Prior to nonspecific drug treatment, it is important to use and evaluate the results/effects of the nonpharmacological treatments to improve sleep.

- Benzodiazepines. Temazepam, estazolam, triazolam, quazepam, and flurazepam have been successfully used for short-term insomnia as they improve sleep quality and total sleep time, and reduce night-time awakenings. Temazepam and estazolam are medium half-life (10-24 hours); triazolam has a shorter half-life (< 6 hours), quazepam and flurazepam are longer lasting (half-life up to 3-7 days in older persons). All drugs are dosed orally, at bedtime.

Side effects:
- high incidence of amnesia and rebound insomnia
- paradoxical agitation
- increased risk of falls, hip fractures
- cognitive impairment
- tolerance and dependence with long-term use
- additive CNS and respiratory side effects when used with other drugs.

- Benzodiazepine receptor agonists. Zolpidem and zaleplon, both dosed at bedtime, are ultra-short acting agents (half-life 1-2 hours) that restore sleep in patients with nocturnal awakenings. Eszopiclone (1-2 mg) has a half-life of 6-9 hours. These are rapidly absorbed, have low abuse potential, and do not cause rebound insomnia.

- Antidepressants. Trazodone, doxepin, amitriptyline, imipramine, and mirtazapine are frequently used for insomnia due to their sedative properties.

- Atypical antipsychotics. Quetiapine, olanzapine, and ziprasidone improve total sleep time and/or sleep efficiency in healthy subjects and schizophrenic patients. These may be beneficial in patients with insomnia unresponsive to front-line treatment or insomnia in patients with delirium.

- Miscellaneous sedative hypnotics. Choral hydrate (more toxic than benzodiazepines) and barbiturates (rapidly develop tolerance) are no longer used except in rare circumstances.

- Antihistamines and over-the-counter drugs. Diphenhydramine or other classical antihistamines have sedative properties, but they are generally not preferred in the elderly due to anticholinergic properties and drug interactions. Diphenhydramine increases sleep duration but not quality; its half-life is ~5-10 hours, but is much longer in elderly.

- Melatonin is used for circadian rhythm sleep disorders and is less effective for chronic insomnia. It does not have any significant effects on either sleep onset latency or sleep efficiency.

- Melatonin receptor agonists. Ramelteon, tasimelteon, and agomelatine. Ramelteon reduce sleep latency and increase total sleep time in patients more than 65 years old with chronic insomnia; there is no evidence of abuse and dependence, rebound insomnia, or withdrawal effects.

- Herbal remedies. Valerian (oral extract) may be as effective as mild hypnotics; the major side effects are hepatotoxicity, cardiotoxicity and delirium.

See reference for more information.

Adapted from Arnold R, Miller M, Mehta R. Insomnia: pharmacologic treatments. Palliative Care Network of Wisconsin. Fast facts and concepts #105. Internet. Available at https://www.mypcnow.org/fast-fact/insomnia-drug-therapies/. Accessed on June 20, 2021