Pharmacologic Treatments of Insomnia

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Review Addresses Pharmacologic Treatments of Insomnia

CME/CE

News Author: Laurie Barclay, MD

CME Author: Vega, MD

August 17, 2007 — A review in the August 15 issue of American Family Physician

discusses various treatment options for insomnia, including tips for

appropriate times to prescribe hypnotics and other pharmacologic

treatments.

"The American Academy of Sleep Medicine defines

insomnia as unsatisfactory sleep that impacts daytime functioning,"

write Kalyanakrishnan Ramakrishnan, MD, and Dewey C. Scheid, MD, MPH,

from the University of Oklahoma Health Sciences Center in Oklahoma

City. "More than one third of adults report some degree of insomnia

within any given year, and 2 to 6 percent use medications to aid sleep.

Insomnia is associated with increased morbidity and mortality caused by

cardiovascular disease and psychiatric disorders and has other major

public health and social consequences, such as accidents and

absenteeism."

The need to evaluate and treat insomnia depends in

large measure on how often sleep is disrupted and on how much insomnia

affects daytime functioning. Although treating insomnia on the first

visit without further evaluation may be appropriate for patients

experiencing grief or other clear acute stressor, severe or

long-lasting insomnia mandates a complete workup. This evaluation

should focus on underlying medical, neurologic, or psychiatric

conditions.

Criteria for the diagnosis of insomnia should include

1 or more of the following symptoms: difficulty falling and staying

asleep, poor quality of sleep, difficulty sleeping despite adequate

opportunity and circumstances for sleep, and/or awakening too early.

In

addition, patients diagnosed with insomnia should have 1 or more of the

following types of daytime impairment caused by disturbances in sleep:

impairment of attention, concentration, or memory; concerns or anxiety

regarding sleep; daytime sleepiness; making errors or having motor

crashes or mishaps while working; fatigue or malaise; gastrointestinal

symptoms; absent motivation; irritability or disturbances in mood; poor

performance in school, at work, or in social settings; and/or tension

headaches.

"Ideally, treatment for insomnia would improve sleep

quantity and quality, improve daytime function (greater alertness and

concentration), and cause minimal adverse drug effects," the study

authors write. "Most experts recommend starting with nonpharmacologic

therapy.... Behavioral and cognitive interventions have minimal risk of

adverse effects, but disadvantages include high initial cost, lack of

insurance coverage, few trained therapists, and decreased effectiveness

in older adults."

Initial treatment options should include

nonpharmacologic therapy, education regarding sleep hygiene, and proper

attention to exercise, which has been shown in some trials to improve

sleep as effectively as do benzodiazepines. The efficacy of cognitive

behavior therapy (CBT) for insomnia is well documented.

When

hypnotics are needed, the frequency and duration of use should be

individualized based on each patient's specific circumstances. As a

general rule, they should be prescribed only for short periods.

Over-the-counter antihistamine preparations should only be used on

occasion and not routinely. Because of its potential for abuse, alcohol

should not be used to treat insomnia.

Opiates may be helpful for

insomnia caused by pain. For short-term treatment, benzodiazepines may

be indicated, but long-term use may be associated with adverse effects

and withdrawal symptoms. For long-term treatment of chronic insomnia,

the newer-generation nonbenzodiazepines, such as zolpidem, zaleplon,

eszopiclone, and ramelteon, have a better safety profile and therefore

are more effective first-line treatment options.

Specific clinical recommendations are as follows:

Effective, nonpharmacologic treatments for chronic insomnia are exercise, CBT, and relaxation therapy (level of evidence, A).

In

patients with sleep disorders that involve circadian rhythm, melatonin

is effective and safe for short-term treatment (level of evidence, .

Although

benzodiazepines are effective for treating chronic insomnia, they have

significant adverse effects as well as the risk for patients becoming

dependent on their use (level of evidence, .

Based on

indirect comparisons, the nonbenzodiazepines are effective for chronic

insomnia and seem to have fewer adverse effects than benzodiazepines.

Examples of the nonbenzodiazepines include eszopiclone, zaleplon, and

zolpidem (level of evidence, .

Although little available

evidence supports combining nonpharmacologic and pharmacologic

treatments of insomnia, one study comparing benzodiazepine with CBT vs

benzodiazepine alone showed that combination therapy minimally improved

sleep efficiency, but not wakefulness after sleep onset or total sleep

time.

"Although substance abusers may abuse benzodiazepines, they

rarely abuse nonbenzodiazepines," the study authors conclude. "The cost

of nonbenzodiazepines is considerably higher than benzodiazepines. An

economic evaluation comparing the cost-effectiveness of

nonpharmacologic treatment, benzodiazepines, eszopiclone, and no

treatment in older adults found that, compared with benzodiazepines,

nonpharmacologic therapy (ie, CBT) produced a net gain of 0.37

quality-adjusted life-years at a savings of $2,781 over 10 years."

The authors have disclosed no relevant financial relationships.

Am Fam Physician. 2007;76:517-526, 527-528.

Learning Objectives for This Educational ActivityUpon completion of this activity, participants will be able to:

List the risk factors for chronic insomnia.Describe available treatments of insomnia.

Clinical Context

Insomnia is a very common condition in

adulthood. More than one third of adults experience some insomnia each

year, and up to 6% may use a medication to help them sleep. Chronic

insomnia is defined as insomnia lasting more than 30 days. Risk factors

for chronic insomnia include advanced age, female sex, lower

socioeconomic status, and unemployment. In addition, commonly used

medications, including selective serotonin reuptake inhibitors,

lamotrigine, phenytoin, atorvastatin, and oral contraceptives can

promote chronic insomnia.

There are many therapeutic options for patients with insomnia. The current article reviews these treatments.

Study HighlightsRelaxation therapy and CBT can improve sleep for the long term, and

regular exercise is encouraged to promote better sleep. Previously,

exercise has been demonstrated to be as effective as benzodiazepines

for insomnia.Over-the-counter antihistamines may be used by nearly one fourth of

patients with insomnia, but they generally should be avoided because of

poor efficacy and residual drowsiness.Considering alternative therapies, melatonin can improve insomnia

induced by changes in circadian schedule, such as jet lag and shift

work. Valerian root has minimal evidence of efficacy in treating

insomnia, and preparations may vary in the content of active medication.Because of tolerance and an increased risk for dependence and adverse events, barbiturates should be avoided as sleep aids.Some antidepressants, including amitriptyline, doxepin, trazodone,

and mirtazapine can decrease sleep-onset latency and improve total

sleep time and sleep quality. However, these antidepressants can

suppress rapid eye movement (REM) sleep. Their use should generally be

limited to patients with depression and insomnia.Benzodiazepines are best used for the short-term treatment of

insomnia. Tolerance and dependence can occur with prolonged use.

Withdrawal occurs in approximately 50% of patients receiving

benzodiazepines on a chronic basis.Nonbenzodiazepine hypnotics, such as zolpidem, zaleplon, and

eszopiclone, may have less impact on sleep architecture and may promote

less REM sleep rebound compared with benzodiazepines. Therefore, this

class of medications may be considered first-line treatments of chronic

insomnia. Zaleplon may be administered multiple times in 1 evening

because of its short (1 hour) half-life. Eszopiclone is the only

hypnotic agent with a US Food and Drug Administration indication for

use longer than 35 days.Ramelteon is a selective melatonin receptor agonist that reduces

sleep-onset latency and increases periods of sleep. Although ramelteon

may not promote abuse and dependence to the same degree as other

hypnotics, patient evaluations of the drug's efficacy have been

inconsistent.There is little evidence of synergy in combining CBT with medical

therapy for insomnia. However, available research suggests that these

treatments may be roughly equivalent in efficacy.

Pearls for PracticeRisk factors for chronic insomnia include advanced age, female sex,

lower socioeconomic status, and unemployment. In addition, commonly

used medications, including selective serotonin reuptake inhibitors,

lamotrigine, phenytoin, atorvastatin, and oral contraceptives can

promote chronic insomnia.The current review suggests that medications such as zolpidem,

zaleplon, and eszopiclone may be first-line medical treatments of

chronic insomnia, although CBT can also be effective for insomnia.

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