Insomnia

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Insomnia

• Victoria E Judd M.D.

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Sleep Quotes

• People who say they sleep like a baby usually
  don't have one.  Leo J. Burke
• If people were meant to pop out of bed, we'd all
  sleep in toasters.  Author unknown

• O sleep, O gentle sleep,Nature's soft nurse, how
  have I frighted thee,That thou no more wilt
  weigh my eyelids downAnd steep my sense in
  forgetfulness?William Shakespeare, Henry IV,
  Part I

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Insomnia

• No disclosures

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Objectives

• Learn about sleep
• List pathogenesis/types of insomnia
• Discuss epidemiology of insomnia
• Learn about the impact of insomnia
• List common etiologies of insomnia
• Discuss therapy
• -Cognitive-behavioral therapy
• -Pharmacologic treatment

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Sleep Is

• Active
• Complex
• Highly Regulated
• Involves different areas in the brain
• Purpose is not understood
• Essential to life/necessary
• We all do it

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Sleep Deprivation

• Our 24/7 lifestyle can be deleterious
• Trying to push through the night and stifle a
  yawn, yet that yawn is the first sign that youre
  not so awake as you might like to think after
  18 hours in the absence of sleep, your reaction
  time slows from ¼ of a second to ½ of a second,
  and then becomes still longer

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Sleep Deprivation

• One starts experiencing several bouts of
  micro-sleep and so, while driving you zone
  out for say 20 seconds and drift out of your
  lane, or if studying late then you find yourself
  rereading the same passage thus your reaction
  time becomes roughly equivalent to a person with
  a blood alcohol level of 0.08, sufficient to get
  you arrested in 49 states

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Sleep Deprivation

• Charles Augustus Lindbergh, in 1927, in his
  Spirit of St. Louis, during his 1st solo Atlantic
  crossing from Long Island to Paris, experienced
  visual hallucinations which remitted with
  recovery sleep
• There is a 10 increase in MVAs following
  switching to daylight savings when the day is
  shortened by 1 hour

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Consequences of Insomnia
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Sleep Deprivation

• Mood disturbance with irritability, transient
  paranoia, disorientation, performance deficits,
  severe fatigue or hypomania all sequelae of
  prolonged sleep deprivation
• Chronic sleep deprivation may reach a point at
  which the very ability to catch up on sleep is
  damaged, such that whats lost is lost
• Bodes ill for students, soldiers, et. al, trying
  to acquire new information while sleep-deprived

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Sleep Disorders

• Sleep disorders are common
• Sleep disorders are serious
• Sleep disorders are treatable
• Sleep disorders are underdiagnosed

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Sleep

• Sleep Stages
• Stage 1- transition to sleep, 5 of total time
• Stage 2- 50 of total time
• Stage 3 4- Most restorative sleep , slow wave
  sleep, 20-24 of total sleep time
• Rapid eye movement (REM)- 20-25 of total sleep
  time (When we dream)

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Sleep

• Normal sleep starts with stage 1-2-3-4-3-2-REM
• The cycle repeats at 10-120 (90) minute intervals
• There are 3 to 4 cycles a night
• Stage 3 4 are more prominent in the first half
  of the night and decrease as time goes on
• REM is less prominent in the first half of the
  night and increases as time goes by

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Sleep Cycle
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Sleep

• Sleep varies with age
• Infants sleep 66 of the day
• Young adults sleep 33 of the day
• Older adults sleep less, wake more, have less
  stage 3, 4 and REM sleep
• More REM sleep better learning in students
• The last 2 hours of REM sleep tend to be the most
  important for integrating new information

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The Need For Sleep

• Over the years, the need for REM sleep decreases
  considerably, while the need for NREM sleep
  diminishes less sharply

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Insomnia - DSM IV criteria

1. Difficulty initiating or maintaining sleep, or
   non-restorative sleep, for at least 1 month.
2. Clinically significant distress or impairment in
   social/occupational functioning
3. Not exclusively due to another sleep disorder
4. Not exclusively due to another mental disorder
5. Not due to the physiological effects of a
   substance or a medical disorder

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Insomnia

• Insomnia is present when all three of the
  following criteria are met
• A complaint of difficulty initiating sleep,
  difficulty maintaining sleep, or waking up too
  early.
• The above sleep difficulty occurs despite
  adequate opportunity and circumstances for sleep.
• The impaired sleep produces deficits in daytime
  function.

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Features of Insomnia

• Problems initiating sleep (greater than 30
  minutes)
• Frequent and/or prolonged nocturnal awakenings
• Early morning awakenings with an inability to
  return to sleep
• Poor sleep quality and sleep efficiency
• Cognitive arousal typically reported
• Severity is judged along several dimensions,
  including frequency, intensity and duration of
  sleep difficulties. Also impact on daytime
  functioning, mood and quality of life.

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Insomnia-Hyperarousal

• In experimental models of insomnia, healthy
  subjects deprived of sleep do not demonstrate the
  same abnormalities in metabolism, daytime
  sleepiness, and personality as subjects with
  insomnia. In an experimental model in which
  healthy subjects were given caffeine, causing a
  state of hyperarousal, the healthy subjects had
  changes in metabolism, daytime sleepiness, and
  personality similar to the subjects with
  insomnia.
• These results support a theory that insomnia is a
  manifestation of hyperarousal. In other words,
  the poor sleep itself may not be the cause of the
  daytime dysfunction, but merely the nocturnal
  manifestation of a general disorder of
  hyperarousability.

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Impact of Insomnia

• Biological
• Poor function of immune system
• Functional impairments
• Increased risk of accidents
• More likely to report lack of concentration and
  motivation
• Reduced productivity, work/school absenteeism
• Increased use of health care services

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Impact of Insomnia

• Psychological health
• Increases risk of developing depression,
  anxiety or substance dependence
• Risk factor in suicide
• (Ohayon et al., 1997 Harvey, 2001 Ancoli-Israel
  Roth, 1999 McCrae Lichstein, 2001)

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Impact of Insomnia

• Knutson et al found that the quantity and quality
  of sleep correlate with future blood pressure. In
  an ancillary to the Coronary Artery Risk
  Development in Young Adults (CARDIA) cohort
  study, measurement of sleep for 3 consecutive
  days in 578 subjects showed that shorter sleep
  duration and lower sleep maintenance predicted
  both significantly higher blood pressure levels
  and adverse changes in blood pressure over the
  next 5 years.

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Types of Insomnia, Time

• Transient insomnia episodic
• Acute illness
• Jet lag
• Shift change
• Short-term insomnia few days to 3 weeks
• Major life event
• Substance abuse
• Chronic insomnia longer than 4 weeks
• Chronic illness
• Psychiatric illness

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Circadian Related Insomnia, Time

• 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
• Shifts with age (adolescent or elderly)

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Chronic Insomnia

• Complaint of poor sleep causing distress or
  impairment for 1 to 6 months or longer
• Average less than 6.5 hours sleep per day
• Or 3 episodes per week of
• Taking longer than 30 minutes to fall asleep
• Waking up during the night for at least an hour
• Not accounted for by another sleep disorder,
  mental illness, medical illness or substance
  abuse.

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Types of Insomnia

• Primary insomnia
• Idiopathic insomnia Insomnia arising in infancy
  or childhood with a persistent, unremitting
  course
• Psychophysiologic insomnia Insomnia due to a
  maladaptive conditioned response in which the
  patient learns to associate the bed environment
  with heightened arousal rather than sleep onset
  often associated with an event causing acute
  insomnia, with the sleep disturbance persisting
  despite resolution of the precipitating factor
• Paradoxical insomnia (sleep-state misperception)
  Insomnia characterized by a marked mismatch
  between the patients description of sleep
  duration and objective polysomnographic findings

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Types of Insomnia

• Secondary insomnia
• Adjustment insomnia Insomnia associated with
  active psychosocial stressors
• Inadequate sleep hygiene Insomnia associated
  with lifestyle habits that impair sleep
• Insomnia due to a psychiatric disorder Insomnia
  due to an active psychiatric disorder, such as
  anxiety or depression
• Insomnia due to a medical condition Insomnia
  due to a condition such as the restless legs
  syndrome, chronic pain, nocturnal cough or
  dyspnea, or hot flashes
• Insomnia due to a drug or substance Insomnia
  due to consumption or discontinuation of
  medication, drugs of abuse, alcohol, or caffeine

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Proper 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 (OTC, Rx,
  Natural)
• Substances and alcohol use

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Interview

• Sleep historyis there trouble with
• - falling asleep?
• - maintaining sleep?
• - not being able to go back to sleep?
• - early awakenings?
• - not feeling rested?
• - daytime consequences?

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Interview

• Daytime consequences can you function/stay awake
  to drive?
• Do you experience (or bed-partner report) Leg or
  arm jerking while asleep? (periodic limb movement
  disorder)
• Loud snoring/gasping/choking, or stopping
  breathing when asleep? (sleep apnea)
• Uncomfortable feelings in your legs that go away
  with moving them? (restless leg syndrome)

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Interview

• Patients with insomnia typically feel fatigued
  during the day, but are unable to fall asleep if
  given a chance to lie down to take a nap.
• Patients with poor nocturnal sleep due to other
  sleep disorders readily fall asleep during the
  day. ( Except poor sleep hygiene.)

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Interview

• 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?

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Interview

• Anything disruptive to sleep?
• Computer
• Noises
• Lights
• Snoring partner/roommate
• Partner/roommate with different bed/wake times
• TV
• Pets
• Not feeling safe where you sleep

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Interview

• Do you consume nicotine, caffeine, alcohol,
  other stimulants, decongestants prior to bedtime?
  
• Half lives are important!
• Do you smoke/eat when you wake up, or perform
  other tasks like cleaning?
• Do you check the clock when you wake up early?
• What is your pre-bedtime routine exercise, work,
  TV, eating?

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Interview-Stimulants

• Some Common Sources
• Coffee a cup of Joe with 100-150 mg of caffeine
  1 mg of amphetamine
• Red Bull 250 mL 80 mg of caffeine
• Bakers Chocolate 1 oz 26 mg of caffeine
• Tea variable

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Interview

• Medical issues
• Medication changes
• Lifestyle issues
• Work stress
• School stress
• Financial stress
• Relationship stress
• Complaints from partner

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Stressful Life Events

• Loss of a loved one
• Divorce/Separation
• Loss of employment
• Arguments
• Particularly happy or sad events
• Work demands
• School demands
• Injuries
• Illnesses

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Medical Conditions Associated With Insomnia

• Hyperthyroidism
• Arthritis or any other chronic painful condition
• Chronic lung or kidney disease
• Cardiovascular disease (heart failure, CAD)
• Heartburn (GERD)
• Neurological disorders (epilepsy, Alzheimers,
  headaches, stroke, tumors, Parkinsons Disease)
• Diabetes
• Menopause/Menstrual disorders

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Some Medications that Cause Insomnia

• Alcohol
• Caffeine/chocolate
• Nicotine/nicotine patch
• Beta blockers
• Calcium channel blockers
• Bronchodilators

• Corticosteroids
• Decongestants
• Antidepressants
• Thyroid hormones
• Anticonvulsants
• High blood pressure medications

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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

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Types of Insomnia

• Comorbid insomnia
• Sleep disturbance is comorbid with an underlying
  problem

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Causes of Insomnia
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Epidemiology

• More than half of adults in the U.S. said they
  experienced insomnia at least a few nights a week
  during the past year
• Nearly one-third said they had insomnia nearly
  every night
• Increases with age
• The most frequent health complaint after pain
• Twice as common in women as in men

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Epidemiology

• 69 have insomnia-occasional 50 and chronic 19
  
• 35 percent insomnia during the previous year (50
  serious)
• Approximately 10 of individuals develop chronic
  insomnia with related daytime consequences

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Insomnia

• Variables associated with the onset of insomnia
  include
• a previous episode of insomnia
• a family history of insomnia
• a predisposition toward being more easily aroused
  from sleep
• poorer self-rated health
• more body pain

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CONTRIBUTING FACTORS TO DEVELOPMENT OF INSOMNIA

• Predisposing factors
• Personality
• Sleep-wake cycle
• Circadian rhythm
• Coping mechanisms
• Age
• Precipitating factors
• Situational
• Environmental
• Medical
• Psychiatric
• Medications

• Perpetuating factors
• Conditioning
• Substance abuse
• Performance anxiety
• Poor sleep hygiene

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Most Common Daytime Complaints

• Fatigue or malaise
• Poor attention or concentration
• Social, school, or vocational dysfunction
• Mood disturbance-More sadness, depression, and
  anxiety
• Daytime sleepiness
• Cognitive impairment
• School or work days missed

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Most Common Daytime Complaints

• Reduced motivation or energy
• Increased errors or accidents
• Tension, headache, or gastrointestinal symptoms
• Ongoing worry about sleep
• Risk taking behavior
• Deficits in academic performance
• Poorer Health

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Consequences of Insomnia

• The National Sleep Foundation found that students
  who reported insufficient sleep performed worse
  on tests had lower grades. Those who reported
  getting enough sleep had As and Bs.
• Thus students who are chronically sleepy may
  chose easier courses in college. Thus limiting
  their future options.

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Consequences of Insomnia

• Even though students may compensate by getting
  extra sleep on the weekend, this is not enough to
  compensate for the lost sleep during the week,
  resulting in a mounting sleep deficit.

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Consequences of Insomnia

• Worsens psychiatric disorders
• Prolongs medical illnesses
• Reduced quality of life
• Higher health care costs

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Depression and Insomnia

• Insomnia is both a risk factor for depression and
  a consequence of depression
• Could effective management of insomnia decrease
  the incidence of depression?
• Could effective management of insomnia modify the
  risk for relapsing depression?

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Insomnia Assessment

• Interview
• Physical exam
• Labs TSH Free T4, Glucose and Hgb A1C, BUN
  Cr, Iron Studies
• Psychometric
• Anxiety Depression Questionnaires
• Sleep Disorders Questionnaire

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Measures of Sleep

• Insomnia Severity Index
• Epworth Sleepiness Scale (not good for insomnia)
• Sleep Diaries
• Reports of partner

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How to keep track of your sleep

• Daily sleep diary or sleep log
• Bedtime
• Falling asleep time
• Nighttime awakenings
• Time to get back to sleep
• Waking up time
• Getting out of bed time
• Naps

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Non-drug treatments

• Cognitive-behavioral therapy (CBTI)
• Stimulus control
• Cognitive therapy
• Sleep restriction
• Relaxation training
• Sleep hygiene
• Cognitive therapy

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Insomnia - CBTI model (Espie,91)
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CBTI

• Stimulus control
• Sleep hygiene
• Sleep restriction
• Relaxation
• Paradoxical intention
• Cognitive restructuring
• Worry postponement

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• Insomnia
• Stimulus Control
• Insomnia is a conditioned response to temporal
  and
• environmental cues
• Promote consistent sleep / wake cycle
• Re-associate the bedroom with sleeping
• Well established stand alone treatment

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BEHAVIORAL TREATMENTS

• Stimulus control therapy
• Assumes that there is a learned associated
  between wakefulness and the bedroom
• To break the cycle, the patient must not spend
  time wide awake in the bedroom
• Go to bed only when sleepy
• Do not use the bedroom for sleep-incompatible
  activities
• Leave the bedroom if awake for more than 20
  minutes
• Return to bed only when sleepy
• Repeat if necessary
• Do not nap during the day
• Arise at the same time every morning

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• Insomnia
• Sleep Hygiene Education
• Factors that affect sleep, e.g. caffeine,
  alcohol, etc.
• Not primary cause of insomnia but can maintain
  problem
• Limited benefits if used alone, Not sufficient
  as a stand alone treatment
• Specific behaviors will directly interfere with
  the ability to sleep
• The behaviors can be changed with education

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Sleep Hygiene

• Having good sleep hygiene knowledge is weakly
  associated with good sleep hygiene but is not
  related to overall sleep quality.
• Practicing good sleep hygiene is strongly related
  to good sleep quality.

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Sleep Hygiene

• Fix a bedtime and an awakening time
• Avoid napping during the day
• Avoid alcohol, nicotine, chocolate before bed
• Avoid caffeine containing beverages 4 6 hours
  before bedtime
• Avoid heavy, spicy, acidic or sugary foods before
  bed
• Regular exercise is good, not before bedtime
• Comfortable bedding
• Bedroom cool, dark, quiet
• Bedroom reserved for sleep and sex NOT a work
  room

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Sleep Hygiene

• Avoid trying to sleep
• You cant make yourself sleep, but you can set
  the stage for sleep to occur naturally
• Avoid a visible bedroom clock with a lighted dial
• Dont let yourself repeatedly check the time!
• Turn the clock around or put it under the bed

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More healthy sleep habits

• Expose yourself to bright light at the right time
• Morning, if you have trouble falling asleep at
  night
• Night, if you want to stay awake longer at night
• Establish a regular sleep schedule
• Get up at the same time 7 days a week
• Go to bed at the same time each night
• Exercise every day - exercise improves sleep!
• Deal with your worries before bedtime
• Plan for the next day before bedtime
• Set a worry time earlier in the evening
• Keep a journal

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More healthy sleep habits

• Adjust the bedroom environment
• Sleep is better in a cool room, around 65 F.
• Darker is better
• If you get up during the night to use the
  bathroom, use minimum light
• Use a white noise machine, a fan, or ear plugs to
  drown out other sounds
• Make sure your bed and pillow are comfortable
• If you have a partner who snores, kicks, etc.,
  you may have to move to another bed (try white
  noise first) (try ear plugs)
• Change resident hall quiet hours

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Healthy Sleep Habits

• Boring activities reading the phone book,
• count, etc.
• TV/video games do not count as relaxing or
  boringthe flashing lights stimulate the brain.

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• Insomnia
• Sleep Restriction
• Reducing time in bed to match sleep obtained
• To increase sleep efficiency
• Adherence is problematic
• Probably efficacious treatment

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Sleep Restriction - best if done with a
professional

• Cut bedtime to the actual amount of time you
  spend asleep (not in bed), but no less than 4
  hours per night
• No additional sleep is allowed outside these
  hours
• Record on your daily sleep log the actual amount
  of sleep obtained

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Sleep Restriction (contd)

• Compute sleep efficiency (total time asleep
  divided by total time in bed)
• Based on average of 5 nights sleep efficiency,
  increase sleep time by 15 minutes if efficiency
  is gt85-90
• With elderly, increase sleep time if efficiency
  gt80 and allow 30 minute nap.

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Sleep Restriction

• If sleep efficiency falls to less than 80,
  decrease time in bed by 15 minutes
• Have 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

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• Insomnia
• Relaxation
• To deactivate arousal system
• Various types - muscular, imaging, hypnosis,
  etc.
• Well established treatment

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BEHAVIORAL TREATMENTS

• Plan a relaxation period before bed, develop a
  bedtime routine.
• Relaxation Therapy
• Progressive muscle relaxation best
• EMG Biofeedback best
• Meditation
• Imagery training
• Self-hypnosis
• Diaphragmatic breathing

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Relaxation training

• More effective than no treatment, but not as
  effective as sleep restriction
• More useful with younger compared with older
  adults
• Engage in any activities that you find relaxing
  shortly before bed or while in bed
• Can include listening to a relaxation tape,
  soothing music, muscle relaxation exercises, a
  pleasant image

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• Insomnia
• Paradoxical Intention
• Engage in the feared outcome (not sleeping)
• Break cycle of performance anxiety
• Large variance in response

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Paradoxical Intention Treatment

• Paradoxical intention treatment is based on the
  concept that performance anxiety helps prevent
  proper sleep.
• The treatment involves persuading the individual
  with insomnia to engage in the most feared
  behavior, which to that individual is "staying
  awake."
• As the patient stops trying to fall asleep, the
  performance anxiety of trying to fall asleep
  slowly disappears.
• Studies show this approach is more effective than
  control groups.

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• Insomnia
• Cognitive Restructuring
• Identify thought processes to reduce anxiety
• Includes self-talk, distraction, rationalization
• Helpful in altering dysfunctional sleep beliefs
• Postponing worry episodes
• Limited benefits if used alone, Not sufficient
  as a stand alone treatment

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Cognitive Restructuring

• Identify beliefs about sleep that are incorrect
• Challenge their truthfulness
• Substitute realistic thoughts

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False beliefs about insomnia

• Misconceptions about causes of insomnia
• Insomnia is a normal part of aging.
• Unrealistic expectations re sleep needs
• I must have 8 hours of sleep each night.
• Faulty beliefs about insomnia consequences
• Insomnia can make me sick or cause a mental
  breakdown.
• Misattributions of daytime impairments
• Ive had a bad day because of my insomnia.
• I cant have a normal day after a sleepless
  night.

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More common myths about insomnia

• Misconceptions about control and predictability
  of sleep
• I cant predict when Ill sleep well or badly.
• Myths about what behaviors lead to good sleep
• When I have trouble getting to sleep, I should
  stay in bed and try harder.

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EFFICACY OF CBTI FOR INSOMNIA
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EFFICACY OF CBT FOR INSOMNIA
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Benefits of CBTI

• Benefits are long-lasting, even after therapy is
  over
• Relatively free of medical risks
• No significant interactions with other medical
  treatments

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The Down Side of CBTI

• Monetary cost (repeated visits to a provider)
• Improvement may not occur for several weeks
• Requires time and motivation
• Daytime sleepiness during sleep restriction
• Lack of access to a trained therapist
• Lack of therapist expertise

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Combined Treatment

• CBTI can be used along with medications.
• For example, medications can provide rapid relief
  and CBTI can lead to long-lasting results.
• The use of medication prior to the initiation of
  behavioral therapy appears to be less effective.

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Treatment of Insomnia

• Pharmacologic
• Sleeping Pills-Prescription
• Over the Counter

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Pharmacologic Treatment of Insomnia

• Historic trials
• Fermented beverages
• Plant preparations
• Laudanum (opium/alcohol)
• Chloral hydrate (Mickey Finn)
• Barbiturates

• Current
• Antihistamines
• Benzodiazepine hypnotics
• Nonbenzodiazepine hypnotics
• Selective melatonin receptor agonist
• Investigational compounds

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MOST COMMONLY USED DRUGS FOR INSOMNIA

• Trazodone
• Zolpidem
• Amitriptyline
• Mirtazapine
• Temazepam
• Quetiapine
• Zaleplon
• Clonazepam

• Hydroxyzine
• Alprazolam
• Lorazepam
• Olanzapine
• Flurazepam
• Doxepin
• Cyclobenzaprine
• Diphenhydramine

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Treatment of Insomnia

• 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
• Best if started with CBTI

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Sleeping Pills

• Most common treatment approach
• Drowsiness common the next day
• NOT meant for chronic insomnia
• Effective for short-term (a couple weeks)
  insomnia only
• Tolerance and dependency may develop
• Withdrawal, rebound, relapse may occur
• But commonly used, despite the above
• 5-10 of adults have used a benzodiazepine in
  past year as a sleep aid
• 10-20 of those over age 65 use sleeping pills

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Drug Treatment

• Benzodiazepines-Approved by FDA
• Non-benzodiazepine hypnotics-Approved by FDA
• Melatonin receptor agonists-Approved by FDA
• Antidepressants
• Antipsychotics
• Antihistamines

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Benzodiapines

• Many end in pam or lam
• clonazepam (Klonopin)
• lorazepam (Ativan)
• diazepam (Valium)
• alprazolam (Xanax)
• temazepam (Restoril)
• triazolam (Halcion)

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BZRA HYPNOTICS IN THE US
DRUG BRAND HALF-LIFE (hrs) DOSE (mg)
Estazolam ProSom 8-24 1,2
Flurazepam Dalmane 48-120 15,30
Quazepam Doral 48-120 7.5,15
Temazepam Restoril 8-20 7.5,15,22.5,30
Triazolam Halcion 2-4 0.125,0.25
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BZRA PRESCRIBING GUIDELINES

• Bedtime dosing
• Avoid hazardous activities after dose
• Allow sufficient time in bed
• Dose adjustments
• Elderly and debilitated patients
• Hepatic impairment
• Nightly vs. as needed dosing
• Middle of the night dosing?
• Taper dose on discontinuation?
• Do not use in pregnant patients

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Benefits of Benzodiazepines

• Enhance sleep
• Decrease anxiety
• Muscle relaxant

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BZRA DISCONTINUATION EFFECTS

• Rebound insomnia sleep worsened relative to
  baseline for 1-2 days
• Recrudescence return of original insomnia
  symptoms
• Withdrawal new cluster of symptoms not present
  prior to treatment

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BZRA ADVERSE EFFECTS

• Residual effects
• Dizziness
• Headache
• Blurred vision
• Nausea/diarrhea
• Fatigue
• Anterograde amnesia
• Sonambulism/complex sleep behavior

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Side Effects of Benzodiazepines

• Daytime sedation
• Decreased reaction time
• Unsteadiness of gaitcan lead to falls, ataxia
• Cognitive impairment memory problems
• Risk of tolerance
• Risk of withdrawal (and rebound insomnia)
• Risk of abuse (do not use them in patients with a
  history of substance abuse)

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Non-BZRA HYPNOTICS IN THE US
DRUG BRAND HALF-LIFE (hrs) DOSE (mg)
Zolpidem Ambien 1.5-2.4 5,10
Zolpidem ER Ambien CR 2.8-2.9 6.25,12.5
Zaleplon Sonata 1 5,10
Eszopiclone Lunesta 5-7 1,2,3
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Benefits of Non-benzodiazepines Hypnotics

• Bind to sub-types of GABA receptors that
  specifically modulate sleep and therefore are
  thought to have less unwanted side effects
• Tolerance and abuse have not been shown to be a
  major problem in the general population
• In general have shorter duration of action than
  most benzodiazepines and therefore are less
  likely to cause next day sedation

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Side Effects of Non-benzodiazepines Hypnotics

• Drowsiness
• Dizziness
• Unsteadiness of gait
• Rebound insomnia
• Memory impairment

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FDA Indications

• Sleep onset only zolpidem (Ambien) and zaleplon
  (Sonata)
• Sleep onset and sleep maintenance zolpidem ER
  (Ambien ER) and eszopiclone (Lunesta)
• Eszopiclone (Lunesta) does not have a FDA
  restriction on duration of usage

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FDA Indications

• Benzodiazepine receptor agonists
• Benzodiazepine hypnotics
• Temazepam (Restoril) (generic available)
• Flurazepam (Dalmane) (generic available)
• Nonbenzodiazepine hypnotics
• Zolpidem (Ambien) (generic available)
• Zaleplon (Sonata) (generic available)
• Eszopiclone (Lunesta) ( no generic available)
• Selective melatonin receptor agonist
• Ramelteon (Rozerem) (no generic available)

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Ramelteon

• Brand name is Rozerem
• Selective agonist at MT1 and MT2 melatonin
  receptors
• FDA approved for sleep-onset insomnia
• Only medication FDA approved for insomnia that is
  not a controlled substance because it does not
  seem to lead to abuse or withdrawal
• Associated with headache, dizziness, drowsiness,
  fatigue and nausea
• Avoid with hepatic impairment and in pregnant
  women

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Ramelteon

• FDA approved for sleep onset insomnia
• No limitation on duration of use
• Non-sedating
• Single dose 8 mg
• Take about 30 minutes prior to bedtime
• Half-life 1-2.6 hrs
• No generic yet

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First Generation Antihistamine

• Postsynaptic histaminic and muscarinic blockade
• Diphenhydramine
• Regulated by the FDA
• Half-life 8 hrs
• Rapid tolerance to sedating effects
• Pill strengths (mg) 25, 37.5, 50

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First Generation Antihistamine

• Potential adverse effects
• Residual effects
• Delirium
• Dry mouth
• Constipation
• Blurred vision
• Urinary retention
• Narrow angle glaucoma exacerbation
• Paradoxical reaction

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Anti-depressants

• Commonly used for insomnia but are not FDA
  approved
• Trazodone
• Doxepin (Sinequan)
• Amitriptyline
• Mirtazapine (Remeron)

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Trazadone

• Used at much lower doses for insomnia than
  depression
• The most commonly prescribed agent for treating
  insomnia across all classes of medications
• No good research to support its use
• Major side effects sedation, dizziness, dry
  mouth, orthostatic hypotension, priapism (rare)

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The Tricyclic Antidepressants

• amitriptyline (Elavil)
• doxepin (Sinequan)
• Side effects dry mouth, urinary retention,
  dizziness, daytime sedation, suppression of REM
  sleep, QT prolongation
• Used at much lower doses for insomnia than
  depression

120
Mirtazapine

• Brand name Remeron
• Associated with weight gain, increased appetite,
  daytime sedation and dizziness

121
Antipsychotics

• Called the atypical antipsychotics
• Block dopamine from binding to receptors in the
  brain
• Only use is for treating comorbid insomnia in
  patients with primary indication for their use
• Examples
• risperidone (Risperdal)
• olanzapine (Zyprexa)
• quetiapine (Seroquel)
• ziprasidone (Geodon)

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Anticonvulsants

• Low doses have some sedating and sleep promoting
  effects
• The data is sparse

123
Dietary Supplements

• Not FDA regulated
• Valerian
• Kava-Kava
• Melatonin
• Passion flower
• Skullcap
• Lavender
• Hops

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Dietary/Herbal Sleep Preparations(pea-shooters
in the armamentarium)

• Mostly L-Tryptophan, Valerian, Kava-kava
• L-Tryptophan precursor of Serotonin, a substrate
  for Melatonin in milk (doesnt need to be
  warmed) turkey FDA has limited availability
  after gt 1,500 cases of Eosinophilia Myalgia
  Syndrome with at least 37 deaths in 1989

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Dietary/Herbal (continued)

• Valerian (derivative of Valeriana officinalis
  plant) mechanism may be via inhibiting GABA
  reuptake or inhibiting postsynaptic potentials
  through activation of adenosine receptors in
  cortical neurons in one study, little
  difference vs. Benadryl - inhibitor of CYP3A4
  withdrawal when extensive use, similar to that
  seen with BZDs risk of hepatotoxicity
  delirium
• 
  Sleep, 2005, 28 1465-1471

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Dietary/Herbal (continued)

• Kava-kava from root of Piper methysticum plant
  endogenous to Western Pacific, and used as
  hypnotic anxiolytic banned in many countries
  due to reports of serious hepatoxicity
• ______________________
• Others Melatonin (OTC), Chamomilla (Sleepy-Time
  Tea), Passiflora

127
Do Not Mix Medications

• Heath Ledger had insomnia and passed away from an
  accidental overdose of the following medications
• oxycodone
• hydrocodone
• diazepam
• temazepam
• alprazolam
• doxylamine

128
Other Treatments of Insomnia

• Acupuncture

129
Cultural Issues of Insomnia

• How long to sleep at night
• How long to nap
• Is insomnia to due too much work, physical
  ailments, etc.
• Is insomnia a disease, a complaint, a disorder, a
  symptom, a finding

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Brief Behavioral Treatment Plan for Insomnia

• Initial Visit
• (1) Screen positive for possible insomnia.
• (2) Assign sleep log and teach how to complete it
  on daily basis for 2 weeks.
• (3) Teach how to calculate a daily sleep
  efficiency score.
• Sleep efficiency is calculated by taking the
  ratio of actual time spent asleep to time spent
  in bed (expressed as a percentage, with higher
  numbers indicating better sleep efficiency).

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Brief Behavioral Treatment Plan for Insomnia

• First Treatment Session (2 weeks later)
• (1) Review of sleep log, including sleep
  efficiency score, especially to see the amount of
  time napping.
• (2) Discussion of bedtime habits (e.g.,
  television watching, reading, worrying, etc.).
• (3) Brief sleep education consisting of
  individual differences in sleep needs, the
  effects of aging on sleep, and the influence of
  sleep drive and circadian rhythms on sleep.
• (4) Teach stimulus control techniques including
  (a) eliminating nonsleep-related activities from
  bed and bedroom, (b) following a consistent
  sleep-wake schedule, and (c) avoiding daytime
  napping.

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Brief Behavioral Treatment Plan for Insomnia

• Second Treatment Session (4 weeks after initial
  visit)
• (1) Review of first treatment session
  instructions.
• (2) Problem-solving of any potential treatment
  adherence problems.
• (3) Possible modification of patient's sleep
  strategy and instructions to encourage future
  independent trouble-shooting.

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Brief Behavioral Treatment Plan for Insomnia

• Edinger and Sampson conducted a randomized trial
  of primary care patients with insomnia.
• Their abbreviated behavioral therapy of two
  25-minute sessions was compared with a control
  group receiving 2 sessions of standard sleep
  hygiene instructions.
• Those in the treatment group had greater
  improvements in their sleep efficiency and
  reductions in their time awake after sleep onset
  than the control group.
• This treatment can be successfully done by
  nonmental health professionals, providers,
  working in primary care settings.

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Take Home Points

• In practice parameters for nonpharmacologic
  treatments for chronic insomnia, the American
  Academy of Sleep Medicine recommends stimulus
  control as the approach with the best scientific
  evidence for effectiveness.
• Progressive muscle relaxation, paradoxical
  intention, and biofeedback are 3 treatments that
  have the next best scientific evidence for
  effectiveness, while sleep restriction and
  multicomponent cognitive behavioral therapy are
  recommended as options.
• Focusing on sleep hygiene and single component
  cognitive therapy may also be effective, but
  these approaches do not currently have sufficient
  scientific evidence to recommend them as
  evidence-based treatment. This is due to the
  insufficient number of clinical trials studying
  the effectiveness of these treatments alone,
  without their being part of any combined
  treatment regimen.

137
Take Home Points

• In the immediate short term (i.e., first week),
  medications can produce improvement at a much
  greater rate than nonmedication treatments.
• In the intermediate term (i.e., 3-8 weeks), a
  meta-analysis indicates that behavioral treatment
  for insomnia is just as effective as medication
  treatment.

138
Take Home Points

• There is the possibility that this effectiveness
  of behavioral treatment is because it is more
  intensive than medication treatment in that there
  is a greater duration of contact with the
  healthcare professional.
• Over the long term (i.e., 6-24 months), patients
  receiving nonpharmacologic therapies enjoy long
  lasting relief while many of those treated with
  medication return to their baseline insomnia
  levels.
• In summary, behavioral therapy is best for
  chronic insomnia and helpful for all types.

139
Take Home Points

• Insomnia is defined by having daytime symptoms.
• There are two pathways for treating insomnia
  medications and CBTI. They can be used at the
  same time.
• All treatments have their pluses and their
  minuses. Providers look at the patients
  impairment and weigh that against the risk of
  treatment.

140
Take Home Points

• Patients with insomnia typically feel fatigued
  during the day, but are unable to fall asleep if
  given a chance to lie down to take a nap.
• Patients with poor nocturnal sleep due to other
  sleep disorders readily fall asleep during the
  day.

141
Take Home Points

• Many of the most common drugs for insomnia are
  not FDA approved for that purpose.
• No drug for insomnia is completely safe or free
  of the risk of side effects.
• Be sure that your patients informs you of all
  medications they are taking, including
  over-the-counter and herbal ones.

142
Take Home Points

• Multidimensional Cognitive Behavioral Therapy
  works better than both placebo and
  pharmacotherapy (medicines) in short and long
  term cases
• Interventions for sleep practices may need to be
  culture specific

143
Recommendations

• Acknowledge that students sleep habits are
  significant concerns
• Educational programs have been shown to be more
  effective the pharmacologic and CBTI long term
• Examine course schedules, offer sections later in
  the day
• Examine how campus and community environments
  contribute to sleep difficulties

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Recommendations

• Do activities, schedules, sports, work routines
  contribute to sleep difficulties
• Review life style issues sleep, etc at all
  clinic visits