Pharmacologic Management of Insomnia

8/12/2019 Pharmacologic Management of Insomnia

1/28

Pharmacologic Management

of Insomnia


2/28

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


3/28

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.


4/28

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.


5/28

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.


6/28

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.


7/28

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.


8/28

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



9/28

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



10/28

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



11/28

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.


12/28

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


13/28

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



14/28

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



15/28

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.


16/28

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



17/28

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



18/28

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


19/28

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



20/28

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.


21/28

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


22/28

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.


23/28

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



24/28

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



25/28

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


26/28

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


27/28

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


28/28

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.

Documents

Pharmacologic Management of Insomnia