Introduction   Fast Fact #101 and Fast Fact #104 reviewed assessment of insomnia and its non-pharmacological therapy.  This Fast Fact focuses on the pharmacological treatment of insomnia.  Prior to pharmacological treatment, it is important to improve sleep hygiene and treat any contributing underlying medical conditions (e.g. depression, pain, worsening CHF or COPD). 

Non-Specific Drug Treatment:

Benzodiazepines (BZDs) are commonly prescribed to improve sleep quality, total sleep time, and reduce night-time awakenings in the short term (weeks to a few months). However, there are concerns about their use long term and in the cognitively frail. BZDs are dosed orally, at bedtime for insomnia. It is best to select BZDs with longer half-lives such as temazepam (start 7.5 mg, FDA approved for insomnia), clonazepam (0.5 mg), triazolam (0.125 mg), and flurazepam (15 mg) for insomnia. Most BZDs (except temazepam) undergo hepatic metabolism via cytochrome P450 system and can have numerous drug-drug interactions. BZDs have a high incidence of amnesia and rebound insomnia, particularly in anxious patients, and may be associated with paradoxical agitation, falls, hip fractures, and cognitive impairment, especially in the elderly. Tolerance and dependence occur with long-term use. Additive risks for CNS and respiratory depression, delirium, and falls occur when co-prescribed with opioids. 

Benzodiazepine receptor agonists: like BZDs, these medications modulate GABA-A receptors to induce CNS depression.  Unlike BZDs, they have less drug interactions, lower abuse potential, and less rebound insomnia upon abrupt discontinuation. Zolpidem (5-10 mg) and zaleplon (10-20 mg), are shorter acting agents in this class (half-life 1-2 hours), while eszopiclone (1-2 mg) has a half-life of 6-9 hours.  Zolpidem is also available in a controlled-release formulation. There is growing concern for cognitive decline when used beyond a few months and about an association with nocturnal behaviors including sleepwalking and sleep-driving.  

Antidepressants such as trazodone (25-100 mg), doxepin (3-6 mg), and mirtazapine (5-15 mg) are commonly used for insomnia due to their sedative properties. Of these medications, mirtazapine likely has the strongest supporting evidence. Trazodone has recently been associated with fall-related injuries in patients who reside in nursing homes. 

Orexin receptor antagonists: See Fast Fact #496 for a more in-depth discussion. Initial studies suggest these medications appear are safe and effective, even for patients with dementia in promoting sleep induction and maintenance; however, most of these studies have been industry sponsored so far.  Examples include suvorexant, lemborexant, and daridoexant. Cost and insurance coverage may limit their use. 

Atypical antipsychotics: most of the atypical antipsychotics (quetiapine, olanzapine and ziprasidone), except for risperidone, improve total sleep time and/or sleep efficiency in healthy subjects and schizophrenic patients. These may be beneficial in patients with insomnia from delirium who do not respond to front-line non-pharmacologic treatments. 

Antihistamines and over-the-counter drugs: Diphenhydramine or other classical antihistamines are generally not preferred in patients older than 65 due to delirium and fall risks from their anticholinergic properties. Of note, many over the counter products for insomnia contain diphenhydramine or a similar sedating antihistamine, including Unisom, Tylenol PM, and Nyquil.   

Melatonin is used for circadian rhythm sleep disorders and is less effective for chronic insomnia (see Fast Facts # 306). It has short half-life (45-60 min), has been used in doses ranging from 0.3 to 20 mg. It is not FDA approved, and data are mixed regarding its efficacy. 

Melatonin receptor agonists: Ramelteon (8 mg) is FDA approved for insomnia, has a half-life of 1–2.6 hours. It has been shown to reduce sleep latency and increased total sleep time in patients more than 65 years old with chronic insomnia. Side effects are similar to that of placebo and include headache and sore throat. Its primary advantage is that there is no evidence of abuse and dependence, rebound insomnia, or withdrawal effects. 

Dronabinol: This synthetic-derived, THC derivative may provide a short-term hypnotic effect for weeks to months, but insurance coverage, drug-supply issues, and cost issues limit its use.  Many patients instead pursue non-prescription cannabis products at dispensaries. In general, the higher the THC:CBD ratio for these products, the greater the somnolence effect. 

Herbal remedies: there is conflicting evidence about valerian (oral extract 400-900 mg QHS) as a mild hypnotic. The major side effects are hepatotoxicity, cardiotoxicity and delirium.  

Drugs for specific sleep disorders: See Fast Fact #217 for treatment of restless leg syndrome.   Discussion of therapies for narcolepsy and nocturnal myoclonus or periodic leg movements is beyond the scope of this Fast Fact.    

Miscellaneous sedative hypnotics:  Choral hydrate and barbiturates have moderate short-term efficacy, but they are both more toxic than BZDs and tolerance can build up quickly. Once commonly used for insomnia, these drugs are no longer used except in rare circumstances.

References 

1. Sateia MJ, et al.  Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an AASM clinical practice guideline.  J Clin Sleep Med 2017; 13(2): 307-349.
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3. Schenck CH, Mahowald MW, Sack RL.  Assessment and management of insomnia. JAMA.  2003; 289:2475-2479.
4. Bronskill SE, et al.  Low dose trazodone, benzodiazepines and fall-related injuries in nursing homes: a matched cohort study. JAGS 2018 66(10):1963-1971.
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9. Buscemi N, Vandermeer B, Hooton N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ. 2006; 332(7538):385-93.
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11. Maruani, Julia, et al. Efficacy of melatonin and ramelteon for the acute and long‐term management of insomnia disorder in adults: A systematic review and meta‐analysis. Journal of Sleep Research 32.6 (2023): e13939.
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Author Affiliations:  University of Pittsburgh Medical Center, Pittsburgh, PA.
Version History:  This Fast Fact was originally edited by David E Weissman MD, and published in November 2003.  2nd Edition in April 2009; 3rd Edition in September 2011; 4th Edition in June 2025.
Conflicts of Interests: None to report.