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Primary Insomnia Overview

Primary Insomnia Causes

Primary Insomnia Symptoms

Primary Insomnia Treatment

Insomnia Overview

Disorders That Disrupt Sleep (Parasomnias) Overview

Understanding Insomnia Medications

Sleep Disorders in Women Overview

Sleep Disorders and Aging Overview

Sleeplessness and Circadian Rhythm Disorder Overview




Author: Aparna Ranjan, MD, Palliative Medicine Physician, Associate Medical Director, Hospice and Palliative Medicine, Bon Secours Richmond Health System

Aparna Ranjan is a member of the following medical societies: American Geriatrics Society and American Medical Association

Coauthor(s): Angela Gentili, MD, Director of Geriatrics Fellowship Program, Associate Professor, Department of Internal Medicine, Virginia Commonwealth University Health System & McGuire VAMC; Kirk L Nelson, MD, Assistant Professor, Department of Psychiatry, Virginia Commonwealth University Medical College of Virginia; Sleep Laboratory Director, Mental Health Service Line, Veteran Affairs Medical Center, Richmond, Virginia

Editors: Jennifer S Berg, MD, Program Director, Department of Psychiatry, Naval Medical Center San Diego; Assistant Clinical Professor, Department of Psychiatry, University of California at San Diego; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Iqbal Ahmed, MBBS, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii; Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin; Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA

Author and Editor Disclosure

Synonyms and related keywords: sleeplessness, sleep disturbance, sleep apnea, psychophysiological insomnia, learned insomnia, behavioral insomnia, idiopathic insomnia, stress-related insomnia, sleep state misperception, persistent psychophysiological insomnia, sleep disorder

Background

Primary insomnia is sleeplessness that is not attributable to a medical, psychiatric, or environmental cause. The diagnostic criteria for primary insomnia (307.42) from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) are as follows:

  • The predominant symptom is difficulty initiating or maintaining sleep, or nonrestorative sleep, for at least 1 month.
  • The sleep disturbance (or associated daytime fatigue) causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  • The sleep disturbance does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or a parasomnia.
  • The disturbance does not occur exclusively during the course of another mental disorder (eg, major depressive disorder, generalized anxiety disorder, a delirium).
  • The disturbance is not due to the direct physiological effects of a substance (eg, drug abuse, medication) or a general medical condition.

The International Classification of Sleep Disorders does not recognize a category of primary insomnia but discusses the following 3 free-standing insomnia subgroups:

  • Psychophysiological insomnia
  • Idiopathic insomnia
  • Sleep state misperception

The disorder is chronic by definition (ie, lasting at least 1 mo).

Pathophysiology

Psychophysiological insomnia

The synonyms are learned insomnia or behavioral insomnia, when persistent.

The primary components involved are intermittent periods of stress, which result in poor sleep and generate 2 maladaptive behaviors, including (1) a vicious cycle of trying harder to sleep and becoming tenser, expressed by patients as "trying too hard to sleep," and (2) bedroom habits and routines and other sleep-related activities (eg, brushing teeth), conditioning the patient to frustration and arousal.

Bad sleep habits such as those naturally acquired during periods of stress are occasionally reinforced and, therefore, are not resolved and become persistent. Thus, the insomnia continues for years after the stress has abated and is labeled persistent psychophysiological insomnia.

Idiopathic insomnia

Lifelong sleeplessness is attributed to an abnormality in the neurologic control of the sleep-wake cycle involving many areas of the reticular activating system (promoting wakefulness) as well as in areas such as solitary nuclei, raphe nuclei, and medial forebrain area (promoting sleep).

Possibly, a so-called neuroanatomic, neurophysiologic, or neurochemical lesion exists in the sleep system in which patients tend to be on the extreme end of the spectrum toward arousal.

Sleep state misperception

The patient reports experiencing insomnia without objective evidence of any sleep disturbance.

Frequency

United States

Primary insomnia is diagnosed in approximately 15% of patients with insomnia who are referred to sleep disorder centers following exclusion of other predisposing conditions. However, true incidence is not known. Primary insomnia is estimated to occur in 25% of all patients with chronic insomnia.

Mortality/Morbidity

Whether the consequences associated with chronic insomnia outweigh the costs of treatment remains debatable. Despite that, the following associations have been noted:

  • Increased risk of mortality is associated with short sleep lengths.
  • Insomnia is the best predictor of the future development of depression.
  • Catastrophic worry about the consequences of not sleeping is common among patients with chronic insomnia and serves to maintain the sleep disturbance.
  • Increased risk exists of developing anxiety, alcohol and drug use disorders, and nicotine dependence.
  • Poor health and decreased activity occur.
  • Onset of insomnia in older patients is related to decreased survival.

Sex

Primary insomnia is more common in women than in men.

Age

Persons of any age may be affected, although primary insomnia is more common in the older population.



History

A thorough clinical interview with the patient and his or her sleep partner is critical in making the correct diagnosis of primary insomnia.

  • Psychophysiological insomnia
    • Sleep disturbance varies from mild to severe.
    • Insomnia may manifest as difficulty falling asleep or as frequent nocturnal awakenings.
    • Patients often find that they can sleep well anywhere else but in their own bedroom (see Pathophysiology).
    • Patients with this type of insomnia tend to be more tense and dissatisfied compared to people who sleep well. Emotionally, they typically are repressors, denying problems.
  • Idiopathic insomnia
    • Insomnia is long-standing, typically beginning in early childhood.
    • Patients often present with other hard-to-localize neurologic signs and symptoms such as difficulties with attention or concentration, hyperactivity, and mild nonfocal electroencephalographic abnormalities.
    • Emotionally, persons with childhood-onset insomnia are often repressors, denying and minimizing emotional problems.
    • These individuals often show atypical reactions, such as hypersensitivity or insensitivity, to medications.
    • Insomnia tends to persist over the entire life span and can be aggravated by stress or tension.
  • Sleep state misperception: Patients report insomnia subjectively, while sleep duration and quality are completely normal.

Physical

No obvious physical findings are present other than possible signs of sleep deprivation and fatigue such as eye redness.

  • Mental status; drowsiness; and mood changes such as irritability, anxiety, and sad feelings from underlying depression may be noted. The clinician should also note the patient's orientation, memory, judgment, insight, and the presence of any hallucinations or delusions.
  • As with any mental status (but especially with the concern about depression), assess the patient's suicide potential. For completeness, assess the patient's homicidal potential as well.

Causes

Exclusion of other common causes is required to make the diagnosis of primary insomnia.

  • Medical causes
    • Chronic pain, especially neuropathic pain
    • Primary sleep disorders (eg, sleep apnea, periodic limb movements, restless legs syndrome)
    • Dyspnea from any cause
    • Pregnancy
    • Drug use or withdrawal (eg, selective serotonin reuptake inhibitors, stimulants, antihistamines, caffeine, diet pills, herbal preparations containing ma huang, anticonvulsants, steroids)
  • Psychiatric and/or psychological causes
    • Mood disorders (eg, depression, mania): Recent findings have strengthened the evidence that primary insomnia may be linked with mood disorders and is associated with hypothalamic-pituitary-adrenal (HPA) axis overactivity and excess secretion of corticotropin-releasing factor (CRF), adrenocorticotropin-releasing hormone, and cortisol.
    • Anxiety disorders (eg, generalized anxiety, panic attacks, obsessive–compulsive disorder)
    • Substance abuse (eg, alcohol or sedative/hypnotic withdrawal)
    • Major life stressors and/or events
  • Environmental causes
    • Noise
    • Jet lag or shift work
    • Bedroom too hot or cold



Adjustment Disorders
Alcohol-Related Psychosis
Amphetamine Abuse
Anxiety Disorders
Apnea, Sleep
Bipolar Affective Disorder
Caffeine-Related Psychiatric Disorders
Cocaine-Related Psychiatric Disorders
Depression
Hyperthyroidism
Major Depression
Obstructive Sleep Apnea-Hypopnea Syndrome
Parasomnias
Postpartum Depression
Schizophrenia
Sleep Disorder, Geriatric
Sleep Disorders

Other Problems to be Considered

A number of occult medical, psychiatric, and substance abuse disorders can cause sleep disturbance. Also consider other sleep-related disorders, such as circadian rhythm sleep disorder and parasomnias, in the differential diagnosis. Substance abuse can cause insomnia during the intoxication phase, during the sustained use phase, and during withdrawal.



Lab Studies

  • Laboratory studies essentially are not required for the diagnosis of primary insomnia.
  • Tests required to exclude other causes of insomnia include the following:
    • Thyroid function tests (hyperthyroidism)
    • Blood alcohol levels (alcohol-related psychosis)

Imaging Studies

  • Neuroimaging studies may be helpful if a structural lesion is suspected to cause insomnia.

Other Tests

  • Sleep diary (see Media file 1)
    • This is a questionnaire completed by the patient each morning to describe the previous night's sleep.
    • Data from the sleep diary may help minimize distortions in sleep information recalled in the physician's office.
  • Actigraphy: This is a recently developed technique that makes use of an activity monitor to record activities during sleep and waking. It is useful in the diagnosis of circadian rhythm sleep disorders, sleep state misperception, and other types of primary insomnia. In older adults treated for chronic primary insomnia, the clinical use of actigraphy is still suboptimal in detecting wakefulness.

Procedures

  • Polysomnography: This is not recommended for routine evaluation of insomnia but may be used in special circumstances (eg, exclusion of primary sleep disorders).
  • Multiple sleep latency test
    • Psychophysiological insomnia and idiopathic insomnia manifest as increased sleep latency, reduced sleep efficiency, and increased number and duration of awakenings.
    • Sleep state misperception manifests as normal sleep latency (15-20 min), normal number of arousals and awakenings, and normal sleep duration (6.5 h). The multiple sleep latency test shows normal daytime vigilance. Sleep state misperception can be diagnosed only in the laboratory because of the need to document that sleep duration and quality are normal when a person claims to have poor sleep.



Medical Care

Pharmacologic treatment usually provides rapid symptom relief, but controlled studies of long-term treatment have not been conducted.

  • Nonprescription drugs
    • The active agent in many of these over-the-counter medications is one of the sedating antihistamines. They are generally safe but have anticholinergic adverse effects such as dry mouth, blurred vision, urinary retention, and confusion in older patients, which can be potentially more serious in patients with dental caries, glaucoma, prostatic enlargement, and dementia (or delirium), respectively.
    • They are also minimally effective in inducing sleep and may reduce sleep quality. Consequently, discourage patients from using them on a routine basis.
    • Discourage the use of various herbal preparations (eg, herbal tea) and so-called nutritional substances because of the lack of evidence in their support.
    • Studies have shown that melatonin may be useful for short-term adaptation to jet lag or other circadian rhythm sleep disorders. A recent study showed that ramelteon, a highly selective agonist for melatonin subtypes 1 and 2 receptors, is a good option for the treatment of insomnia characterized by difficulty falling asleep. In patients with insomnia, treatment with ramelteon was generally well tolerated and resulted in modest but statistically significant decreases in the latent period for sleep.1 Ramelteon is the first FDA-approved melatonin receptor agonist drug.
  • Prescription drugs
    • Hypnotics and benzodiazepines (BZDs) are the mainstays of short-term treatment of primary insomnia.
    • Basic principles for rational treatment of insomnia are to use the lowest effective dose, to use intermittent dosing (2-3 nights per wk), to use for short term (2-3 wk at a time), to discontinue after slow taper if the patient has been taking it regularly, and to use agents with short and/or intermediate half-life to minimize daytime sedation.
    • Pharmacokinetic properties and risk-benefit ratio are the key factors in selecting the most appropriate medication.

      Table. Commonly Used Hypnotics

      DurationAgentDoseHalf-LifePeak Action
      Long actingFlurazepam15-30 mg48-120 h0.5-1 h
      Quazepam7.5-15 mg41 h2 h
      Intermediate actingEstazolam1-2 mg10-24 h2 h
      Temazepam7.5-30 mg3.5-18 h1.2-1.6 h
      Lorazepam0.5-2 g10-20 h2-4 h
      Oxazepam10-15 mg5-20 h3 h
      Short actingTriazolam0.125-0.5 mg1.5-5.5 h1-2 h
      Zolpidem*5-10 mg2.5 h1.6 h
      Zaleplon†5-10 mg0.9-1 h0.9-1.5 h
      *Zolpidem (Ambien) is in the class of imidazopyridines, structurally unrelated to BZDs.
      †Zaleplon (Sonata) is in the class of pyrazolopyrimidines, also structurally unrelated to BZD.
    • Common adverse effects of hypnotics are as follows:
      • Anterograde amnesia and withdrawal effects may occur, especially with short-acting BZD (not with zolpidem and zaleplon).
      • Residual daytime sedation with intermediate-acting and long-acting drugs may occur, depending on dosage and half-life.
      • Rebound insomnia may occur with short-acting and intermediate-acting BZD after discontinuation.
      • Dosage, pharmacokinetic properties, and risk-benefit ratio are the key factors in selecting the most appropriate medication.
      • Short-acting agents are recommended for patients with difficulty falling asleep, while intermediate-acting drugs are indicated for problems with sleep maintenance.
      • Avoid long-acting agents, especially in older people, because they cause daytime sedation, impair cognition, and thereby increase the risk of falls.
    • Contraindications of these agents are as follows:
      • Pregnancy is a contraindication.
      • Untreated obstructive sleep apnea is a contraindication.
      • History of substance abuse is a contraindication.
      • Caution and close monitoring is needed in older people and in patients with hepatic, renal, or pulmonary disease.
    • Antidepressants are indicated for use in patients with insomnia associated with psychiatric disorders or patients who have a previous history of substance abuse. Sedating antidepressants, such as trazodone and nefazodone, are sometimes used at bedtime in small doses (50 mg). They are not associated with tolerance or withdrawal and do not have anticholinergic adverse effects. SSRIs like paroxetine are found to be ineffective for treating primary insomnia in old age. Like other antidepressants, little scientific evidence supports their efficacy in the treatment of insomnia without associated depression.
  • Nonpharmacologic treatment: Psychological treatment for insomnia consists primarily of patient education and short-term cognitive-behavioral therapies. The focus is primarily on sleep hygiene or factors presumed to perpetuate insomnia; as such, these therapies seek to modify maladaptive sleep habits and to educate patients about healthier sleep practices.
    • Stimulus control therapy: The purpose is to reestablish the connection between the bed and sleep by prohibiting the patient from engaging in nonsleep activities while in bed. The instructions given to the patient are (1) to go to bed only when sleepy, (2) to use the bed and bedroom only for sleep and intimacy, (3) to avoid trying to force sleep (go into another room whenever unable to fall asleep within 20-30 min and return to bed only when sleepy again), (4) to get up at the same time each morning regardless of how much the patient slept the previous night, and (5) to avoid daytime napping.
    • Sleep restriction therapy: This involves limiting the amount of time the patient spends in bed to the actual amount of time the patient usually spends sleeping. This results in sleep deprivation, which accumulates and causes more rapid sleep onset on subsequent nights. As sleep improves, the patient is allowed to gradually increase time in bed by 15-30 minutes.
    • Relaxation therapies: Relaxation-based interventions are indicated based on the observation that patients with insomnia often display high levels of arousal (physiologic and cognitive) both at night and during the daytime. The various techniques available to deactivate the arousal system are (1) progressive muscle relaxation, (2) biofeedback, and (3) imagery training and thought stopping.
    • Cognitive behavior therapy: This consists of identifying patient-specific dysfunctional sleep cognitions, challenging their validity, and replacing them with more adaptive substitutes such as reattribution training, reappraisal, and attention shifting. A recent randomized clinical trial determined that 4 individual, biweekly sessions represent the optimal dosing for cognitive behavioral intervention.2
    • Paradoxical intention: This method consists of persuading a patient to engage in his or her most feared behavior (ie, staying awake). This serves to eliminate performance anxiety so that sleep may come more easily.

Consultations

Consultation with a sleep disorders specialist may be necessary if the standard pharmacologic and behavioral treatments are not effective.



The goals of pharmacotherapy are to reduce morbidity and to prevent complications. In addition to the FDA-approved drugs listed below, new experimental drugs are being developed. Among them is indiplon, which is a unique nonbenzodiazepine experimental drug that acts on a specific site of the gamma-aminobutyric acid (GABA)-A receptor. Initial studies have shown significantly improved subjective measures of sleep induction and maintenance in elderly women with chronic insomnia at a dose of 5-10 mg.3 Gaboxadol is another experimental drug that is a direct-acting GABA-A agonist. It has now entered phase III development for the treatment of insomnia following promising results from phase II trials. An initial trial showed improvement in sleep maintenance and total sleep time.4

Drug Category: Benzodiazepine hypnotics

The primary indication is for short-term management of insomnia, either as the sole treatment modality or as adjunctive therapy until the underlying problem is controlled. Hypnotics can be useful in psychophysiological insomnia for particularly poor nights or when the subjects know ahead of time that they will encounter difficulty sleeping (eg, before an examination or a presentation). An occasional hypnotic can be used for sleep state misperception when the patient becomes extremely worried about perceived lack of sleep for several nights.

Drug NameFlurazepam (Dalmane)
DescriptionLong-acting BZD that acts through GABA receptor. Half-life is 48-120 h, and peak action is 0.5-1 h.
Adult Dose15-30 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; untreated obstructive sleep apnea; history of substance abuse; narrow-angle glaucoma; preexisting CNS depression; respiratory depression
InteractionsIncreased toxicity of BZDs in CNS with coadministration of phenothiazines, barbiturates, and alcohol
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution and close monitoring needed in low albumin levels and hepatic, renal, or pulmonary disease
Causes residual daytime sedation, impaired cognition, and increased risk of falls, especially in older people; caution with other CNS depressants

Drug NameQuazepam (Doral)
DescriptionLong-acting BZD that acts through BZD receptor. Half-life is 41 h, and peak action is 2 h.
Adult Dose7.5-15 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse
InteractionsIncreased toxicity of BZDs in CNS with coadministration of phenothiazines, barbiturates, and alcohol
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution and close monitoring needed in low albumin levels and hepatic, renal, or pulmonary disease
Causes residual daytime sedation, impaired cognition, and increased risk of falls, especially in older people; caution with other CNS depressants

Drug NameEstazolam (ProSom)
DescriptionIntermediate-acting BZD good for sleep maintenance. Half-life is 10-24 h, and peak action is 2 h.
Adult Dose1-2 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse
InteractionsIncreased toxicity of BZDs in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution and close monitoring needed in low albumin levels and hepatic, renal, or pulmonary disease
Causes residual daytime sedation, impaired cognition, and increased risk of falls, especially in older people; caution with other CNS depressants; residual daytime sedation and rebound insomnia after discontinuation is common

Drug NameTemazepam (Restoril)
DescriptionIntermediate-acting BZD good for sleep maintenance. Half-life is 3.5-18 h, and peak action is 1.2-1.6 h.
Adult Dose7.5-30 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse; severe uncontrolled pain
InteractionsIncreased toxicity of BZDs in CNS with coadministration of phenothiazines, barbiturates, and alcohol
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution and close monitoring needed in low albumin levels and hepatic, renal, or pulmonary disease
Causes residual daytime sedation, impaired cognition, and increased risk of falls, especially in older people; caution with other CNS depressants

Drug NameLorazepam (Ativan)
DescriptionIntermediate-acting BZD good for sleep maintenance. Usually used as an anxiolytic. Half-life is 10-20 h, and peak action is 2-4 h.
Adult Dose0.5-2 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
InteractionsToxicity of BZDs in CNS increases when used concurrently with alcohol, phenothiazines, and barbiturates
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease

Drug NameOxazepam (Serax)
DescriptionIntermediate-acting BZD good for sleep maintenance. Usually used as an anxiolytic. Half-life is 5-20 h, and peak action is 3 h.
Adult Dose10-15 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse; severe uncontrolled pain
InteractionsIncreased toxicity of BZDs in CNS with coadministration of phenothiazines, barbiturates, and alcohol
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution and close monitoring needed in low albumin levels and hepatic, renal, or pulmonary disease
Causes residual daytime sedation, impaired cognition, and increased risk of falls, especially in older people; caution with other CNS depressants

Drug NameTriazolam (Halcion)
DescriptionShort-acting BZD recommended for people with difficulty falling asleep. Half-life is 1.5-5.5 h, and peak action is 1-2 h.
Adult Dose0.125-0.25 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse
InteractionsIncreases toxicity of BZDs in CNS with coadministration of phenothiazines, barbiturates, and alcohol
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution and close monitoring needed in low albumin levels and hepatic, renal, or pulmonary disease
Causes residual daytime sedation, impaired cognition, and increased risk of falls, especially in older people; caution with other CNS depressants; rebound insomnia may occur after discontinuation; as a short-acting BZD, can cause amnesia if used in higher than recommended doses

Drug Category: Nonbenzodiazepine hypnotics

These agents are gaining popularity because they do not have significant effect on sleep architecture and are not associated with the rebound phenomenon seen with the benzodiazepines.

Drug NameZolpidem (Ambien, Ambien CR)
DescriptionThis is in the class of imidazopyridines, structurally unrelated to BZDs. Recommended for people with difficulty falling asleep. Half-life is 2.5 h, and peak action is 1.6 h.
The extended-release product (Ambien CR) consists of a coated two-layer tablet and is useful for treating insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The first layer releases drug content immediately to induce sleep, whereas the second layer gradually releases additional drug content to provide continuous sleep.
Adult Dose5-10 mg PO hs prn
Extended-release: 12.5 mg PO hs
Extended-release in elderly patients: 6.25 mg PO hs
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; lactation; untreated obstructive sleep apnea; history of substance abuse
InteractionsIncreases toxicity of alcohol and CNS depressants; effect may be delayed if taken with food or shortly after a meal
PregnancyX - Contraindicated in pregnancy
PrecautionsMonitor elderly patients for impaired cognitive or motor performance; caution in hepatic, renal, or pulmonary disease; visual hallucinations are associated with rapid withdrawal and restarting of zolpidem; use of lowest effective dose may prevent hallucinations; extended-release dosage form must be swallowed whole (do not divide, chew, or crush)

Drug NameZaleplon (Sonata)
DescriptionImidazopyridine, structurally unrelated to BZDs. Recommended for people with difficulty falling asleep. Half-life is 0.5-1 h, and peak action is 0.5-1 h.
Adult Dose5-10 mg PO hs prn; in patients with hepatic function impairment, reduce dose to 5 mg PO hs
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; pregnancy; untreated obstructive sleep apnea; history of substance abuse
InteractionsCimetidine significantly increases levels of zaleplon
PregnancyX - Contraindicated in pregnancy
PrecautionsFailure of insomnia to remit after 7-10 d of treatment may indicate need for evaluation of a primary psychiatric or medical illness; limit treatment to 7-10 d and reevaluate patient if zaleplon is to be taken for >2-3 wk (do not prescribe in quantities exceeding a 1-mo supply); in hepatic function impairment, reduce dose to 5 mg PO hs; caution in patients exhibiting signs or symptoms of depression

Drug NameEszopiclone (Lunesta)
DescriptionNonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown but is 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 of 6 h. Higher doses (ie, 2 mg for elderly adults and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg for elderly adults and 2 mg for nonelderly adults) are suitable for difficulty in falling asleep.
Adult DoseNonelderly adults: 2 mg PO hs; may increase to 3 mg PO hs prn
Elderly adults: 1 mg PO hs initially; not to exceed 2 mg PO hs
Severe hepatic impairment: Do not exceed 2 mg PO hs
Pediatric Dose<18 years: Not established
>18 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsCYP3A4 and CYP2E1 substrate; potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, nelfinavir) increase AUC, Cmax, and t1/2 and therefore potential toxicity (decrease dose); potent CYP3A4 inducers (eg, rifampicin) increase clearance; coadministration with alcohol or other CNS depressants may increase effect and toxicity (decrease dose); coadministration with olanzapine may decrease DSST scores; sleep onset may be delayed if taken with or immediately after a high-fat or heavy meal
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsMay cause dysgeusia, headache, or coldlike symptoms; rare adverse effects associated with hypnotics include short-term amnesia, confusion, agitation, hallucinations, worsened depression, or suicidal thoughts; high doses (ie, 6-12 mg) produce euphoric effects similar to those of diazepam 20 mg; anxiety, abnormal dreams, nausea, and upset stomach may occur within 48 h after discontinuing; alertness may be affected the following day, use caution while operating machinery or driving a car

Drug Category: Antidepressants

Indicated for use when insomnia is associated with psychiatric disorders or if the patient has a history of substance abuse. As with other antidepressants, little scientific evidence supports efficacy in the treatment of insomnia without associated depression.

Drug NameNefazodone (Serzone)
DescriptionSedating antidepressant; may be used in small dose at bedtime. Not associated with tolerance or withdrawal effects. Does not have anticholinergic adverse effects.
Adult Dose50-100 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; MAOIs within 14 d of initiating treatment
InteractionsIncreases effects of digoxin, carbamazepine, triazolam, alprazolam, and protease inhibitors through its effect of inhibiting CYP3A4 enzyme; serotonin syndrome may occur when used with other serotonergic agents such as buspirone, meperidine, tramadol, dextromethorphan, triptans, mirtazapine, SSRIs, and especially with MAOIs
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsCaution in cardiac disease, cerebrovascular disease, or seizures

Drug NameTrazodone (Desyrel)
DescriptionSedating antidepressant that may be used in small dose at bedtime. Not associated with tolerance or withdrawal effects. Does not have anticholinergic adverse effects.
Adult Dose50-100 mg PO hs prn
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsCimetidine significantly increases levels of trazodone; serotonin syndrome may occur when used with other serotonergic agents such as buspirone, meperidine, tramadol, dextromethorphan, triptans, mirtazapine, nefazodone, SSRIs, and especially with MAOIs
PregnancyX - Contraindicated in pregnancy
PrecautionsHypotension has occurred, including orthostatic hypotension and syncope; may produce drowsiness, dizziness, or blurred vision; patients taking this medication should be cautious while driving or performing other tasks requiring alertness, coordination, or dexterity; caution in cardiac disease, cerebrovascular disease, or seizures; discontinue therapy and reevaluate if priapism occurs

Drug Category: Melatonin agonists

Indicated for insomnia characterized by difficulty with sleep onset.

Drug NameRamelteon (Rozerem)
DescriptionMelatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep thought to be involved in maintenance of circadian rhythm and normal sleep-wake cycle.
Adult Dose8 mg PO 30 min before bedtime on empty stomach
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; strong cytochrome P450 CYP1A2 inhibitors (eg, fluvoxamine); severe hepatic impairment
InteractionsMajor substrate of cytochrome P450 CYP1A2 and minor substrate of CYP2C and CYP3A4; strong CYP1A2 inhibitors (eg, fluvoxamine) increase AUC up to 190-fold and Cmax 70-fold; strong CYP inducers (eg, rifampin) decrease total exposure by mean of 80%; strong CYP3A4 inhibitors (eg, ketoconazole) and strong CYP2C9 inhibitors (eg, fluconazole) may increase serum levels
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsCaution with mild hepatic impairment; adverse effects leading to discontinuation in clinical trials included dizziness, nausea, fatigue, headache, and worsening insomnia



Further Inpatient Care

Inpatient care is not usually required unless significant medical or psychiatric comorbidity exists.

Further Outpatient Care

Effective treatment for insomnia consists of a dual approach using nonpharmacologic techniques and appropriate use of hypnotic agents.

Deterrence/Prevention

Proper attention to sleep hygiene may prevent the development of psychophysiological insomnia.

Complications

Sleep disturbance is a reliable indicator of psychological ill health, physical ill health, or both. A report of disturbed sleep from the patient signals the need for further evaluation and close monitoring.

Prognosis

In some patients, improvement in sleep leads to an improved quality of life.

Patient Education



Medical/Legal Pitfalls

  • Failure to diagnose



Media file 1:  Primary insomnia. Evaluation of insomnia. Format of sleep diary.
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Article Last Updated: Feb 4, 2008