eMedicine Specialties > Pulmonology > Sleep-Related Disorders

Insomnia: Treatment & Medication

Author: Peter Smethurst, MD, Attending Physician, Pulmonary, Critical Care and Sleep Medicine, St Joseph's Medical Center
Coauthor(s): Silverio M Santiago, MD, Clinical Professor of Medicine, University of California at Los Angeles School of Medicine; Chief, Department of Pulmonary and Critical Care Medicine, Medical Director, Sleep Disorders Center, Veterans Affairs Medical Center of West Los Angeles; James A Rowley, MD, Associate Professor, Fellowship Program Director, Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine
Contributor Information and Disclosures

Updated: Jul 25, 2008

Treatment

Medical Care

The management of insomnia varies depending on the underlying etiology.

• If the patient has a medical, neurologic, or sleep disorder, direct treatment at the disorder. In particular, adequate pain control can greatly relieve the insomnia associated with pain syndromes.
• If the patient has a psychiatric disorder, direct treatment at the disorder. This may involve medications, psychotherapy, and possible referral to a psychiatrist, psychologist, or therapist.
• If the insomnia is related to medication or drug abuse, withdrawing the offending medication or drug is appropriate therapy.
• The treatment of psychophysiologic insomnia begins with an educational discussion about sleep and adequate sleep hygiene. The elements of good sleep hygiene are described in Patient Education.
• Before instituting therapy, most patients are asked to keep a sleep log for 2-4 weeks. This log, in which the patient records bed and wake times, sleep duration, and daytime naps and activities, gives a clearer picture of the degree of sleep disturbance and allows development of a tailored treatment.
• Cognitive-behavioral therapy is now considered the most appropriate treatment for patients with primary insomnia. Therapy is based on the fact that primary insomnia is associated with physiologic, emotional, and cognitive arousal and conditioning to arousal in bed. Cognitive therapy methods include cognitive relearning in which anxiety-producing beliefs about sleep and sleep loss are targeted. The 3 primary behavioral therapies are as follows:
  • Relaxation therapies
    • In progressive relaxation, the patient is taught to recognize and control tension through a series of exercises that consist of first tensing and then relaxing each muscle group in a systematic way.
    • Guided imagery and meditation teach the patient how to focus on neutral or pleasant targets in place of racing thoughts.
    • Biofeedback techniques can also be used. They have the advantage of providing patients with immediate feedback regarding their levels of tension and more quickly teaching them how to relax.
  • Stimulus control therapy: This therapy works to reassociate the bed with sleepiness instead of arousal. Rules for its use include the following:
    • The patient uses the bed only for sleeping and sexual activity (no reading, television, eating, or working in bed).
    • The patient lies down only when sleepy.
    • If the patient is unable to fall asleep in 15-20 minutes, he or she leaves the bed to do something relaxing until sleepy.
    • The previous step is repeated as often as necessary.
    • The patient does not spend more time in bed than is needed.
  • Sleep-restriction therapy: This therapy is based on the fact that excessive time in bed often perpetuates insomnia. Limiting the time in bed leads to more efficient sleep that is both consolidated and more regular and predictable. Time in bed is allowed to increase as the patient demonstrates a continuing ability to sleep in an efficient and consolidated fashion.

Consultations

Primary care providers should be able to diagnose and treat transient or short-term insomnia. Chronic insomnia is often more difficult to treat, and when primary or associated with a sleep or psychiatric disorder, referral to an appropriate specialist may be indicated.

• Patients should be referred to a sleep specialist in the following situations:
  • If any elements of the history suggest obstructive sleep apnea or RLS/PLMD
  • In cases of chronic insomnia, particularly if it is psychophysiological insomnia
• Many sleep centers have a staff psychologist who specializes in treating insomnia. The advantages include experience in behavioral techniques and in providing sleep education, greater available time for the often-frequent follow-up care that is needed, and the ability to ascertain if other psychological factors may need further evaluation by a psychiatrist.
• Refer patients with a history of depression to a psychiatrist based on the usual referral pattern of the primary care provider.

Medication

Importantly, note that medications alone do not cure insomnia; however, they may provide symptomatic relief and should be used as an adjunct to nonpharmacologic therapy.

Historically, sedative hypnotics and antidepressants have been used as first-line prescription medications for insomnia. Over-the-counter (OTC) medications that patients may try include antihistamines and melatonin. More recently, ramelteon (Rozerem), a melatonin receptor agonist, has been approved for the treatment of insomnia.

• Therapy should be instituted with a small dose and maintained at the smallest effective dose.
• Continued nightly use should be avoided; patients should be encouraged to use them only when truly necessary.
• Use for more than 2-3 weeks should be avoided.
  
• A hypnotic free of residual effects in the morning is preferable (eg, zolpidem, zaleplon).
  
• Hypnotics with a rapid onset of action, such as zolpidem or zaleplon are preferable when the problem is falling asleep. If the problem is staying asleep, a hypnotic with a slower rate of elimination may be more appropriate (eg, temazepam, estazolam, flurazepam). If the patient is depressed, an antidepressant with sedative properties, such as trazodone or amitriptyline, may be useful.
  
• Hypnotics should never be used with alcohol.
  
  
• In general, pregnancy is a contraindication.
  
  
• Benzodiazepines should be avoided in patients with known or possible sleep apnea.
  
• Smaller doses should be used in elderly patients.
  
• In most patients, the risk of dependency is low (most rarely escalate the dose or use more frequently than prescribed). However, avoid use in patients with a history of substance abuse.
  
• Rebound insomnia may develop when the medication is abruptly withdrawn. This is more likely to occur with larger doses and with the short-acting agents. Using smaller doses and tapering the drug can avoid rebound insomnia.

Note that most studies of the efficacy of sedative-hypnotics have been short-term trials (ie, generally <4 wk). Use for longer than 4 weeks was thought to result in tolerance and decreased efficacy, though supportive findings are scarce, and epidemiologic literature suggests that patients report continued efficacy with continued use. However, because of the addictive nature of benzodiazepines, most authorities believe that the duration of use should be limited.

A newer drug, eszopiclone, was the first sedative-hypnotic to be tested over a 6-month period and showed continued efficacy over the 6-month period.³ More recent data show continued efficacy at up to 12 months.

Common OTC antihistamines (eg, diphenhydramine, hydroxyzine) are not indicated for the treatment of sleeplessness. Antihistamines are the major ingredient of OTC sleep aids and are the ingredient in cold and sinus formulas sold as bedtime-use medications. While H1 antihistamines have sedative effects in healthy individuals, no study has established a dose range over which the hypnotic effect is effective in patients with insomnia. Thus, their regular use in individuals with insomnia is not advised. These agents may have some subjective benefit, but long-term efficacy has not been demonstrated and they are not recommended.

Melatonin has also become a popular OTC sleep aid. Melatonin is a naturally occurring hormone secreted by the pineal gland. The concentration of melatonin is highest in the blood during normal times of sleep and lowest during normal times of wakefulness. The general consensus is that melatonin given during normal waking hours has hypnotic properties. Most studies of melatonin have been small and of limited duration, and the results have conflicted somewhat with several studies that have shown limited or no effect. Most of the data, however, seem to suggest that melatonin taken before bedtime decreases sleep latency and may increase total sleep time.^4,5

Studies of melatonin in individuals with chronic insomnia have not demonstrated objective changes in patient sleep habits or changes in mood or alertness the day after treatment. In addition, a dose-response relationship has not been determined. OTC melatonin is also sold at doses much higher than those that naturally occur in the blood. Therefore, at this time, most authorities do not recommend melatonin for the treatment of chronic insomnia.

Ramelteon, a melatonin receptor agonist, has been approved by the US Food and Drug Administration for use in persons with insomnia. It has been shown to have no potential for abuse and, as such, is the first nonscheduled prescription drug available in the United States for the treatment of insomnia.

Alternative and herbal medications have also been tried in the treatment of insomnia. Among the most widely used and studied of these is valerian root extract. A 2006 meta-analysis of 16 randomized controlled trials of valerian for the treatment of insomnia had conflicting results.⁶ The pooled data did seem to show evidence of improved sleep; however, the authors noted a possible publication bias that may have contributed to this result.

Nonbenzodiazepine hypnotics

Good choice for treatment of sleep-onset insomnia.

Eszopiclone (Lunesta)

Nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. Precise mechanism of action unknown but believed to interact with GABA receptor at binding domains close to or allosterically coupled to benzodiazepine receptors.
Indicated for insomnia to decrease sleep latency and improve sleep maintenance. Short half-life (6 h). Higher doses (ie, 2 mg for elderly and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses are (ie, 1 mg for elderly and 2 mg for nonelderly adults) are suitable for difficulty falling asleep.

Zaleplon (Sonata)

Nonbenzodiazepine hypnotic from the pyrazolopyrimidine class. Preferentially binds to the omega-1 receptor of the GABA receptor family. Rapid onset of action with ultrashort duration of action. Good choice for treatment of sleep-onset insomnia.

Zolpidem (Ambien, Ambien CR)

Sedative hypnotic of imidazopyridine class. Structurally dissimilar to benzodiazepine but similar in activity with the exception of reduced effects on skeletal muscle and seizure threshold. Has rapid onset and duration of action.
Good first choice for sleep-onset insomnia. ER product (Ambien CR) consists of a coated 2-layer tab and is useful for insomnia characterized by difficulties with sleep onset and/or sleep maintenance. First layer releases drug content immediately to induce sleep; second layer gradually releases additional drug to provide continuous sleep.

Benzodiazepine hypnotics

Hypnotics of choice for many years because of their relative safety compared with barbiturates.

Estazolam (ProSom)

Intermediate-acting benzodiazepine good for sleep maintenance. Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Half-life is 10-24 h, and peak action is 2 h.

Temazepam (Restoril)

Short-to-intermediate acting with longer latency to onset and half-life. May be more helpful in sleep-maintenance insomnia. Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.

Antidepressants

Adverse effect of drowsiness observed with some antidepressants can be used to benefit the patient in treatment of sleep-maintenance insomnia or insomnia associated with depression.

Amitriptyline (Elavil)

TCA with sedative effects. Blocks reuptake of norepinephrine and serotonin, which increases concentration in the CNS. Highly anticholinergic. Often discontinued because of somnolence and dry mouth.
Cardiac arrhythmia, especially in overdose, has been described; monitoring the QTc interval after reaching the target level is advised. Up to 1 mo may be needed to obtain clinical effects.

Mirtazapine (Remeron)

Exhibits both noradrenergic and serotonergic activity. In cases of depression associated with severe insomnia and anxiety, shown to be superior to other SSRI drugs.

Trazodone (Desyrel)

Non-TCA with short onset of action. Consolidates sleep. Antagonist at 5-HT2 receptor and inhibits reuptake of 5-HT. Also has negligible affinity for cholinergic and histaminergic receptors.

Melatonin agonists

Indicated for insomnia characterized by difficulty with sleep onset.

Ramelteon (Rozerem)

Melatonin receptor agonist with high selectivity for human melatonin MT₁ and MT₂ receptors. MT₁ and MT₂ are thought to promote sleep and be involved in maintenance of circadian rhythm and normal sleep-wake cycle. Indicated for insomnia characterized by difficulty with sleep onset.

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