Approximately 30% of the U.S. population reports experiencing insomnia, with 5% to 15% of the total population meeting the formal criteria for chronic insomnia.^1–3 The American Academy of Sleep Medicine defines insomnia as impairment of the initiation, duration, consolidation, or quality of sleep that occurs despite adequate opportunity for sleep and results in some form of daytime impairment.⁴ Chronic insomnia is diagnosed when patients have symptoms at least three times a week for three months or longer.^4,5 Insomnia can have a significant impact on a patient's quality of life, leading to decreased productivity, increased fatigue and drowsiness, and higher risk of developing other health problems.^6,7

Numerous medical disorders are associated with chronic insomnia, including, but not limited to, hypertension, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, benign prostatic hyperplasia, chronic pain, gastroesophageal reflux disease, depression, anxiety, post-traumatic stress disorder, and substance use disorders (e.g., caffeine, alcohol, stimulants, opioids).^8,9 To successfully treat chronic insomnia, the care team must address any underlying conditions that may be contributing.

Evaluation and Initial Treatment

A comprehensive evaluation of the patient should include a thorough medical and psychiatric history, a detailed assessment of sleep-related behaviors and symptoms, a physical examination, and laboratory testing as needed. The sleep assessment should include the patient's sleep hygiene regimen. Sleep hygiene practices, such as maintaining a regular sleep schedule, reducing exposure to screens before bedtime, creating a quiet and dark sleep environment, and using the bedroom only for sleep and intercourse, should be implemented. Cognitive behavior therapy for insomnia (CBT-I) is the first-line treatment for chronic insomnia (Figure 1).¹⁰ [corrected] When nonpharmacologic approaches are ineffective, medications may be considered in the short term (i.e., less than three months), but they should not be used for long-term treatment of insomnia.

Nonpharmacologic Therapies

COGNITIVE BEHAVIOR THERAPY FOR INSOMNIA

CBT-I focuses on changing negative thought patterns and behaviors that contribute to insomnia. It consists of five elements: cognitive restructuring, stimulus control, sleep hygiene, relaxation therapy, and sleep restriction.^11,12 Each element can be used individually, but treatment is most effective when all five components are used together. CBT-I has been shown to increase stage N2 (i.e., light sleep, no rapid eye movement [REM]), stage N3 (i.e., deep sleep, no REM), and REM sleep, while decreasing wakefulness and stage N1 sleep (i.e., the first one to seven minutes after a patient first falls asleep), which improves overall sleep architecture.^3,13 CBT-I is particularly helpful for patients with chronic insomnia and comorbid medical conditions, such as chronic pain, depression, posttraumatic stress disorder, cancer, and chronic obstructive pulmonary disease.^14–16 Clinicians with experience in CBT-I can be found through professional organizations such as the Society of Behavioral Sleep Medicine and the American Board of Sleep Medicine.

Through cognitive restructuring, CBT-I addresses maladaptive beliefs and expectations that patients may have to reduce anxiety about inadequate sleep and its consequences. Physicians should set expectations with patients for total sleep duration (5 to 6 hours per night, on average) and focus on supporting daytime function.¹⁷

Stimulus control reduces stimuli that increase wakefulness before and during sleep time. Patients should associate their beds with only sleep and intercourse, avoid exposure to screens before bedtime, and get out of bed if they are having trouble sleeping.⁸

Sleep hygiene is improved by avoiding naps, caffeine, and alcohol before bedtime and maintaining a stable sleep schedule.⁸ The evidence for sleep hygiene alone is weak; the American Academy of Sleep Medicine recommends that the other components of CBT-I be used at the same time.⁶

Relaxation therapy improves self-reported sleep quality, sleep latency, and beliefs and attitudes about sleep.¹¹ Relaxation techniques, including progressive muscle relaxation, abdominal breathing, mindfulness, and meditation, reduce mental activity and physical tension before bed.⁸

Sleep restriction is the most effective component of CBT-I. It improves self-reported sleep quality and insomnia severity and reduces the frequency of awakenings.¹¹ This component increases the drive to sleep by limiting the time allowed for sleep, inducing sleep debt to improve the proportion of time in bed spent asleep and consolidate fragmented sleep. Physicians should ask patients to keep a sleep diary for one to two weeks, then set a consistent wake-up time for getting out of bed with a consistent total time spent in bed. This duration is calculated as the usual total sleep time as perceived by the patient plus 30 minutes, but it must be less than six hours. Sleep restriction is not appropriate for patients with comorbid medical conditions that worsen with sleep deprivation, such as bipolar disorder, seizure disorder, or untreated sleep disorders (e.g., obstructive sleep apnea).¹⁷

Although evidence is lacking, the American Academy of Sleep Medicine suggests that physicians consider using single components of CBT-I, particularly sleep restriction, for the treatment of chronic insomnia.⁶

OTHER NONPHARMACOLOGIC THERAPIES

Brief therapies for insomnia typically include education about behaviors that improve or interfere with sleep, relaxation techniques, and sleep restriction.^8,18 Brief therapies improve self-reported sleep quality and insomnia severity.¹¹

Exercise improves self-reported sleep quality in younger and older adults and may improve sleep efficiency. For patients older than 65 years, muscle endurance training combined with walking is the best type of exercise to improve sleep quality.^19,20

Mindfulness meditation emphasizes awareness and attention to the present to promote mind and body calmness and relaxation. Mindfulness-based stress reduction teaches meditation through a structured group intervention and mindfulness-based therapy for insomnia. It improves self-reported sleep quality and decreases insomnia severity.^6,11 Mindfulness-based stress reduction is most useful in combination with CBT-I.^21,22

Meditative movements such as yoga and tai chi may be helpful in improving sleep quality, but data to support these techniques are limited, and results have been mixed.²³

Verum acupuncture may improve total sleep time, sleep efficiency, nighttime awakenings, and self-reported sleep quality.²⁴ The evidence supporting acupuncture is limited to verum or traditional acupuncture and requires 12 or more treatments.

Pharmacologic Treatments

When nonpharmacologic approaches are ineffective, medications may be considered. In patients with chronic insomnia, medications may be used alone or in combination with CBT-I, but long-term use (i.e., more than three months) is discouraged.²⁵ Several common classes of medications are used to treat insomnia (Table 1).¹⁰

SEDATIVE-HYPNOTIC MEDICATIONS

Benzodiazepines are gamma-aminobutyric acid (GABA) receptor agonists that bind to GABA receptors in neurons, leading to decreased neuronal excitability and causing sedation, decreased anxiety, and muscle relaxation.²⁶ Five benzodiazepines have been approved by the U.S. Food and Drug Administration (FDA) for treatment of insomnia: temazepam, triazolam, quazepam, flurazepam, and estazolam.²⁶ Benzodiazepines are associated with a risk of dependence and have significant adverse effects including daytime sedation, ataxia, falls, cognitive impairment, respiratory depression, rebound insomnia, and anterograde amnesia.^4,27,28

Z-DRUGS

Nonbenzodiazepine hypnotics are known as the Z-drugs and include zaleplon, zolpidem, and eszopiclone (Lunesta). They are the most prescribed medications for treatment of insomnia. Like benzodiazepines, they bind to GABA receptors, causing hyperpolarization of neuron cells; however, they bind more selectively to subunits on the GABA receptor, targeting the sedative effects of the receptor instead of causing the anxiolytic effect.²⁹ The Z-drugs are associated with motor vehicle crashes, falls, and fractures.²⁸ Complex sleep-related behaviors such as sleepwalking and sleep eating can happen and are more likely to occur in patients with a history of sleepwalking. Physicians should prescribe these medications at the lowest dose possible and instruct patients to take the medication close to bedtime. They should not be used in combination with other sedative medications.²⁹ Of the GABA receptor agonists, eszopiclone has the best evidence for effectiveness in long-term use.²⁷

ANTIEPILEPTICS

Gabapentin and pregabalin (Lyrica) are prescribed off-label for insomnia. There is limited evidence to recommend this use, but gabapentin may be useful for patients with insomnia and restless legs syndrome. Adverse effects include daytime sedation, weight gain, and dizziness.³⁰

MELATONIN RECEPTOR AGONISTS

Melatonin receptor agonists work by binding to and activating melatonin receptors in the brain, helping to regulate the sleep-wake cycle. Melatonin receptor agonists have a low risk of dependence or abuse and are generally well tolerated.³⁰ The FDA has approved use of two melatonin receptor agonists: ramelteon (Rozerem) and tasimelteon (Hetlioz).³¹ Tasimelteon is FDA approved only for non–24-hour sleep-wake disorder and is extremely expensive. The most common adverse effect is rare daytime sedation. Ramelteon has been shown to have small to moderate benefits for sleep latency but no significant improvement in total sleep time or wake time after sleep onset.

Over-the-counter melatonin products are not regulated by the FDA, and purity varies widely among products.³² A meta-analysis showed a small benefit for sleep latency and total sleep time.

Melatonin may be considered a first-line pharmacologic agent for sleep onset in older adults, including hospitalized patients and those in long-term care facilities, starting with a dosage of 0.5 mg per day.^8,33

DUAL OREXIN RECEPTOR ANTAGONISTS

Orexins are neuropeptides that bind to orexinergic neurons, promoting arousal in areas of the brain. Dual orexin receptor antagonists reversibly bind to orexin receptors, which inhibits activation of the arousal system.³⁴ This class of medications is effective in patients who have sleep maintenance insomnia or difficulty with sleep onset. The FDA has approved the use of daridorexant (Quviviq), lemborexant (Dayvigo), and suvorexant (Belsomra). A 2020 meta-analysis comparing lemborexant to suvorexant found that both drugs were more effective than placebo for primary sleep measures such as sleep latency and increased total sleep time, but the effect of lemborexant was greater than that of suvorexant.³⁵ Lemborexant also has the strongest evidence for effectiveness when used for more than four weeks.²⁵ The most common adverse effect is daytime sedation.³⁶

ANTIDEPRESSANTS/ANTIHISTAMINES

Doxepin is a tricyclic antidepressant that functions as a histamine receptor antagonist, enhancing sleep maintenance (i.e., time awake after sleep onset and total sleep time). Doxepin is FDA approved at dosages of 3 to 6 mg per day.³⁵ Several antidepressants are used off-label for the treatment of insomnia, such as trazodone, mirtazapine, amitriptyline, and nortriptyline. Trazodone is not recommended due to a lack of clinically significant benefits. Due to limited evidence, other antidepressants should be considered only if there is another indication to treat a comorbid mental health condition.²⁵

Although antihistamines (e.g., diphenhydramine, doxylamine) are FDA approved for insomnia, evidence for effectiveness is generally lacking, except for doxylamine, which is effective for use up to four weeks.²⁵

ANTIPSYCHOTICS

Several antipsychotics (olanzapine [Zyprexa], quetiapine, and risperidone) are used off-label for the treatment of insomnia, but the evidence for their use is weak. These medications should be used only if the patient has another indication for treatment of a co-occurring medical condition.³²

SAFETY CONSIDERATIONS

Benzodiazepines, Z-drugs, and dual orexin receptor antagonists are classified as schedule IV drugs by the U.S. Drug Enforcement Administration. Patients taking these medications should be monitored with periodic urine drug screens to test for drugs of abuse. Additionally, prescription drug monitoring systems should be used to track prescriptions of controlled substances.

This article updates a previous article on this topic by Matheson and Hainer¹⁰ and other articles by Maness and Khan,³⁷ Harsora and Kessmann,³⁸ Ramakrishnan and Scheid,³⁹ Rajput and Bromley,⁴⁰ and Eddy and Walbroehl.⁴¹

Editor's Note: AFP has a strict policy on conflicts of interest, and the editing team is diligent about obtaining and investigating disclosures prior to acceptance as well as investigating any new disclosures that arise between acceptance and publication. To guard against untoward influence and intentional or unintentional bias in our clinical review articles, we rarely choose to work with authors who have relevant industry ties, even though mitigation strategies such as disclosure and peer review could be used to allow this practice. We publish disclosures for all AFP authors, and all clinical review articles are peer-reviewed. More about our long-standing policies can be found in the editorial, AFP's Conflict of Interest Policy: Disclosure Is Not Enough. We publish this disclosure of Dr. Matheson’s for full transparency and to point out that had he been an active researcher for a drug company that made a drug discussed in his article, his article would not have been published in AFP.

Data Sources: A search was completed in Essential Evidence Plus, the Cochrane database, and PubMed using the keywords chronic insomnia, cognitive behavioral therapy for insomnia, sleep hygiene, stimulus control, exercise and sleep, relaxation and insomnia, acupuncture and insomnia, sedatives and insomnia, hypnotics and insomnia, antihistamines and insomnia, orexin inhibitors, antidepressants, and insomnia. The search included meta-analyses, randomized controlled trials, and systematic reviews. The Centers for Disease Control and Prevention sources were reviewed for epidemiology data. Search dates: January, February, and March 2023.