Insomnia is a serious health problem that affects millions of people. Population surveys have estimated the prevalence of insomnia to be about 30% to 50% of the general population. Variation in estimates depends on different methods of surveying and definitions of insomnia.1 About three-fourths of people who have trouble sleeping say that the problem is “occasional,” averaging about 6 nights per month. The other one-fourth have frequent or chronic insomnia, averaging about 16 nights per month.2 Individuals with insomnia most often report a combination of difficulty falling asleep and intermittent wakefulness during sleep.3 The most common symptoms of insomnia are waking up feeling unrefreshed and waking often during the night. The symptoms waking up too early and difficulty falling asleep are less common but still experienced at least a few nights a week by about 25% of adults with insomnia.1 The risk of insomnia increases with age; affecting approximately 20% to 40% of older adults at least a few nights per month.2

Consequences of insomnia can include increased risk of depression, poor memory, reduced concentration, and poor work performance. Insomnia has been associated with poor general health, greater healthcare utilization, lower quality of life, lower socioeconomic status, and poorer social relationships, mood, and cognitive function.4 Insomnia can be acute and transient. It also can be chronic, especially when associated with underlying psychiatric or medical illness.

Treatment of insomnia involves behavioral changes, such as minimizing habits that interfere with sleep (for example, drinking coffee or engaging in stressful activities in the evening),4 and pharmacotherapy with sedating antidepressants (for example, trazodone), sedating antihistamines, anticholinergics, benzodiazepines, or nonbenzodiazepine hypnotics. The benzodiazepines and the newer sedative hypnotics zolpidem, zaleplon, zopiclone, and eszopiclone work through gamma-aminobutyric acidreceptors. Ramelteon, a hypnotic approved by the United States Food and Drug Administration (FDA) in July 2005, is a selective melatonin receptor (MT1 and MT2) agonist. New nonbenzodiazepine drugs have been sought for multiple reasons, including reduction of the risk of tolerance, dependence, and abuse associated with benzodiazepines.

The newer drugs for insomnia differ from each other in their pharmacokinetics (see Table 1), and thus could be expected to affect different aspects of insomnia. For example, drugs with a shorter half-life might be effective for helping a person fall asleep faster but less effective for increasing the total time spent asleep during the night.5

Table 1

Table 1

Newer drugs for insomnia

In general, use of insomnia drugs is recommended to be short-term; however, it is recognized that some individuals may require longer-term treatment.4

Scope and Key Questions

The purpose of this review is to help policy makers and clinicians make informed choices about the use of newer drugs for insomnia. Our goal is to summarize comparative data on efficacy, effectiveness, tolerability, and safety.

The Oregon Evidence-based Practice Center wrote preliminary Key Questions identifying the populations, interventions, and outcomes of interest and, based on these, the eligibility criteria for studies. These Key Questions were reviewed and revised by representatives of organizations participating in the Drug Effectiveness Review Project. The participating organizations of the Drug Effectiveness Review Project are responsible for ensuring that the scope of the review reflects the populations, drugs, and outcome measures of interest to clinicians and patients. The participating organizations approved the following Key Questions to guide this review:

  1. What is the comparative effectiveness of newer drugs for insomnia in treating patients with insomnia?
  2. What are the comparative tolerability and safety of newer drugs for insomnia when used to treat patients with insomnia?
  3. Are there subgroups of patients for which one newer drug for insomnia is more effective or associated with fewer adverse events based on
    1. demographics (age, racial groups, and gender)?
    2. other medications (for example, stimulants)?
    3. co-morbidities (including obstructive sleep apnea and other mental disorders)?
    4. pregnancy?
    5. history of substance abuse?

Included populations

Adults and children with insomnia of any duration, including the following DSM-IV-TR diagnoses:

  • Primary insomnia
  • Breathing-related sleep disorder (for example, obstructive sleep apnea)
  • Insomnia related to another mental disorder
  • Substance-induced sleep disorder, insomnia type
  • Sleep disorder due to a general medical condition, insomnia type

Included interventions

Six nonbenzodiazepine drugs for insomnia have been introduced since 1992 (Table 1). Five are available in the US (eszopiclone, ramelteon, zaleplon, zolpidem, and zolpidem extended release) and two in Canada and other countries (zaleplon and zopiclone).

The recommended starting dose in older adults is half the recommended adult dose for all of these drugs except ramelteon because of the theoretical risk of increased adverse events such as somnolence. This is generally based on increased bioavailability observed in older adults.

Included outcomes

Improvement in insomnia is measured in several ways. Effectiveness outcomes include sleep latency, sleep duration, number of awakenings, sleep quality, daytime alertness, rebound insomnia, and quality of life. Safety outcomes include tolerance, adverse effects, abuse potential, withdrawal symptoms, and dependency.

Sleep latency is the time taken by a person to fall asleep. Sleep duration is the time a person remains asleep. The number of awakenings during the night is often measured in insomnia trials. A measure used in some studies is wake time after sleep onset (WASO). This is the total time that a person is awake between sleep onset and final waking.

These outcomes can be measured subjectively (for example, using patient sleep diaries), or objectively, using polysomnography, the testing of sleep cycles and stages through the use of continuous recordings of brain waves and other measures in a sleep laboratory. Most studies report subjective outcomes. While objective measures may give a more accurate indication of sleep duration and other outcomes, subjective outcomes may be more important to patients.

Sleep quality is usually measured by patient questionnaire using a Likert or visual analog scale (for example, 0=poor to 10=excellent). Similarly, daytime alertness and other next-day effects are usually measured by patient self-report.

Rebound insomnia is worsening of insomnia from baseline (prior to pharmacotherapy) when treatment is discontinued. Rebound insomnia can be determined through any of the outcomes listed earlier.

Quality of life includes influence upon physical, psychological, and social aspects of the patient.