OPTIONS FOR A BAD NIGHT'S SLEEP
From Sleep Disorders 2008, sponsored by the Loma Linda University School of Medicine, in conjunction with World Class
CME and the National Sleep Foundation
Educational Objectives
| The goal of this program is to improve the management of insomnia. After hearing and assimilating this program, the clinician
will be better able to:
|
 | 1. Discuss the pathways that contribute to the development of insomnia.
|
| 2. Review the information necessary for obtaining a clinical history of insomnia.
|
| 3. Recommend therapy for circadian rhythm disorders.
|
| 4. Describe characteristics of pharmacologic therapy options for insomnia.
|
| 5. Recognize when nonpharmacologic therapy is appropriate for insomnia.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health
care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Pigeon
has received research support from CherryPharm and Cephalon, and is a sponsored speaker for Pri-Med Conferences. Dr.
Simon and the planning committee reported nothing to disclose.
Acknowledgments
Drs. Pigeon and Simon were recorded at Sleep Disorders 2008, held March 17-19, 2008, in Orlando, FL, and sponsored
by Loma Linda University School of Medicine, in conjunction with World Class CME and the National Sleep
Foundation. The Audio-Digest Foundation thanks the speakers and Loma Linda University School of Medicine for
their cooperation in the production of this program.
| INSOMNIA: PATHOPHYSIOLOGY AND DIAGNOSIS —Wilfred R. Pigeon, PhD, Senior Instructor, Department of Psychiatry,
and Assistant Director, Sleep Research Laboratory, University of Rochester Medical School, Rochester, NY
|
| Epidemiology: high prevalence rate; ≈50% of individuals presenting to any clinical practice (across specialties) complain
of insomnia; definitions—inability to sleep for 3 successive nights for 2- to 4-wk period, precipitated by stressful
life event (reported by ≈30% of individuals at any given time); chronic condition that lasts for 1, 3, or 6 mo (experienced
by 8%-10% of population in Western Europe, North America, and parts of Asia); prevalence of insomnia increases with
age; by 60s and 70s, prevalence rate 25% to 30%, then levels off; women tend to complain of insomnia after second,
third, or fourth child; rates increase during menopause for majority of women; in their 20s, most individual’s complaints
involve sleep initiation difficulties (conversely, in older adults, complaints involve sleep maintenance difficulties)
|
| Pathophysiology: several putative pathways (physiologic, cognitive, behavioral, circadian, and homeostatic) may contribute
to insomnia; from physiologic perspective—individuals with insomnia exhibit increased metabolic rate; when
compared to healthy normal sleepers, those in insomnia group had higher 24-hr cortisol concentrations; before sleep onset
and during first few hours of sleep, cortisol levels remain high in those with insomnia; when monitored with electroencephalography
(EEG), patients with insomnia shown to have high-frequency activity during night, compared to good
sleepers (ie, controls); β activity in stage 2 sleep not seen in good sleeper (conversely, β, γ, and other fast-frequency EEG
spectrum seen in patients with insomnia); from cognitive perspective—patients with insomnia tend to worry, ruminate,
have intrusive thoughts, selectively attend to stimuli, have sleep-related intention and effort, and sleep-related safety behaviors;
behavioral factors that lead to or cause insomnia—bedroom and bedtime paired with sleep (and sexual activity)
in individual with good stimulus control; in individual with insomnia, stimulus dyscontrol observed (ie, bedroom and
bedtime not only paired with sleep and sexual activity, but also with eating, reading, watching television, working, worrying,
and cleaning); homeostatic and circadian factors—over 24-hr day, longer the person awake, higher the sleep drive;
as person falls asleep, sleep drive dissipates; if combined with notion of circadian rhythm (individuals designed to sleep
during night and be awake during daylight), wakefulness (in circadian sense) trumps sleepiness (in homeostatic sense);
individuals with insomnia often have mismatch between circadian and homeostatic drives; 7 studies using multiple sleep
latency test found that people with insomnia not sleepier than normal controls (indication that sleep drive mechanism not
working properly); slow-wave sleep (stages 3 and 4) marker for properly functioning sleep homeostasis; studies show
people with insomnia have less slow-wave sleep, despite same amount of sleep time
|
| Conceptual model of insomnia: 3P model—includes predisposing factors (eg, being woman), precipitating factors
(life events that cause insomnia), and perpetuating factors (eg, ineffective hypnotic strategies, over-the-counter medications
and alcohol, counter-fatigue measures, extending sleep opportunity, various rituals and idiosyncratic strategies)
|
| Diagnosis and evaluation: no diagnostic criteria for time awake, time asleep, and frequency; instead, criteria include
difficulty initiating or maintaining sleep and/or unrefreshing sleep experienced as disturbing to patient, and daytime
consequences (eg, fatigue, malaise, sleepiness); when assessing for insomnia, must have sleep complaint; if sleep complaint
present, must have adequate sleep opportunity (if so, make sure daytime deficit present); if all factors present,
criteria for insomnia met; insomnia possibly initiation insomnia, middle-of-night awakenings lasting 5 or 10 min, and/
or early morning awakening; sleep diary—best way to evaluate for insomnia; maintained by patient; typically kept for
1 wk; includes time patient goes to bed, time lights off, length of time to fall asleep, number of times patient awakens,
length of time patient awake in middle of night, and time patient arises; total sleep time and weekly average calculated;
clinical history—includes nature of complaint, time of onset, precipitants, course, frequency, daytime consequences,
and associated behaviors; bed partner helpful in identifying some factors; cognitions related to sleep; clinical
assessment—should include medical and neurologic examinations and psychiatric evaluation (high degree of comorbidity);
polysomnography (PSG) not indicated for routine evaluation of insomnia; indicated when comorbid sleep disorders
suspected
|
| Acute insomnia: usually self-limited, short in duration, and related to acute stressor; may become chronic if complicated
by perpetuating factors
|
| Chronic insomnia: idiopathic—develops in childhood; paradoxic—patient reports extended hours of awake time, with
large mismatch on PSG (subjective-objective mismatch); psychophysiologic—evidence of heightened arousal and
conditioning necessary; comorbid—wide spectrum of psychiatric disorders in which insomnia prevalent; especially
prevalent with mood disorders and depression, but also associated with generalized anxiety disorder, panic disorder,
and posttraumatic stress disorder, and less so in personality disorder and psychosis; presence of obstructive sleep apnea
(OSA) does not exclude presence of insomnia; substances possible precipitating factors
|
| MANAGEMENT OF INSOMNIA —Richard D. Simon Jr, MD, Assistant Clinical Professor of Medicine, University of
Washington School of Medicine, Seattle, and Medical Director, Kathryn Severyns Dement Sleep Disorders Center, St. Mary
Medical Center, Walla Walla, WA
|
| Biologic clock: desired goal to sleep when biologic clock not alerting us; unsuccessful if individual attempting to sleep
when biologic clock maximally alert; first step determining when biologic clock turned on and off; determining individual’s
circadian rhythm—ask patient “if given opportunity to sleep, when would you arise without having to use alarm
clock?” or ask when dip in alertness (ie, down time) noted; down time in afternoon due to interaction between biologic
clock (alerting) and homeostatic sleep drive; most people notice dip in alertness ≈8 hr after spontaneous wake time; another
approach is to determine when patient most alert (usually shortly after arising in morning and 2 to 3 hr before biologic
clock begins to turn off [second wind]); bright light able to alter biologic clock activity (but not by >2 hr daily); to
awaken earlier, person needs bright light in morning and minimal light in evening (or he or she can take melatonin in
evening); conversely, to awaken later, person should get bright light in evening and avoid morning light (or take melatonin
in morning)
|
| Circadian rhythm disorders: delayed sleep phase syndrome—patient unable to fall asleep at night (“night owl”);
clue to circadian rhythm abnormality is presence of insomnia during one-half of desired sleep schedule and hypersomnia
during other half; also, such patients usually have difficulty awakening in morning; advanced sleep phase syndrome—
early bedtime and early awakening in morning; early morning insomnia; treatment for delayed sleep phase syndrome—
establish spontaneous wake time; limit napping; provide bright light (blue light or full-spectrum; outdoors or artificial
light box) for ≈1 hr when person awakens spontaneously, then have patient awaken 30 to 60 min earlier every 2 days,
gradually pushing circadian phase until desired awakening time reached; also limit light at nighttime; melatonin or ramelteon
given 10 to 12 hr before desired wake time likely has similar effect; treatment for advanced sleep phase
syndrome—establish spontaneous wake time; limit napping; have patient get as much bright light as possible for ≈1 hr,
then let him or her go to bed; make sure bedroom absolutely dark in morning; delay bedtime by additional 30 to 60 min
every 2 to 3 days; for elderly, nighttime light very effective in improving sleep; melatonin or ramelteon given at early
morning awakening to delay sleep phase (melatonin at night advances sleep phase); possible for patient to have delayed
sleep phase syndrome and insomnia
|
| Homeostatic sleep mechanisms: need for sleep accumulates throughout day (ie, longer person awake, greater the accumulated
need to sleep); need for sleep met only by sleeping; also, the more one sleeps, the less need to sleep; napping
and insomnia—if person complains of insomnia and has to nap, subtract nap time from night sleep time
|
| Intrinsic sleep disorders: OSA—common; if patient placed on continuous positive airway pressure (CPAP), insomnia
usually resolves; if insomnia does not resolve, patient has comorbid insomnia and apnea; difficult to treat insomnia in
presence of other condition that fragments sleep; necessary to identify other condition (eg, OSA, restless legs syndrome,
circadian rhythm disorder) and treat; other considerations include environment and medical illnesses; several medications
fragment sleep; maximizing treatment does not mean adding more medications, but rather, using more appropriate medications
|
| Cognition: good sleepers enjoy sleeping, tolerate occasional bad night, and recognize that everyone sleeps poorly occasionally;
patients with insomnia tend to catastrophize, mislabel, overgeneralize, and feel that they need to stay in bed
longer
|
| Benzodiazepine receptor agonists: commonly used; no significant studies in insomnia absent depression or anxiety; side
effects, for most part, extensions of desired effect (sedation); increase transmission of γ-aminobutyric acid (GABA);
GABA-ergic receptors most common receptors in brain (medications not specific); associated with amnesia; duration
of action about twice half-life; possible rebound (insomnia worse than at beginning) lasting 2 to 3 days; speaker not
worried about addiction; abnormal nocturnal behaviors change arousal threshold; flurazepam—half-life 47 to 100 hr;
residual daytime dysfunction; eszopiclone—marginal; half-life 6 hr; some studies of parent compound (zopiclone)
show driving ability impaired 10 hr after ingesting; triazolam, zolpidem, and zaleplon safe, with short half-lives; no tolerance;
rebound insomnia low (<10% of patients); eszopiclone 10 mg shown effective long term; controversies—
speaker avoids problem of addiction by not escalating dose; if manufacturer’s recommended dose (Food and Drug Administration
[FDA]-approved dose) of hypnotic ineffective, higher dose not likely helpful; higher doses only increase
side effects (increasing duration of action); for chronic insomnia, speaker prescribes daily medication (compared to intermittent
dosing for acute insomnia); duration of therapy—longest double-blind placebo-controlled studies ≈6 mo;
contraindications—allergy; on-call responsibilities during duration of action; drug and alcohol use relative contraindication;
abnormal nocturnal behaviors while taking hypnotics; principles—use shortest-acting benzodiazepine receptor
agonist at lowest dose possible (especially in elderly); utilize sleep diary to document efficacy and if no improvement
seen, discontinue medication; speaker warns patient about drowsiness, amnesia, and possibility of rebound insomnia
|
| Antidepressants: speaker does not use for primary insomnia unless patient does not respond to hypnotic; studies show
paroxetine, trazodone, and doxepin effective, but associated with higher rates of side effects; one study suggests that
for comorbid depression and anxiety, not necessary to pick sedating antidepressant (treatment of depression important);
side effects significant
|
| Antihistamines: also not used by speaker for insomnia; half-life 10 to 12 hr; demonstrable effects in daytime; patient
should not drive if on sedating antihistamine
|
| Melatonin: fairly weak hypnotic; exception, patients with delayed sleep phase syndrome; effective if given at night to
“night owls” (actually treating circadian rhythm disorder); helpful in elderly with dementia and low melatonin profile;
if given at night to elderly, may worsen advanced sleep phase syndrome; helps and trains rhythms if given at night in
blind people; also helpful for those trying to sleep during periods of high biologic clock activity; vasoconstriction side
effect
|
| Ramelteon: selective melatonin receptor agonist; clinical data in humans limited to one study showing moderate efficacy;
effective in circadian reentrainment in rats
|
| Cognitive behavioral therapy (CBT): efficacy sustained over time; principles of improving sleep—maximize synchrony
between biologic clock and desired sleep-wake schedule, homeostatic sleep drive, and sleep-conducive factors
in social environment, and treat comorbid problems; awaken at approximately same time every day; bright light during
desired daytime hours; limit napping; avoid nicotine, caffeine, and ethanol; go to bed only when sleepy and awaken at
same time each day; exercise daily; keep bedroom comfortable
|
| Sleep restriction: most effective single CBT for insomnia; goal to increase sleep efficiency and break conditioned insomnia
(performance anxiety); requires motivated patient and motivated therapist; possibility of excessive daytime sleepiness;
establish hours in bed through sleep diary; limit time in bed to actual hours of sleep; as patient sleeps well, hours
of sleep increased every 3 days
|
| Stimulus control: involves minimizing alerting stimuli and maximizing sleep-producing stimuli; instruct patient to go to
bed only when sleepy; patient should get out of bed when unable to sleep, go to another room, perform boring activity,
and return to bed when sleepy (repeat as often as necessary); set alarm clock for same time each day; as soon as being
awake becomes bothersome, patient should get out of bed; use bedroom only for sleep and sex; curtail sleep-incompatible
activities; awaken same time every day, regardless of quality of sleep; avoid napping
|
| Relaxation therapy: type of relaxation not critical, but training critical
|
| Cognitive therapy: patient educated about sleep; change patient’s dysfunctional beliefs about sleep and heightened
arousal due to excessive preoccupation with sleep and next-day consequences; restructure dysfunctional sleep cognitions;
keep expectations realistic; do not give too much importance to sleep (eg, do not overdramatize one night of bad
sleep); have patient keep sleep diary and note inconsistencies; schedule 1-hr worry time before bed; CBT—
combination of therapies; tailored to individual; combined with gradual medication withdrawal, helps person discontinue
hypnotics; abbreviated CBT effective; group CBT effective when run by trained nurse practitioners; 4 sessions of
CBT better than 8 (at 6-mo follow-up)
|
| Treatment generalizations: hypnotics effective, but effects last only as long as drug used; effects of CBT durable (6
mo to 1 yr after completion of therapy); combining hypnotic with CBT results in rapid positive outcome; CBT (with or
without hypnotic) mainstay of treatment for chronic insomnia
|
Suggested Reading
Ancoll-Israel S: Sleep disorders in older adults. A primary care guide to assessing 4 common sleep problems in geriatric
patients. Geriatrics 59:37, 2004; Arendt J: Does melatonin improve sleep? Efficacy of melatonin. BMJ 332:550, 2006;
Basner RC: Shift-work sleep disorder--the glass is more than half empty. N Engl J Med 353:519, 2005; Buckley TM
et al: On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian
rhythm, exemplary sleep disorders. J Clin Endocrinol Metab 90:3106, 2005; Glass J et al: Sedative hypnotics in
older people with insomnia: meta-analysis of risks and benefits. BMJ 331:1169, 2005; Jacobs GD et al: Cognitive behavior
therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Intern Med
164:1888, 2004; Johnson MW et al: Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects.
Arch Gen Psychiatry 63:1149, 2006; Lu BS et al: Circadian rhythm sleep disorders. Chest 130:1915, 2006; Owens JA
et al: Improving sleep hygiene. Arch Intern Med 168:1229, 2008; Pearson NJ et al: Insomnia, trouble sleeping, and
complementary and alternative medicine: Analysis of the 2002 national health interview survey data. Arch Intern Med
166:1775, 2006; Revell VL et al: Advancing human circadian rhythms with afternoon melatonin and morning intermittent
bright light. J Clin Endocrinol Metab 91:54, 2006; Sateia MJ et al: Identification and management of insomnia.
Med Clin North Am 88:567, 2004; Sivertsen B et al: Cognitive behavioral therapy vs zopiclone for treatment of chronic
primary insomnia in older adults: a randomized controlled trial. JAMA 295:2851, 2006; Summers MO et al: Recent developments
in the classification, evaluation, and treatment of insomnia. Chest 130:276, 2006; Taylor JR et al: Pharmacologic
management of chronic insomnia. South Med J 99:1373, 2006; Waterhouse J et al: Jet lag: trends and coping
strategies. Lancet 369:1117, 2007; Whitworth JD et al: Clinical inquiries. Which nondrug alternatives can help with
insomnia? J Fam Pract 56:836, 2007; Yook K et al: Usefulness of mindfulness-based cognitive therapy for treating insomnia
in patients with anxiety disorders: a pilot study. J Nerv Ment Dis 196:501, 2008.
|
