Sleep

Insomnia

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Insomnia, Sleeplessness, Disorder of Initiating and Maintaining Sleep, DIMS, Sleep Initiation and Maintenance Disorder

  • See Also
  1. Insomnia in Children
  2. Insomnia Causes
  3. Medication Causes of Insomnia
  4. Sleep
  5. Circadian Rhythm Sleep Disorder
  6. Delayed Sleep Phase
  7. Dementia Related Sleep Problems
  • Epidemiology
  1. Most common sleep disorder in U.S. adults (affects up to 30%)
  • Causes
  1. See Insomnia Causes
  • Risk Factors
  1. Advancing age
    1. Incidence as high as 65% by age 65 years old
  2. Female gender
    1. Twice as common as in males
    2. More common with sex Hormone changes (third trimester pregnancy, Menopause)
  3. Living alone
  4. Comorbid mental health condition
    1. Anxiety Disorder
    2. Major Depression
    3. Post-Traumatic Stress Disorder (PTSD)
  5. Comorbid medical conditions
    1. Heart Failure
    2. Respiratory disease
    3. Neurologic disorders
    4. Chronic Pain
  6. Substance Abuse
    1. Alcoholism or Alcohol Withdrawal
    2. Opioid Abuse or Opioid Withdrawal
    3. Tobacco Abuse
  7. Life stressors
    1. Death in family or widowed
    2. Divorce or marital separation
    3. Unemployed or lower socioeconomic status
  1. Timing
    1. Duration: Transient Insomnia (<7 days), acute Insomnia (7-30 days) or chronic Insomnia (>30 days)
      1. Chronic Insomnia is best treated with Cognitive Behavioral Therapy
    2. Frequency: Occasional (weekly or less) or frequently to daily
      1. Occasional Insomnia may be best treated with as needed Sedative-Hypnotics
    3. Variation with weekend versus weekday
      1. Distinguish Delayed Sleep Phase syndrome from Insomnia
  2. Sleep Hygiene related behaviors
    1. Sleep environment (Sleep Hygiene related issues)
    2. Activities before sleep (e.g. Exercise, dinner)
    3. Sleep habits and history of problems (e.g. napping)
  3. Comorbid conditions
    1. See Organic Insomnia
    2. Substance use (Alcohol, Illicit Drugs)
    3. Limb Movement Disorders (e.g. Restless Leg Syndrome)
    4. Obstructive Sleep Apnea (e.g. loud snoring, Daytime Somnolence)
    5. Psychiatric Illness (40 to 50% of Insomnia patients)
      1. Major Depression
      2. Bipolar Disorder
      3. Excessive Worry
      4. Anxiety Disorder
    6. Substance use or abuse (e.g. Caffeine, Alcohol)
    7. Stressful life events (e.g. divorce, serious illness or death in family, unemployment)
    8. Chronic Pain
  1. Keep 2 week sleep log
  2. Times
    1. Bedtime, Awakening and total time in bed
    2. Sleep Onset Latency (time before falling asleep)
    3. Total time asleep
    4. Naps (number, time of day and duration)
    5. Number of nighttime awakenings
  3. Symptoms
    1. How well rested on awakening?
    2. How tired during the day (1=very tired, 5=wide awake)
    3. Irritability (1=none, 5=high)
  4. Predisposing Factors
    1. Number of drinks containing Alcohol
    2. Medications taken
    3. Emotional Stressors
  5. Adjunctive measures
    1. Actigraphy
  6. Resources
    1. Sleep Diary Chart (American Academy of Sleep Medicine)
      1. http://yoursleep.aasmnet.org/pdf/sleepdiary.pdf
    2. Sleep Diary Chart (Center for Deployment Psychology)
      1. http://deploymentpsych.org/system/files/member_resource/CDP%20Sleep%20Diary.pdf
  • Exam
  1. Thyroid examination
  2. Neurologic Examination
  3. Mini-Mental Status Exam (MMSE)
  • Diagnosis
  1. Complaints consistent with Insomnia (one or more)
    1. Difficulty initiating sleep (Sleep Latency) within 30 minutes
    2. Difficulty maintaining sleep (or poor quality sleep)
    3. Early awakening
  2. Daytime Impairment due to Insomnia (one or more)
    1. Impaired memory, concentration, attention
    2. Excessive Worry about sleep
    3. Daytime Somnolence, Fatigue, or malaise
    4. Depressed mood, irritability or poor motivation
    5. Accidents or errors while working or driving
    6. Poor work or school performance
    7. Tension Headaches or gastrointestinal upset
  3. Frequency
    1. At least 3 times weekly
  4. Duration
    1. Transient Insomnia: <7 days
    2. Acute Insomnia: <30 days
    3. Chronic Insomnia: 30 days or more
  5. Subtypes based on cause
    1. Primary Insomnia (no cause): <20% of chronic cases
      1. Difficult sleep despite adequate conditions and opportunity
      2. No other sleep disorder (e.g. Sleep Apnea)
    2. Comorbid Insomnia (Organic Insomnia)
      1. Insomnia secondary to other cause (medication, medical condition)
  • Management
  • Non-Pharmacologic
  1. Consider written sleep plan
  2. Lifestyle changes
    1. See Sleep Hygiene
    2. Regular Exercise (6 hours before bedtime)
      1. For age >65 years, Muscle endurance training and walking have best evidence
      2. Hasan (2022) Sleep Med Rev 65:101673 [PubMed]
      3. Xie (2021) Front Psychiatry 12:664499 [PubMed]
  3. Cognitive behavior therapy for Insomnia (CBT-I)
    1. Preferred first-line management
    2. Combines techniques
      1. Sleep Stimulus Control therapy
      2. Sleep Restriction Therapy
      3. Cognitive Restructuring
        1. Address maladaptive expectations and reduce anxiety about inadequate sleep
        2. Paradoxical intention
          1. Stay awake to reduce anxiety about not falling asleep
        3. Replace dysfunctional beliefs about sleep
          1. Reset expectation to 5-6 hours total sleep per night
          2. Support daytime function
      4. Typically also includes adjunctive measures
        1. Sleep Hygiene
        2. Relaxation Techniques (e.g. Progressive Relaxation)
    3. Refocuses attention on positive factors
      1. Turns off cycle: worrying about not sleeping
    4. Highly effective with long lasting effects (>2 years) when compared to medications (e.g. Ambien)
      1. Jacobs (2004) Arch Intern Med 164:1888-96 [PubMed]
      2. Trauer (2015) Ann Intern Med 163(3): 191-204 [PubMed]
      3. Morin (2015) Ann Intern Med 163(3): 236-7 [PubMed]
  4. Specific Techniques
    1. See Sleep Hygiene
    2. See Sleep Stimulus Control therapy
    3. See Sleep Restriction Therapy
    4. Relaxation Techniques
      1. See Relaxation Training
      2. See Progressive Relaxation
      3. Abdominal breathing
      4. Mindfulness and meditation
      5. Decrease physical tension and mental activity before bed
  • Management
  • Pharmacologic General Approach
  1. Start with non-pharmacologic measures as above
  2. Limit to short-term use (<3 months)
  3. Approach pharmacologic management based on Insomnia type
    1. Sleep-onset Insomnia (prolonged Sleep Latency)
      1. Melatonin (controlled release)
      2. Eszopiclone (Lunesta)
      3. Zaleplon (Sonata)
      4. Zolpidem (Ambien)
    2. Sleep-maintenance Insomnia
      1. Eszopiclone (Lunesta)
      2. Zolpidem (Ambien)
      3. Doxepin (Silenor)
    3. Insomnia in older adults
      1. Doxepin (Silenor)
      2. Melatonin (controlled release)
      3. Ramelteon (Rozerem)
    4. Insomnia with comorbid Major Depression
      1. Doxepin (Silenor)
      2. Mirtazapine (Remeron)
    5. Pregnancy
      1. Hydroxyzine 25 to 100 mg orally at bedtime
      2. Avoid Melatonin
        1. Crosses placenta and no available safety data
        2. Vine (2022) Braz J Psychiatry 44(3): 342-8 [PubMed]
      3. References
        1. Chaudhry (2018) Psychosomatics 59(4): 341-8 [PubMed]
  1. Precautions
    1. Exercise caution in the elderly due to Delirium, falls, Fractures and MVA risks (on Beers List)
      1. Avoid Benzodiazepines and Benzodiazepine analogs (e.g. Zolpidem) for longer than 3 months use
      2. (2013) Presc Lett 20(6): 33
    2. On average, Sedative-Hypnotics extend sleep time by only 30 minutes per night
    3. Risk of Benzodiazepine Dependence
    4. Even infrequent use of Sedative-Hypnotics increases mortality risk three-fold over baseline
      1. http://bmjopen.bmj.com/content/2/1/e000850
    5. Sedative-Hypnotic prescriptions increased 4 fold between 1999 and 2010
      1. Consider non-pharmacologic alternatives
      2. Ford (2014) Sleep 37(8): 1283-93 [PubMed]
  2. Mechanism
    1. Sedative-Hypnotics bind GABA Receptors which in turn inhibit central Neurons and their excitability
    2. Result in sedation, anxiolysis, Muscle relaxation and Retrograde Amnesia
    3. Nonbenzodiazepine hypnotics (e.g. Ambien) selectively bind sedation-related GABA subunits
  3. Indications: Short term Insomnia treatment
    1. Avoid use more than 3 weeks
    2. Start with lowest effective dose
    3. Taper slowly if longer use
  4. Contraindications
    1. Pregnancy and Lactation
    2. Sleep Apnea
    3. COPD
    4. Severe liver disease
    5. Severe Chronic Kidney Disease
  5. Adverse Effects (esp. Benzodiazepines)
    1. Daytime Somnolence
    2. Amnesia
    3. Early morning Insomnia
    4. Daytime anxiety and confusion
    5. Ataxia and falls in elderly
    6. Bioaccumulation in liver and Kidney disease (esp. elderly) with increased adverse effects
    7. Associated with decreased deep sleep time and secondary Fatigue (esp. with longterm use)
    8. Benzodiazepine Dependence
    9. Parasomnias (esp. higher at doses)
  6. Preparations: Benzodiazepine Receptor Agonists (Z-Drugs)
    1. Mechanism
      1. Z-Drugs selectively bind sub-parts of GABA Receptors
      2. Result in sedation without anxiolysis
    2. Short-acting agents
      1. Zolpidem (Ambien) 5 to 10 mg
        1. Used for initiating sleep and sleep maintenance
        2. Onset: 7 to 27 minutes
        3. Peak Activity: 1.6 hours
        4. Half-Life: 2 to 3 hours
      2. Zaleplon (Sonata) 5 to 20 mg
        1. Primarily effective for Sleep Latency (not sleep maintenance)
        2. May be helpful in early night awakening (4 hour duration)
        3. Onset: 30 minutes
        4. Peak Activity: 1 hour
        5. Half-Life: 1 hour
    3. Longer-acting agents (better sleep maintenance)
      1. Eszopiclone (Lunesta) 1 to 3 mg
        1. Associated with Dysgeusia in up to one third of patients
        2. Best evidence for continued effect with longterm use
        3. Onset: 10 minutes
        4. Peak Activity: 1 hour
        5. Half-Life: 5 to 7 hours
      2. Zolpidem CR (Ambien CR) 6.25 to 12.5 mg
        1. Unlikely to offer significant benefit over standard Zolpidem in sleep maintenance
        2. Onset: 30 minutes
        3. Peak Activity: 1.5 hours
        4. Half-Life: 3 hours (up to 4.5 hours)
    4. References
      1. Brandt (2017) Drugs R D 17(4): 493-507 [PubMed]
  7. Preparations: Benzodiazepines
    1. Temazepam (Restoril) 7.5 to 30 mg
      1. Onset: 30-60 minutes
      2. Half-Life: 8-15 hours
    2. Estazolam (Prosom) 0.5 to 2 mg
      1. Onset: 120 minutes
      2. Half-Life: 10-24 hours
    3. Triazolam (Halcion) 0.125 to 0.25 mg
      1. Onset: 15-30 minutes
      2. Half-Life: 2-5 hours
    4. Flurazepam (Dalmane) 15 to 30 mg
      1. Onset: 15 to 45 minutes
      2. Half-Life: 40 to 114 hours (mean 74 hours)
  1. Indications: Insomnia with comorbidity
    1. Major Depression
    2. Bruxism
    3. Fibrositis
    4. Hyperactivity history
  2. Adverse effects
    1. Anticholinergic side effects are common
    2. Long half lives lead to hangover effect in AM
  3. Mechanism
    1. Likely related to Antihistamine and Anticholinergic related sedation
  4. Preparations
    1. Doxepin (Adapin, Sinequan, Silenor) 3 to 6 mg orally at bedtime
      1. Only Tricyclic Antidepressant FDA approved for Insomnia
      2. Onset: 30 minutes
      3. Peak Activity: 3.5 hours
      4. Half-Life: 15 hours
    2. Trazodone (Desyrel) 50 to 150 mg at bedtime
      1. Peak Activity: 1 hour
      2. Half-Life: 10 hours
      3. Not recommended due to low efficacy and adverse effects including Fall Risk
        1. Increased Fall Risk applies to all sedating Antidepressants listed here (esp. Tricyclic Antidepressants)
        2. Sateia (2017) J Clin Sleep Med 13(2): 307-49 [PubMed]
    3. Amitriptyline (Elavil) 25 to 100 mg at bedtime
      1. Avoid Amitriptyline in elderly (Anticholinergic effects, see Beers List)
      2. Peak Activity: 4 hours
      3. Half-Life: 30 hours
    4. Mirtazipine (Remeron) 15-45 mg daily
      1. Peak Activity: 2 hours
      2. Half-Life: 30 hours
  1. Indications
    1. Insomnia in pregnancy (other agents are contraindicated in pregnancy)
  2. Adverse effects
    1. Anticholinergic adverse effects
    2. Paradoxical CNS Agitation may occur
    3. Exacerbates Restless Leg Syndrome
  3. Preparations
    1. Hydroxyzine (Vistaril) 25 to 100 mg at bedtime (often used for sleep in pregnancy)
    2. Diphenhydramine (Benadryl) 25 to 50 mg at bedtime
    3. Doxylamine (Unisom) 12.5 to 25 mg at bedtime
  1. Precautions
    1. Avoid use for Insomnia (numerous adverse effects, and poor evidence for benefit)
  2. Adverse effects
    1. Numerous (see Antipsychotics)
  3. Indications
    1. Refractory Insomnia
  4. Preparations
    1. Olanzapine (Zyprexa) 2.5 mg at bedtime (max: 20 mg)
    2. Quetiapine (Seroquel) 50 mg at bedtime (max: 400 mg)
    3. Risperidone (Risperdal) 0.25 mg at bedtime (max: 6 mg)
  1. Precautions
    1. FDA Schedule IV Agent (as with other Nonbenzodiazepine Sedative-Hypnotic agents)
    2. Very expensive ($12 to $15 per dose)
  2. Indications
    1. Refractory Insomnia (sleep maintenance or sleep onset)
  3. Mechanism
    1. Orexin (hypocretin) is a Neurotransmitter that binds orexinergic Neurons, promoting arousal and wakefulness
    2. Antagonists block Orexin by reversibly binding orexin receptors
  4. Efficacy
    1. Reduce time to sleep onset by 5 to 10 minutes and increase sleep duration by 15 to 20 minutes
  5. Adverse Effects
    1. Daytime Somnolence
  6. Agents
    1. Quviviq (Daridorexant) 25 to 50 mg orally at bedtime
      1. Peak Activity: 1 hour
      2. Half-Life: 8 hours
    2. Belsomra (Suvorexant) 10 to 20 mg orally at bedtime
      1. Onset: 30 minutes
      2. Peak Activity: 2 hours
      3. Half-Life: 12-15 hours
    3. Dayvigo (Lemborexant) 5 to 10 mg orally at bedtime
      1. More potent than Belsomra (Suvorexant), and best efficacy data
      2. Onset: 15 to 20 minutes
      3. Peak Activity: 1 hour
      4. Half-Life: 17 to 19 hours
  7. References
    1. Khazaie (2022) Front Psychiatry 13:1070522 +PMID: 36578296 [PubMed]
    2. Scammell (2011) Annu Rev Pharmacol Toxicol 51:243-66 +PMID: 21034217 [PubMed]
  1. Valerian Root
  2. Melatonin
    1. Helpful in initiating sleep, not in maintaining sleep (extending sleep duration)
    2. Night Shift Workers
      1. Start with 3 mg prior to daytime sleep (may increase to 5 mg)
    3. Sleep onset Insomnia
      1. Start with 3 mg at 30 to 60 minutes before bedtime (may increase to 5 mg)
    4. Elderly patients (including hospitalized or in long-term care facilities)
      1. Start 0.5 mg orally before bedtime
  3. Ramelteon (Rozerem) 8 mg
    1. Onset: 45 minutes
    2. Half-Life: 2 to 5 hours
    3. Melatonin receptor Agonist
    4. May be more effective in shifted sleep phase
  4. Tasimelteon (Hetlioz)
    1. Very expensive agent
    2. FDA approved for non-24 hour sleep-wake disorder
  • Management
  • Bright Light Exposure
  1. Mechanism
    1. Bright lights reset circadian rhythm
    2. Bright light sources
      1. Outdoor light
      2. Light box
  2. Indications
    1. Delayed Sleep Phase
      1. Young adults who do not get sleepy until midnight
      2. Use bright light in early morning (6 to 7 am)
    2. Early Sleep phase
      1. Elderly have onset of Tiredness at 6 pm
      2. Use bright light in late afternoon
  • Management
  • Anti-Seizure medications
  1. Indications
    1. Intermittent Insomnia
    2. Insomnia with comorbid depression
    3. Insomnia with comorbid Restless Legs Syndrome
  2. Efficacy
    1. Improves total sleep time by 46 to 64 minutes per day
      1. Dooley (2007) Trends Pharmacol Sci 28(2): 75-82 [PubMed]
  3. Preparations
    1. Gabapentin (Neurontin) 300-600 mg orally at bedtime
    2. Pregabalin (Lyrica) 50 mg orally at bedtime (up to 300 mg at bedtime)
  • Complications
  1. Neurocognitive effects
    1. Decreased concentration
    2. Decreased memory
    3. Altered behavior
    4. Decreased work performance and increased absenteeism
    5. Increased Motor Vehicle Accidents and work accidents
    6. Cognitive decline in over age 65 years (especially men)
      1. Insomnia is an independent risk factor
      2. Cricco (2001) J Am Geriatr Soc 49:1185-9 [PubMed]
  2. Psychiatric effects
    1. Overall quality of life reduced
    2. Increased Anxiety Disorder and Major Depression
    3. Substance Abuse and relapse
  3. Other associated conditions
    1. Cardiovascular Disease (e.g. Hypertension, Coronary Artery Disease)
    2. Decreased immune function (increased infection risk)
  • Resources
  • Non-medical Books
  1. Bishop (2000) Hello Midnight: Insomniac's ... Companion
    1. Paid link to Amazon.com (ISBN 0684848341)
  • References
  1. De Crescenzo (2022) Lancet 400(10347): 170-84 [PubMed]
  2. Edinger (2021) J Clin Sleep Med 17(2):255-62 +PMID: 33164742 [PubMed]
  3. Holbrook (2000) CMAJ 162: 216-20 [PubMed]
  4. Holder (2022) Am Fam Physician 105(4): 397-405 [PubMed]
  5. Kupfer (1997) N Engl J Med 336:341-6 [PubMed]
  6. Maness (2015) Am Fam Physician 92(12): 1058-64 [PubMed]
  7. Masters (2014) Ann Intern Med 161(7): ITC1-15 +PMID:25285559 [PubMed]
  8. Matheson (2017) Am Fam Physician 96(1): 29-35 [PubMed]
  9. Matheson (2024) Am Fam Physician 109(2): 154-60 [PubMed]
  10. Ramakrishnan (2007) Am Fam Physician 76(4):517-28 [PubMed]
  11. Sateia (2004) Med Clin North Am 88:567-96 [PubMed]