Pharmacologic Management of Insomnia
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Transcript of Pharmacologic Management of Insomnia
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Pharmacologic Management
of Insomnia
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Overview
Introduction
Definitions
Sleep Patterns in Insomnia
Types of Insomnia
Contributing Factors to Development
Effects and Consequences
Differential Diagnosis
Indications for Treatment
Treatment Goals
Treatment Overview Treatment Options
Selection of Treatment Agent
Insomnia in the Elderly
General Cautions
Conclusion
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Introduction
Approximately 1/3 of the US population complainsof insomnia
More than 40% of individuals suffering frominsomnia self medicate with OTC medications or
other substances such as alcohol
Insomnia has historically been viewed as asymptom secondary to a medical condition but is
now recognized as an independent disorder
William A. Kehue. General Psychiatry. In: Bressler L, Deyoung, G.R., El-Ibiary,S.,et al. Updates in Therapeutics: The Pharmacotherapy Preparatory
Course, 2010 ed. Lenexa, KS: American College of Clinical Pharmacy 2010:331-335.
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Definitions
NHLBI: Subjective patient complaint of difficulty falling
asleep, difficulty staying asleep, poor quality sleep, or
inadequate sleep despite adequate opportunity
DSM-IV definition
Difficulty initiating or maintaining sleep for at least 1 month Nonrestorative sleep persisting for at least 1 month
Accompanied by clinically significant impairment in daytime
functioning
Research criteria Sleep latency > 30 minutes
Sleep efficiency < 85%
Sleep disturbance > 3 times per week
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep
Med 2008 Oct 15;4(5):487-504.
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Sleep Patterns in Insomnia
Sleep onset insomnia
Difficulty falling asleep
Longer time to sleep onset
Sleep maintenance insomnia
Difficulty staying asleep
Frequent nocturnal awakenings
Sleep offset insomnia
Waking too early in the morning
Non-restorative sleep
Fatigue despite adequate sleep duration
Kryger MH, Roth T, Dement WC, et al. Principals and Practice of Sleep Medicine. Philadelphia, PA: Elsevier Saunders; 2005.
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Types of Insomnia
Type Duration Likely Causes
Transient 2 3 daysAcute situation
Environmental stressors
Short term < 3 weeksMajor life event
Substance abuse
Chronic > 3 weeksPsychiatric illness
Medical causeschronic illnessPrimary sleep disorder
Transient: usually resolves when acute stressors are eliminated;pharmacotherapy for a few days is an option
Short Term: may be due to stressor of ongoing nature; sleep hygieneimportant, pharmacotherapy may be used (intermittent basis)
Chronic: treat any underlying condition(s) that may be causing insomnia;initiate good sleep hygiene practice and pharmacotherapy
indicated for long term use
William A. Kehue. General Psychiatry. In: Bressler L, Deyoung, G.R., El-Ibiary,S.,et al. Updates in Therapeutics: The Pharmacotherapy Preparatory Course,
2010 ed. Lenexa, KS: American College of Clinical Pharmacy 2010:331-335.
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Contributing Factors to Development
Predisposing factors
Personality
Sleep-wake cycle
Circadian rhythm
Coping mechanisms Age
Perpetuating factors
Conditioning
Substance abuse
Performance anxiety
Poor sleep hygiene
Precipitating factors
Situational
Environmental
Medical
Psychiatric
Medications
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
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Effects and Consequences
Worsens psychiatricdisorders
Prolongs medical
illnesses
Reduced quality of life Higher absenteeism
Increased accident risk
Higher health care costs
Cognitive impairment
Fatigue Moodiness
Irritability or anger
Daytime sleepiness
Anxiety about sleep
Lack of concentration
Poor memory
Lack of motivation orenergy
Headaches or tension
Kryger MH, Roth T, Dement WC, et al. Principals and Practice of Sleep Medicine. Philadelphia, PA: Elsevier Saunders; 2005.
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Differential Diagnosis
Conditions Hyperthyroidism
Pain
Cardiovascular disease
Heartburn (GERD)
Neurological Disorders
Diabetes
Menopause BPH
Psychological
Alcohol
Caffeine/chocolate
Nicotine/nicotine patch
BBs
CCBs
Bronchodialators
Corticosteriods
Decongestants
Antidepressants
Thyroid hormones
Medications
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
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Indications for Treatment
Treatment is recommended when the chronic insomnia hasa significant negative impact on a patients:
Sleep quality
Health
Co-morbid conditions Daytime function
Recognize and treat co-morbid conditions that commonly
occur with insomnia
Identify and modify behaviors and medications/substances
that impair sleep
Kryger MH, Roth T, Dement WC, et al. Principals and Practice of Sleep Medicine. Philadelphia, PA: Elsevier Saunders; 2005.
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Treatment Goals
Primary Goals: Improvement in sleep quality and time
Improvement of insomnia-related daytime impairments
Other Goals:
Decreased frequency of awakenings
Decrease in sleep related complaints Improvement in sleep related psychological distress
Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep
Med 2008 Oct 15;4(5):487-504.
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Treatment Overview
Nonpharmacologic Therapy Sleep Hygiene Cognitive behavioral therapies
Pharmacologic Therapy
Nonprescription agents
Anti-histamines
Herbal supplements
Prescription agents Antidepressants
Antipsychotics
Benzodiazepine-receptor agonists
Melatonin-receptor agonists
Benzodiazepines
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Sleep Hygiene
Dont go to bed unless you are sleepy
Get up at the same time every morning
Get a full nights sleep on a regular basis (usually 7-8 hours for adults)
Avoid taking naps if you can
Keep a regular schedule
Dont read, eat, watch TV, or talk on the phone
Do not have any caffeine after lunch
Do not have any alcohol within six hours of your bedtime
Avoid smoking in the evening and right before bedtime
Do not go to bed hungry
Dont eat a big meal near bedtime either
Avoid any tough exercise within six hours of your bedtime
Avoid sleeping pills, or use them cautiously
Try to get rid of or deal with things that make you worry
Make your bedroom quiet, dark, and a little bit cool
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
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First Generation Antihistamine
diphenhydramine (Benadryl
) No recent data of efficacy over 3 weeks; tolerance within a few days
Rapid tolerance to sedating effects
Not for use in elderly patients
Potential adverse effects
Residual effects
Delirium
Dry mouth
Constipation
Blurred vision
Urinary retention
Narrow angle glaucoma exacerbation
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
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Herbal Products
Melatonin Valerian
Not recommended in the treatment of chronic insomnia dueto the relative lack of efficacy and safety data
Contamination with unknown substances is a problem with
natural remedies
Bonnet MH, Arand DL. Treatment of Insomnia. In: UpToDate; 2010. Available at: http://www.uptodate.com. Accessed December 9, 2010.
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Antidepressants
trazadone doxepine amitriptyline
Limited amount of data
Sedating properties due to central anticholinergic and antihistaminergic activity
Sedating antidepressants useful in the treatment of insomnia associated with
depression
Doses required for insomnia usually lower than doses used for depression
Efficacy not entirely established in trials
Routine use of sedating antidepressants (except low dose doxepine) is not
recommended Sedating effect has tendency to be short-lived
Side effects common
Bonnet MH, Arand DL. Treatment of Insomnia. In: UpToDate; 2010. Available at: http://www.uptodate.com. Accessed December 9, 2010.
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Atypical Antipsychotics
quetiapine (Seroquel
) Emerging case reports for PTSD and anxiety
Lack of data regarding the use for insomnia
Option for patients with PTSD, at risk for addiction, and in the presence ofagitation or psychosis
Adverse effects: danger of precipitating weight gain, metabolic syndrome, or
other adverse effects
Doses typically significantly lower for the treatment of insomnia than for primaryindications
Unknown safety and efficacy of these agents when used off-label for the
treatment of insomnia
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
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Benzodiazepine Receptor Agonists
zolpidem (Ambien
) Short-term treatment Sleep onset insomnia
zolpidem ER (Ambien CR)
Not limited to short-term use Sleep onset AND sleep maintenance
zaleplon (Sonata) Short-term treatment
Sleep onset insomnia
eszopiclone (Lunesta) Not limited to short-term use
Sleep onset AND sleep maintenance
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Benzodiazepine Receptor Agonists
Tolerance and abuse have not been shown to be amajor problem in the general population
Generally have shorter duration of action than most
benzodiazepines less likely to cause next day sedation
Side effects include:
Drowsiness
Dizziness
Unsteadiness of gait
Rebound insomnia
Memory impairment
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
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Melatonin Receptor Agonist
Ramelteon (Rozerem)
FDA-approved for sleep onset insomnia
Not limited to short-term use
Little abuse potential
Not a DEA controlled substance
No rebound insomnia or withdrawal upon discontinuation
Adverse events
Somnolence Dizziness
Fatigue
Avoid in hepatic impairment
Absolute Contraindication: co-administration with fluvoxamineBonnet MH, Arand DL. Treatment of Insomnia. In: UpToDate; 2010. Available at: http://www.uptodate.com. Accessed December 9, 2010.
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Benzodiazepines
triazolam (Halcion)*
temazepam (Restoril)*
estazolam (ProSom)*
flurazepam (Dalmane)*
quazepam (Doral
)*
clonazepam (Klonopin)
lorazepam (Ativan)
diazepam (Valium)
alprazolam (Xanax)
* marketed for use as sedative-hypnotic agents
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Benzodiazepines
Generally safe, effective, and well tolerated by patients
All members of this class can be used as sedatives, but only 5 are
marketed for this indication
Used as sedative-hypnotics due to:
Rapid absorption CNS actions produced quickly
Problems with benzodiazepines
Tolerance
Potential for abuse
Residual daytime sedation
Rebound insomnia
Anteriograde amnesia
Caution in elderly patients
Withdrawal
William A. Kehue. General Psychiatry. In: Bressler L, Deyoung, G.R., El-Ibiary,S.,et al. Updates in Therapeutics: The Pharmacotherapy Preparatory Course,
2010 ed. Lenexa, KS: American College of Clinical Pharmacy 2010:331-335.
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Discontinuation Effects on Sleep
Hypnotic Agents Rebound insomnia
Single symptom
Exacerbation relative to baseline
1-2 night duration
Using smaller doses and tapering the drug can avoid
rebound insomnia
Withdrawal syndrome Return of original symptom(s)
At basal level of severity
Longer duration
National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
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Selection of Treatment Agent
Mainly based on the type of insomnia (sleep onset, sleep maintainence)
and duration of effect
Sleep Onset Insomnia
Short-acting medication
zaleplon, zolpidem, ramelteon
Sleep Maintenance Insomnia
Longer-acting medication
zolpidem ER, eszopiclone, temazepam, estazolam, low dose doxepin
Consideration of specific agent also includes adverse effects, patient
specific concerns, and cost
Bonnet MH, Arand DL. Treatment of Insomnia. In: UpToDate; 2010. Available at: http://www.uptodate.com. Accessed December 9, 2010.
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Insomnia in the Elderly
Sleep quality declines with age
Insomnia not always due to aging
Multiple factors affect sleep in the elderly
Nocturia
Pain syndromes Medical disorders
Nonpharmacologic treatment should take precedence over
pharmacologic treatment
Hypnotics should be prescribed in lower doses than doses prescribed inyounger patients
Drugs tend to have longer duration of effect due to changes in metabolism and
elimination
Increased incidence of falls and bone fractures (especially at night)
Passaro EA. Insomnia: Follow-up. Medscape. Available at http://emedicine.medscape.com/article/1187829-followup. Accessed 12/02/2010.
http://emedicine.medscape.com/article/1187829-followuphttp://emedicine.medscape.com/article/1187829-followuphttp://emedicine.medscape.com/article/1187829-followuphttp://emedicine.medscape.com/article/1187829-followup -
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General Cautions
The smallest effective dose should always be used in therapy
Hypnotics should never be used with alcohol since this can produce
excess sedation
Smaller doses should be used in elderly patients, and used verycautiously, if at all, in patients with risk of falls
Caution with use in patients with a history of substance abuse
Rebound insomnia may develop when the medication is withdrawn
abruptly in some patients
Some OTC medications like PM medications contain more than one
medication
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Conclusion
Insomnia is common condition, often co-morbid with other conditions and
associated with significant morbidities
Impairments in daytime functioning, increase in risk for psychiatric illness,
including depression, anxiety and other conditions are consequences of insomnia
Good sleep hygiene should be emphasized to all patients
Many of the most common drugs for insomnia are not FDA approved for that
purpose
Limited duration of studies for insomnia medications
No drug for insomnia is completely safe or free of the risk of side effects
In the absence of evidence, need to match nature of sleep problem with
treatment, availability, cost tolerance, side effect tolerance, and co-morbid
conditions
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References
1. William A. Kehue. General Psychiatry. In: Bressler L, Deyoung, G.R., El-Ibiary,S.,et al. Updates in
Therapeutics: The Pharmacotherapy Preparatory Course, 2010 ed. Lenexa, KS: American College of ClinicalPharmacy 2010:331-335.
2. National Institute of Health Statement Regarding the Treatment of Insomnia. Sleep. 2005;28:1049-1057.
3. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management
of chronic insomnia in adults. J Clin Sleep Med 2008 Oct 15;4(5):487-504.
4. Kryger MH, Roth T, Dement WC, et al. Principals and Practice of Sleep Medicine. Philadelphia, PA: Elsevier
Saunders; 2005.
5. Morgenthaler T, Kramer M, Alessi C, Friedman L, Boehlecke B, Brown T, Coleman J, Kapur V, Lee-Chiong T,Owens J, Pancer J, Swick T, American Academy of Sleep Medicine. Practice parameters for the psychological
and behavioral treatment of insomnia: an update.
6. Bonnet MH, Arand DL. Treatment of Insomnia. In: UpToDate; 2010. Available at: http://www.uptodate.com.
Accessed December 9, 2010.
7. Kryger MH, Roth T, Dement WC, et al. Principals and Practice of Sleep Medicine. Philadelphia, PA: Elsevier
Saunders; 2005.