remature awakening

Daytime Consequences Tiredness and lack of energy Poor concentration and performance Irritability and/or depression Feeling unwell Less able to enjoy life Increased illness

Real Consequences Absenteeism Presenteeism Social disability Increased healthcare utilization Fewer promotions Auto accidents Insomniacs have 2.5x more accidents due to fatigue Depression

Real Consequences Sleep deprivation (less than 6 hours of sleep a night) is an independent predictor of future weight gain AND obesity in women. RR=1.32 for gaining >15kg (>33#) over 16 years for those who sleep 5 hours/night; RR=1.12 for 6 hours/night when compared against those who slept 7 hours/night (after adjusting for exercise and caloric intake). Worcester, Sharon. “Sleep duration, weight gain are linked in women,” Family Practice News 36 (15 Oct 2006):44.

Sleep Deprivation Inadequate opportunity for sleep Feel sleepy during the day insomniacs typically feel tired, not sleepy Fall asleep at inappropriate times Such as while driving, at work during an interview, while at family events.

Hyper Arousal State from Insomnia Increased (short-term only) : Metabolic rate Heart rate Temperature Catecholamine metabolites Stress hormone levels Fast EEG activity (electrical recording of brain activity=Electro Encephalo Gram)

Risk Factors for Insomnia Prior episode Female gender (1.3x) Age > 65 (1.5x) half the population over age 65 40% of all hypnotic scripts Snoring Depression (which comes first?) Lower socioeconomic status Divorce / Separation Widowhood Concurrent medical problems

Stages of Insomnia Transient: < 4 nights (days to weeks) Acute: > 2 nights a week for 2 weeks Chronic: 3 or more nights a week, for 4 or more weeks (months to years) Critical: The inability to sleep during lectures

Psychiatric Causes of Insomnia Depression Generalized Anxiety Disorder Stress Post Traumatic Stress Disorder Obsessive Compulsive Disorder Adjustment disorders Personality disorders Bipolar disorder Dysthymia Anxiety Psychosis including schizophrenia

Medical Causes of Insomnia Pain Neuropathy Fibromyalgia Osteoarthritis Rheumatoid arthritis Chronic back pain Cardiovascular Congestive heart failure Dyspnea Nocturnal angina Pulmonary COPD Asthma Obstructive Sleep apnea Mixed Sleep apnea Obesity-hypoventilation Syndrome Gastrointestinal GastroEsophageal Reflux Disease (GERD)

Medical Causes of Insomnia Genitourinary Benign Prostatic Hypertrophy Nocturia Incontinence Endocrine/Metabolic Hormonal disruptions Menopause Thyroid disease Endocrine hormone-secreting tumors Neurologic Alzheimer’s Huntington’s Parkinson’s Central Sleep apnea Seizures Headaches (cluster, migraine) Fatal Familial Insomnia (yes, it is fatal, and familial) You’d already know about it if it is in your family

Dyssomnia Dyssomnias are sleep disorders characterized by insomnia, excessive sleepiness, or abnormal sleep-wake timing Sleep Disorders Restless Legs Trouble falling asleep Patient very aware of movement/sensations Periodic Limb Movement Disorder Unrefreshing sleep, hypersomnia Leg contractions during stages 1 & 2 Patient usually unaware of movement

Intrinsic Dyssomnia Psychophysiological insomnia Sleep state misperception Idiopathic insomnia Narcolepsy Hypersomnia Recurrent, idiopathic, post-traumatic Restless legs syndrome Obstructive sleep apnea syndrome Central sleep apnea syndrome Central alveolar hypoventilation syndrome Periodic limb movement disorder Intrinsic sleep disorder NOS

Extrinsic Dyssomnia Inadequate sleep hygiene Environmental sleep disorder Altitude insomnia Adjustment sleep disorder Insufficient sleep syndrome Limit-setting sleep disorder Sleep-onset association disorder Food allergy insomnia Nocturnal eating (drinking) syndrome Hypnotic-dependent sleep disorder Stimulant-dependent sleep disorder Alcohol-dependent sleep disorder Toxin-induced sleep disorder Extrinsic sleep disorder NOS

Circadian Dyssomnia Time zone change (jet lag) syndrome Shift work sleep disorder Irregular sleep-wake pattern Delayed sleep phase syndrome Advanced sleep phase syndrome Non-24-hour sleep-wake disorder Circadian rhythm sleep disorder NOS Shifts with age (adolescent or elderly)

Parasomnias Parasomnias are sleep disorders characterized by abnormal behavioral or physiological events which occur during sleep or during sleep-wake transitions. Parasomnias typically do not cause insomnia or excessive sleepiness, but some are dangerous to the patient or others. Most are “normal” if done while awake More common in children than adults Most do not require therapy

Parasomnias Continued Arousal disorders: Confusional arousals Sleepwalking Sleep terrors Sleep-wake transition disorders: Rhythmic movement disorder Sleep starts Sleep talking Nocturnal leg cramps Parasomnias usually associated with REM sleep: Nightmares Sleep paralysis Impaired sleep-related penile erections Sleep-related painful erections REM sleep-related sinus arrest REM sleep behavior disorder

Parasomnias Continued Parasomnias NOS Sleep bruxism (tooth grinding) Sleep enuresis (bed-wetting) Sleep-related abnormal swallowing syndrome Nocturnal paroxysmal dystomia Sudden unexplained nocturnal death syndrome Primary snoring Infant sleep apnea Congenital central hypoventilation syndrome Sudden infant death syndrome Benign neonatal sleep myoclonus Other parasomnia NOS

Pharmacologic Causes of Insomnia Antidepressants Steroids Decongestants Caffeine Coffee, tea, chocolate Alcohol Nicotine Antihypertensives Anticholinergics Hormones Antineoplastics CNS stimulants Miscellaneous Dilantin, sinemet

Behavioral Causes Poor sleep hygiene (more later) Psychophysiologic Learned behavior Worring about getting to sleep/ trying too hard to sleep Leads to increased anxiety and arousal Perpetuates insomnia

Diagnosis The medical interview is everything focus on underlying causes Sleep partner should be present for the interview if possible Full medication list is required Be prepared to ask very direct questions about substances and alcohol use

Medical Interview Current state of complaint Onset, duration, frequency of insomnia Sleep history… is the trouble with: falling asleep? maintaining sleep? not being able to go back to sleep once up? early awakenings? not feeling rested?

Medical Interview Daytime consequences can you function/stay awake to drive? Do you experience (or bed-partner report): Leg or arm jerking while asleep? Loud snoring/gasping/choking, or stopping breathing when asleep? Uncomfortable feelings in your legs that go away with moving them?

Sleep Habits Usual bedtime Usual morning awakening time Time spent in bed awake prior to sleeping, and following the onset of sleep Estimated time spent asleep Do you take anything to make you sleep? Do you drink to help you go to sleep? What else do you do in your bedroom?

Sleep Habits Anything disruptive to sleep? Infants Noises Lights Snoring partner Partner with different bed/wake times TV Pets Not feeling safe where you sleep

Sleep Habits (bad!) Do you consume: nicotine, caffeine, alcohol, other stimulants, decongestants prior to bedtime? Half lives are important! t 1/2 nicotine = 1 hour, t 1/2 caffeine = 6 hours, t 1/2 alcohol depends on how much you’ve had Do you smoke/eat when you wake up, or perform other tasks like cleaning? Do you check the clock when you wake up? What is your pre-bedtime routine: exercise, work, TV, eating?

Half-lives: why you can’t go to sleep at 10pm if your last coffee was at noon.

What’s New With You? Medical issues Medication changes Lifestyle issues Work stress School stress Financial stress Relationship changes/stress Complaints from partner

Physical Exam For primary insomnia there are no characteristic exam findings Evaluate for symptoms/findings that suggest an underlying explanation

Sleep Diaries Usually kept daily for 1-2 weeks Help delineate variability in sleep from day-to-day May identify contributing factors May help patient more accurately perceive sleep

Sleep Diaries Bedtime Time to sleep onset Number of awakenings Time out of bed in morning Total sleep time (estimated) Use of sleep medications or other substances Quality of sleep Daytime symptoms Caffeine log Exercise log

Example Sleep Patterns 6.0 hours Yes 2+ 45 Depression Or anxiety ~5.5 hours 7.5 hours Total Time Asleep Yes No Early Morning Awakenings 6 2 Awakenings 45 10 Sleep onset (minutes) Insomnia Normal

Treatment Goals Alleviate underlying problems Prevent progression from acute to chronic Improve quality of life Treat depression Treat medical conditions Limit all medications whenever possible

Acute Insomnia Often does not require treatment Should be treated when: Daytime consequences warrant treatment Episodes last more than a few days Episodes become predictable Treating acute insomnia may help promote sleep hygiene Get a sleep diary from the patient

Chronic Insomnia Usually requires many different approaches Treat underlying condition first May need behavioral and pharmacologic therapy Treatment should be collaborative Get a sleep diary from the patient

Sleep Hygiene Hygiene: from where is the term derived? Hygeia (also Hygea, Hygia, Hygieia) This is derived from the name of the Greek goddess of health known as Hygeia the daughter of Aesculapius/Asklepios and sister to Panacea. While her father and sister were connected with the treatment of existing disease Hygeia was regarded as being concerned with the preservation of good health or the prevention of disease.

Sleep Hygiene--Basics Don’t spend excessive time in bed, including daytime napping. Get into bed when sleepy. Maintain a regular sleep/wake schedule Bed is for sleep and sex only, not TV! Increase exercise and fitness Avoid caffeine and nicotine at least 4-6 hours before going to bed.

Sleep Hygiene--Basics Never use alcohol to go to sleep. It induces sleep, but causes frequent awakenings Decreases REM sleep, increases stages 3 & 4 Chronic use causes insomnia, which can persist up to a year after cessation of all drinking Avoid excessive liquids or a heavy meal in the evening. Minimize noise, light, and temperature extremes during sleep. Move alarm clock away from bed if it is distracting

Sleep Hygiene--Relaxation Plan a relaxation period before bed, develop a bedtime routine. Attempts to address somatic and cognitive arousal Relaxation Therapy: Progressive muscle relaxation EMG Biofeedback Meditation Imagery training Self-hypnosis Diaphragmatic breathing

Sleep Hygiene—Sleep Restriction If unable to fall asleep within an acceptable amount of time (15-20 min), leave the bedroom, engage in a relaxing activity until sleepy, and then return to bed. This is called sleep restriction Repeat as necessary. Boring activities (reading the phone book) count. TV/video games doesn’t count as relaxing or boring—the flashing lights stimulate the brain.

Sleep Hygiene—Sleep Restriction Sleep Restriction Therapy Track average total sleep time per night Spend only this amount of time in bed; minimum being 4.5 hours. Once 90% of time in bed is spent asleep (sleep efficiency), increase total time in bed by 15 minutes every 5-7 days.

Sleep Hygiene—Sleep Restriction If sleep efficiency falls to less than 80%, decrease time in bed by 15 minutes Work set, daytime hours (whenever possible). As sleep consolidation improves, time in bed (and asleep) increases. Creates a mild state of sleep deprivation, and thus promotes more rapid sleep onset and more efficient sleep.

Sleep Hygiene—Cognitive Therapy Cognitive Therapy works to change beliefs about insomnia: Misconceptions about the causes Performance anxiety and loss of control over the ability to sleep Unrealistic sleep expectations Identify and replace dysfunctional beliefs and attitudes about sleep For example, questioning the idea that you must sleep 8 hours to function effectively

Behavioral Therapies Reliable and enduring improvements for chronic insomniacs Sleep latency insomniacs fell asleep faster than 81% of untreated controls Sleep maintenance insomniacs slept longer than 74% of untreated controls May be used in combination with other techniques or medications

Stimulus Control Therapy Based on premise that insomnia is a conditioned response based on cues associated with sleep Trains the brain to associate the bed / bedroom with sleep Leave the bedroom if not sleeping within 15-20 minutes Effective for sleep onset and sleep-maintenance

Other Therapies Regular exercise Helpful if timed in the late afternoon Any exercise, regardless of time of day, helps Promotes sleep depth and quality May be stimulating if done in closer to bedtime Phototherapy Exposure to daytime bright light is helpful in treating those with slow or fast circadian cycles May be especially helpful in the elderly

What works best? Multicomponent cognitive behavior therapy works better than both placebo and pharmacotherapy (medicines) in short and long term cases. Jacobs GD, Pace-Schott EF, Stickgold R, et al. Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Intern Med . 2004; 164: 1888-1896 Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Psychiatr . 1994; 151: 1172-1180. Murtagh DR, Greenwood KM. Identifying effective psychological treatments for insomnia: a meta-analysis. J Consult Clin Psychol . 1995; 63:79-89.

If you have to use drugs: Pharmacotherapy Guidelines Use the lowest therapeutic dose Use for the shortest duration necessary Discontinue medication gradually Be alert for rebound insomnia Use agents with short half-lives to minimize daytime sedation

Drugs that make you sleep Drugs that make you sleep are called “hypnotics”. There are many types of hypnotics: Sedating antihistamines (over the counter) Herbals (over the counter) Benzodiazepines (prescription/controlled) Benzodiazepine-Like (prescription/controlled) Melatonin receptor agonists (prescription) Antidepressants (prescription) Antipsychotics (prescription)

Over the Counter Medicines—FDA approved and regulated Sedating antihistamines: diphenhydramine (Benadryl) and doxylamine Nighttime Sleep Aid Sleep Aid Liqui-Gels Maxium Strength Unisom Nighttime Sleep Aid Tylenol PM

OTC Medicines—FDA approved and regulated Sedating antihistamines continued: Not addictive, but tolerance develops quickly Daytime sleepiness, anticholinergic side effects common Dry mouth, constipation, urinary retention, memory impairment, confusion (dries up sinuses if post nasal drip is what keeps you up)

OTC Medicines--herbals Not FDA regulated: Valerian root Used for anxiety, and as a sleep aid Dosing uncertain Powerful odor Kava-kava Can cause liver failure Dosing uncertain Sateia MJ, Nowell PD. Insomnia. Lancet . 2004; 364:1959-1973

OTC Medicines--herbals Melatonin—hormone made by the pituitary gland in the brain (at night/when dark) Best for shift work/jet lag; shifts sleep to dark hours Schenck CH, Mahowald MW, Sack RL. Assessment and management of insomnia JAMA 2003;289:2475-2479. For insomnia not related to shift work/jet lag, there is NO convincing evidence it works. Silber MH, Chronic insomnia. N Engl J Med. 2005;353:803-810 Almeida Montes LG, Ontiveros Uribe MP, Cortez Sotres J, et al. Treatment of primary insomnia with melatonin: a double-blind, placebo-controlled, crossover study. J Psychiatry Neurosc. 2003; 28: 191-196

Prescription Medicines: Benzodiazepines Non-selectively bind to the benzodiazepine-GABA (Gamma-AminoButyric Acid) receptor complex in the brain Effective in inducing, maintaining, and consolidating sleep; and in decreasing daytime consequences of insomnia

Prescription Medicines: Benzodiazepines Side effects include daytime drowsiness, anterograde amnesia, impairments in memory and psychomotor performance. Addiction, habituation, tolerance, rebound insomnia, withdrawal symptoms, anxiety can all occur with benzo use When combined with alcohol, benzodiazepines can be deadly. Increases fall risk in the elderly (and concomitant hip fractures)

Prescription Medicines: Benzodiazepines No one medicine in the class works any better than any other medicine. Those with a short half-life work better for those who have trouble falling asleep Those with a longer half-life work better for those who cannot stay asleep No benzodiazepine is FDA approved for chronic use (think vioxx)!

Presciption Medicines: Benzodiazepines—how they work Generic name (brand)--duration/onset of effects used for Triazolam (Halcion) – short/rapid sleep onset insomnia; pregnancy category X Estazolam (ProSom) – intermed/rapid both sleep onset and maintenance insomnia; preg category X Temazepam (Restoril) – intermed/slow Sleep maintenance; pregnancy category X Flurazepam (Dalmane) – long/intermed Sleep maintenance—active metabolite for over 100 hours; X Quazepam (Doral) – long/intermed Sleep maintenance—active metabolite for over 100 hours

Prescription Medicines: Benzodiazepine Information 10-15% of users take them regularly for more than a year (not FDA approved) Many patients (not all) develop physical dependence and/or tolerance Once an effective dose is established, higher doses typically only increase side effects Sudden withdrawal can be dangerous to the patient

Prescription Medicines: Benzodiazepine Contraindications Pregnant women (most are category X) Untreated sleep-related breathing disorder Alcohol or substance abuse Patients who might need to awaken and function during their normal sleep period Parents, doctors, fire-fighters, etc. Monitor those with hepatic, renal, or pulmonary disease; and use with caution

Prescription Medicines: Benzodiazepine-Like Benzodiazepine-Like medicines selectively bind to the benzo-GABA receptor. The benzos we learned about before are non-selective; there should be fewer side effects with the Benzo-Like meds than true benzos. Exact mechanism of action is unknown Help people go to sleep (sleep latency), and stay asleep (sleep maintenance).

Prescription Medicines: Benzodiazepine-Like Eszopiclone (Lunesta)—intermed/rapid Sleep maintenance (metallic taste); pregnancy category C Zolpidem (Ambien)—short/rapid Sleep latency; side effects include: sleepwalking, sleep-related eating disorder; pregnancy category B (?C) Zolpidem controlled release (Ambien CR)—intermed/rapid Sleep latency, sleep maintenance; pregnancy category C Zaleplon (Sonata)—ultrashort Sleep latency, can take in the middle of the night if you awaken; pregnancy category C

Prescription Medicines: Benzodiazepine-Like Zolpidem (Ambien) and Zaleplon (Sonata) Zolpidem t ½ = 2.5 hours; no residual effects if taken 5 hours before awakening; works well for freq. awakenings; Preg. B, and generally regarded safe in nursing Zaleplon t ½ = 1 hour; no residual effects if taken > 2 hours before awakening; works well for terminal insomnia; Preg. C Relatively new = relatively expensive

Prescription Medicines: Melatonin-Receptor Agonist Ramelteon (Rozerem)—short duration: 1-2.5 hrs Sleep latency, not sleep maintenance may increase prolactin levels (meaning you may lactate—typically undesired, especially in men) Dizziness, nausea, headache all common No dependence, withdrawal, or rebound insomnia! NOT a controlled substance New medicine, long-term effects unknown; pregnancy category C, activity not through GABA receptor complex Do not take after a high-fat meal

Prescription Medicines: Other Drugs (antidepressants) Amitriptyline (Elavil) Tricyclic antidepressant, inhibits norepinephrine and serotonin uptake in the CNS—pregnany category C Doxepin (Adapin) Tricyclic antidepressant, inhibits norepinephrine and serotonin uptake in the CNS—pregnancy category C Trazadone (Desyrel) sedating antidepressant (non-TCA/non SSRI)—cat. C Mirtazapine (Remeron) Sedating antidepressant, antagonizes alpha2-adrenergic and serotonin 5-HT2 receptors (tetracyclic)—pregnancy category C

Prescription Medicines: Other Drugs (antidepressants) Antidepressants only work well if patient is depressed; otherwise, trazadone and elavil work, but not as well as Ambien (Benzo-Like). Should not be used in combination as a sleep aid if the patient is taking some other form of antidepressant. Antidepressants used as sleep aids are not addicting. Antipsychotics should only be used in psychotic patients or occasionally the elderly in an institutional setting, if they cannot tolerate other medicines

If all else fails If your bed partner sleeps well, but keeps you up by snoring, moving, coughing, etc., sleep in a different bed or in a different room.

Summary Be alert for symptoms of insomnia and depression Determine specific type of sleep problem Make a differential diagnosis Don’t neglect behavioral therapies Pay attention to onset of action/duration of effect of all medicines used Teach ALL insomniacs proper sleep hygiene

References 1) AAFP and American Academy of Sleep Medicine Monograph “Strategies for Managing Insomnia” 1999 2) Roth T, Roehrs T. Insomnia: Epidemiology, characteristics, and consequences. Clin Cornerstone 2003;5(3):5-15 3) Neubauer DN. Pharmacologic approaches to the treatment of chronic insomnia. Clin Cornerstone 2003;5(3):16-27 4) Smith MT, Neubauer DN. Cognitive behavior therapy for chronic insomnia. Clin Cornerstone 2003;5(3):28-40 5) Kupfer DJ, Reynolds CF. Management of Insomnia. NEJM 1997;336:341-46

References 6) National Center on Sleep Disorders Research… Insomnia: Assessment and Management in Primary Care. NIH/NHLBI, 1998: 1-16 7) Hauri PJ. Sleep Disorders. Clinics in Chest Medicine. 1998;19:157-68 8) Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry 1997;154:1417-1423 9) Krystal AD. Insomnia in women. Clin Cornerstone 2003;5(3):41-50 10) Ward SH, Ward LD. The evaluation and management of insomnia in primary care. Patient Care . July 2006;40:46-55. 11) Gritz BF. “Overview of Insomnia” CME-TAFP Primary Care Lecture Series. Dec 6, 2006.

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