Ruth Benca, MD PhD Wisconsin Sleep Insomnia and Primary Care
Diagnosis requires one or more of the following:
difficulty initiating sleep
difficulty maintaining sleep
waking up too early, or
sleep that is chronically nonrestorative or poor in quality
Sleep difficulty occurs despite adequate opportunity and circumstances for sleep.
Insomnia is not sleep deprivation, but the two may coexist.
Insomnia defined American Academy of Sleep Medicine. International classification of sleep disorders, 2nd ed.: Diagnostic and coding manual. Westchester, Illinois: American Academy of Sleep Medicine, 2005.
At least one daytime impairment related to the nighttime sleep difficulty must be present:
Attention, concentration, or memory impairment
Social/vocational dysfunction or poor school performance
Proneness for errors/accident at work or while driving
Tension headaches, and/or GI symptoms in response to sleep loss
Concerns or worries about sleep
Insomnia must be associated with daytime impairment American Academy of Sleep Medicine. International classification of sleep disorders, 2nd ed.: Diagnostic and coding manual. Westchester, Illinois: American Academy of Sleep Medicine, 2005.
Impacts quality of life and worsens clinical outcomes 1,2
Predisposes patients to recurrence 3
May continue despite treatment of the primary condition 4
“ Comorbid insomnia” more appropriate than “secondary insomnia,” because limited understanding of mechanistic pathways in chronic insomnia precludes drawing firm conclusions about the nature of these associations or direction of causality. Considering insomnia to be “secondary” may also result in undertreatment. 5
1 Roth T, Ancoli-Israel S. Sleep . 1999;22:S354-S358. 2 Katz DA, McHorney CA. J Fam Pract . 2002;51:229-235. 3 Chang PP, et al. Am J Epidemiol . 1997;146:105-114. 4 Ohayon MM, Roth T. Psychiatr Res . 2003;37:9-15. 5 National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults, June 13-15, 2005. National Institutes of Health. Sleep . 2005 Sep 1;28(9):1049-1057.
Epidemiology of insomnia
General population: 10-15%
Clinical Practice: > 50%
The prevalence and treatment of primary insomnia have been the most studied (less than 20% of cases) 1,2
Comorbid insomnia accounts for > 80% of cases
1 Simon GE,Vonkorff M. Am J Psychiatry . 1997;154:1417-1423. 2 Hajak G. Sleep . 2000; 23:S54-S63.
At-risk populations for insomnia
Comorbid medical illness (especially respiratory, chronic pain, neurological disorders)
Increased prevalence of medical disorders in those with insomnia Taylor DJ., et al. Sleep. 2007;30(2):213-218 . p values are for Odds Ratios adjusted for depression, anxiety, and sleep disorder symptoms. From a community-based population of 772 men and women, aged 20 to 98 years old. Heart Disease Cancer HTN Neuro-logic Breath-ing Urinary Diabetes Chronic Pain GI Any medical problem % N=137 N=401 p <.05 p <.05 p <.01 p <.01 p <.001 p <.001 p <.001 p <.001
Increased prevalence of insomnia in those with medical disorders Prevalence, % Survey Of Adults (N=2101) Living In Tucson, Arizona, Assessed Via Self-administered Questionnaires * * ** * * Klink ME et al. Arch Intern Med . 1992;152:1634-1637. * P ≤ .001, ** P ≤ .005 vs. no health problem ASVD, arteriosclerotic vascular disease; OAD, obstructive airway disease.
Insomnia prevalence increases with greater medical comorbidity Foley D, et al. J Psychosom Res . 2004;56:497-502. Self-reported questionnaire data from 1506 community-dwelling subjects aged 55 to 84 years 80 Number of Medical Conditions 0 10 20 30 40 50 60 70 Percent of Respondents Reporting any Insomnia 0 1 2 or 3 4
Psychiatric disorder is the most common condition comorbid with insomnia Adjustment disorder (2%) Anxiety disorder (24%) Bipolar disorder (2%) Depressive disorder (8%) Psychiatric Disorders (36%) Other DSM-IV Distribution of Insomnia(64%) No DSM-IV diagnosis (24%) Other sleep disorders (5%) Insomnia due to a general medical condition (7%) Substance-induced insomnia (2%) Insomnia related to another mental disorder (10%) Primary insomnia (16%) Ohayon MM. Sleep Med Rev . 2002;6:97-111. N=20,536. European meta-analysis
Relative risk for psychiatric disorders associated with insomnia 1 Breslau N, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry . 1996;39:411-418. 2 Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA . 1989;262(11):1479-1484. 1 Breslau, 1996. N=1007 2 Ford and Kamerow, 1989. N=811 1 1 1 2 2 1,2 1,2 1,2 1,2
Timing of insomnia related to onset of psychiatric illness Ohayon MM , Roth T. J Psychosom Res . 2003;37:9-15. N=14,915
Insomnia is a risk factor for later-life depression * Number of men included at each time point. Chang P et al. Am J Epidemiol . 1997;146:105-114. Insomnia* Yes 137 135 133 127 117 106 99 27 9 No 887 877 859 838 799 740 616 382 216 Cumulative Incidence (%) Yes No Total Cases 137 23 887 76 Insomnia P =.0005 Follow-up Time (Years) 0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Objective sleep abnormalities are seen in psychiatric patients Comparison of sleep EEG in groups of patients with psychiatric disorders or insomnia to age-matched normal controls. Benca RM et al. Arch Gen Psych . 1992;49:651-668 TST SE SL SWS REM L Mood Alcoholism Anxiety Disorders Schizophrenia Insomnia
Bidirectional relationship between psychiatric disorders and insomnia ACTH, adrenocorticotropic hormone TST, total sleep time SOL, sleep onset latency SWS, slow wave sleep
Sleep and menopause
Peri- and postmenopausal women have more sleep complaints 1
41% of early perimenopausal women report sleep difficulties 2
Frequent awakenings suggest insomnia is secondary to vasomotor symptoms 3
However, waking episodes may occur in absence of hot flashes 4
1 Young T, et al. Sleep . 2003;26:667-672. 2 Gold E, et al. Am J Epidemiol . 2000;152:463-473. 3 Woodward S, Freedman RR. Sleep .1994;17:497-501. 4 Polo-Kantola P, et al. Obstet Gynecol . 1999;94:219-224.
Complaints of sleep problems with age Age Group, y 50 40 30 20 10 0 Percent 10-19 20-29 30-39 40-49 50-59 60-69 70+ “ Trouble With Sleeping” Assessed in a comprehensive survey of 1645 individuals in Alachua County, Florida Karacan I et al. Soc Sci Med . 1976;10:239-244.
Prevalence of insomnia by age group % Age Group, years Large-scale community survey of non-institutionalized American adults, aged 18 to 79 years Mellenger GD, et al. Arch Gen Psychiatry . 1985;42:225-232.
Patients with pain report poor sleep
287 subjects reporting to pain clinic
Mean age, 46.7 years; half with back pain
89% reported at least 1 problem with sleep
Significant correlations between sleep and
McCracken LM, Iverson GL. Pain Res Manag . 2002;7:75-79.
Insomnia comorbid with pain N=18,980; p <.001. Based on survey data. *Pain categories included limb pain, backaches, joint pain, GI pain, and headaches. Ohayon MM. J Psychiatr Res . 2005 Mar;39(2):151-159. Control Any pain* %
Bidirectional relationship between pain and insomnia DIS, difficulty initiating sleep DMS, difficulty maintaining sleep
Sleep and cancer
30% to 75% of newly diagnosed or recently treated cancer patients complain of insomnia (double that of the general population)
Sleep complaints in cancer patients consist of
difficulty falling asleep
difficulty staying asleep
frequent and prolonged nighttime awakenings
Complaints occur before, during and after treatment
Fiorentino L, Ancoli-Israel, S. Sleep dysfunction in patients with cancer. Curr Treat Opt Neurol. 2007;9:337–346.
Bidirectional relationship between insomnia and cancer SDB, sleep-disordered breathing Fiorentino L, Ancoli-Israel, S. Sleep dysfunction in patients with cancer. Curr Treat Opt Neurol. 2007;9:337–346.
Insomnia and OSA or CSA
Studies have shown that 39% to 55% of patients with OSA have comorbid insomnia. Associated factors include:
OSA patients with comorbid insomnia have
More severe sleep apnea
Increased depression, anxiety and stress
Krell SB, Kapur VK. Sleep Breathing. 2005;9:104-10. Smith S, et al. Sleep Med. 2004;5:449-456. AHI, apnea hypopnea index. CSA, central sleep apnea. DI, desaturation index. OSA, obstructive sleep apnea.
restless leg symptoms
lower AHI, lower DI
Insomnia and OSA or CSA
< 1% of 1,000 patients with OSA surveyed had been diagnosed with insomnia
Mood problems were not formally addressed
In a small study of patients with CSA (n=14):
36% had sleep onset insomnia
79% had maintenance insomnia
This rate was significantly higher than in patients with OSA ( P =.016)
Morganthaler TI,et al. Sleep . 2006;29:1203-1209. Smith S, et al. Sleep Med. 2004;5:449-456.
Insomnia and COPD
>50% of patients with COPD have insomnia
25% complain of excessive daytime sleepiness
Medications for COPD contribute to insomnia
Inhaled or PO; anticholinergics, corticosteroids, beta-2-agonists, theophylline; bupropion used for smoking cessation
Sleep deprivation may attenuate ventilatory response to hypercapnia in patients with COPD, leading to further desaturation and sleep disruption
George CFP. Sleep . 2000;23:S31-S35. White DP, et al. Am Rev Respir Dis. 1983;128:984-986.
Insomnia and COPD
Insomnia linked with comorbidities of COPD
Eg, depression, smoking, orthopnea, and nocturnal hypoxemia
Suggests multiple factors in pathogenesis of insomnia in COPD
Insomnia can impair pulmonary function
Spirometric decline is observed after one night of sleep deprivation
Despite importance of treating the underlying COPD, this may not lead to improvement of insomnia in clinical practice
Cormick W, et al. Thorax . 1986;41:846-854. Kutty K. Curr Opin Pulm Med. 2004;10:104-112. Maggia S, et al. J Am Geriatric Soc. 1998;46:161-168. Phillips BA, et al. Chest . 1987;91:29-32. Wetter DW, et al. Prev Med. 1994;23:328-334.
Insomnia may be a predictor of hypertension N=9237 male Japanese workers assessed for difficulty initiating and/or maintaining sleep and followed up for 4 years or until the development of HTN (initiation of anti-HTN therapy or a SBP of ≥140 mmHg or a DBP of ≥140 mmHg). Results adjusted for BMI, tobacco and alcohol use and job stress. Suka M, et al. J Occup Health . 2003;45:344-350. HTN Incidence (%) n=4602 n=192 n=4157 n=286 95% CI: 1.42-2.70 95% CI: 1.45-2.45
Short sleep duration and hypertension: NHANES I and the Sleep Heart Health Study Gangwisch et al. Hypertension. 2006;47:833-839. Gottlieb DJ, et al. Sleep . 2006;29(8):1009-1014. ≤ 5h 6h 7-8h ≥ 9h ≤ 6h 6-7h 7-8h 8-9h ≥ 9h (1.0; referent) (1.0; referent) Hazard Ratios. N=4180. Subjects 32-59y. Sleep duration and increased risk of HTN, adjusted for multiple confounders including physical activity, alcohol/salt consumption, smoking, age, overweight/obesity, and diabetes. Odds Ratios . N=5910. Subjects 40-100y. Sleep duration and increased risk of HTN adjusted for age, sex, race, apnea-hypopnea index and BMI.
Relationships between sleep disorders* and obesity * Insomnia or sleep deprivation. 1 Bjorvatn B, et al. J Sleep Res . 2007;16(1):66-76. 2 Flint J, et al. J Pediatr . 2007;150(4):364-369. 3 Chaput JP, et al. Obesity (Silver Spring) . 2007;15(1):253-261. 4 Gottlieb et al. Arch Intern Med . 2005;165:863-868. Factors associated with reduced sleep time* may contribute to obesity
Management of insomnia
Treat any underlying cause(s)/comorbid conditions
Promote good sleep habits (improve sleep hygiene)
Consider cognitive behavior therapy
Consider medications to improve sleep
Kupfer DJ and Reynolds CF III. N Engl J Med . 1997;336:341-346.
Practicing good sleep hygiene
“ watching the clock”
use of stimulants, eg, caffeine, nicotine, particularly near bedtime 1,3
heavy meals or drinking alcohol within 3 hours of bed 1
exposure to bright light during the night 1,3
Enhance sleep environment: dark, quiet, cool temperature 1,3
Increase exposure to bright light during the day 2
Practice relaxing routine 1-3
Reduce time in bed; regular sleep/wake cycle 1-3
Time regular exercise for the morning and/or afternoon 1,3
1 NHLBI Working Group on Insomnia. 1998. NIH Publication . 98-4088. 2 Kupfer DJ, Reynolds CF. N Engl J Med . 1997;336:341-346. 3 Lippmann S et al. South Med J . 2001;94:866-873.
Behavioral techniques Technique Aim Stimulus control therapy Imprint bed and bedroom as sleep stimulus Sleep restriction Restrict actual time spent in bed to enhance sleep depth & consolidation Cognitive therapy Address dysfunctional beliefs and attitudes about sleep Relaxation training Decrease arousal and anxiety Circadian rhythm entrainment Reinforce or reset biological rhythm using light and/or chronotherapy Cognitive behavior therapy Combination of behavioral and cognitive approaches listed above
Patients with psychoactive substance use disorder history
Patients with insomnia related to depression, anxiety
Treatment failures with BzRA
Suspected sleep apnea
Primary insomnia (second-line agents)
Not FDA-approved for use as hypnotics
Antidepressant drug effects on sleep Sleep continuity Slow wave sleep REM sleep Other Tricyclic To To To PLMs Apnea SSRI To To To Eye movements in NREM PLM apnea Trazodone, Nefazodone To To Trazodone more sedating Bupropion To No increase in PLM Mirtazapine Low doses sedating
When to refer an insomnia patient to Sleep Clinic:
Medical and psychiatric comorbidities have been assessed and are adequately treated
Patient has been instructed in sleep hygiene
Patient has failed trials of behavioral and/or pharmacological therapy
Other common sleep disorders treated by sleep specialists:
Restless legs/periodic limb movement disorder
Circadian rhythm disorders
*Typically require sleep laboratory testing as well as clinical evaluation for diagnosis
High density-EEG / TMS studies in health and disease pioneered by Giulio Tononi, MD, PhD High density EEG (256 electrodes) recorded across entire night, TMS in wakefulness and sleep
Why high-density EEG in sleep?
Can now be done routinely; noninvasive and relatively inexpensive
What could be done with standard PSG has largely been done (NIH roadmap discourages it)
Sleep apnea PSG likely to migrate to home-monitoring
Spatial resolution is comparable to PET; temporal resolution is ideal
Sleep is a window on spontaneous brain function, unconfounded by attention, motivation, etc.