Sleep problems affect up to 50% of older adults. When left untreated, they can contribute to falls, cognitive decline, depression, and even increased frailty and mortality. While hypnotics are commonly prescribed to address these issues, these medications often bring their own risks of falls, hip fractures, and delirium, hence their classification as “potentially inappropriate medications” within the Beers Criteria (American Geriatrics Society, J Am Geriatr Soc 2023;71(7):2052–2081). This article examines the potential adverse effects of various sleep agents in the geriatric population.

Your first step should always be to identify and address underlying causes of insomnia. Medications such as beta-blockers, corticosteroids, nonsteroidal anti-inflammatory drugs, decongestants, antiandrogens, diuretics, bupropion, and levodopa can contribute to sleep issues (Patel D et al, J Clin Sleep Med 2018;14(06):1017–1024). Patients may also use herbal remedies like valerian or chamomile—always ask about these due to potential drug interactions. Once you’ve ruled out or managed these factors, start with nonpharmacologic interventions such as cognitive behavioral therapy for insomnia (see article “Prescribing Medications for Sleep Disorders in Older Adults” on page 1). If medication is necessary, comorbid conditions, polypharmacy, and age-related pharmacokinetic and pharmacodynamic changes become significant concerns. Choose the safest option at the lowest effective dose.

Medications: What to watch for
When pharmacologic treatment is necessary, choosing the right medication requires a careful balance between effectiveness and safety. Below, we review commonly used sleep medications, arranged by frequency of use in clinical practice.

Benzodiazepines (BZDs) and Z-drugs
BZDs and Z-drugs have long been used to treat insomnia but are now considered potentially inappropriate for older adults. They are called out within the Beers Criteria due to risks including cognitive impairment, delirium, syncope, unsteady gait, and falls. These agents may also rarely lead to complex sleep-related behaviors like sleepwalking and sleep driving.

When used with other central nervous system depressants (eg, opioids), BZDs and Z-drugs can exacerbate sedation and increase the risk of respiratory depression (American Geriatrics Society, 2023). Longer-acting agents (eg, flurazepam, eszopiclone, zolpidem controlled release) are particularly problematic, often causing next-day drowsiness and confusion. 

Shorter-acting options (eg, zaleplon) may have a slightly better safety profile but still carry risks. Among BZDs, lorazepam is sometimes preferred in older adults due to its lack of active metabolites, but it too should be used cautiously.

Discontinuing chronic BZD use requires a slow taper to avoid withdrawal symptoms.

Antidepressants
Although none of the antidepressants can mimic normal sleep architecture, some of them may offer dual benefits for patients with psychiatric comorbidities and insomnia:

Trazodone: frequently used to improve sleep onset and maintenance due to its sedating properties. Monitor for orthostasis, next-morning grogginess, dry mouth, blurred vision, falls, and rare cases of priapism.

Mirtazapine: promotes sleep through its antihistaminergic properties; effective in improving sleep continuity but may cause weight gain and increased appetite. 

Doxepin: FDA approved at low doses (3–6 mg) for insomnia; is effective in reducing wakefulness after sleep onset and increasing total sleep time. Avoid it in patients with untreated narrow-angle glaucoma or severe urinary retention.

Dual orexin receptor antagonists (DORAs)
The DORAs—suvorexant, lemborexant, and daridorexant—represent a newer class of medications that promote sleep by blocking wake-promoting orexin receptors. They are generally well tolerated by older adults and are effective for both sleep onset and maintenance. Although the main concern is somnolence, these medications are less likely to impair next-day cognition and have low potential for abuse and physiological dependence. Lemborexant has shown particularly promising results in older populations, with reduced sleep latency and minimal residual sedation (Gotfried MH et al, Drugs Aging 2024;41(9):741–752).

Avoid DORAs in patients with narcolepsy and use cautiously in patients who have hepatic impairment or are taking CYP3A4 inhibitors. Rare side effects include sleep paralysis and hypnagogic/hypnopompic hallucinations (dose-related risk). 

Melatonin and melatonin agonists
Melatonin is a naturally occurring hormone that helps regulate circadian rhythms. Over-the-counter (OTC) melatonin is widely used, though it lacks standardized dosing and the quality can vary across brands. Start with low doses (0.5–1 mg) 1–2 hours before bedtime.

Ramelteon is a prescription melatonin agonist that has shown a more consistent and significant effect on sleep onset latency compared to melatonin (Maruani J et al, J Sleep Res 2023;32(6):e13939). However, avoid it in patients on strong CYP1A2 inhibitors (eg, fluvoxamine) and in those with severe hepatic impairment.

Antihistamines
Many OTC sleep aids contain sedating antihistamines such as diphenhydramine, doxylamine, and hydroxyzine. These medications are problematic in older adults due to their anticholinergic effects, which can cause confusion, cognitive impairment, delirium, urinary retention, and constipation.

Antipsychotics
Quetiapine is sometimes used off-label for sleep. Given its risk of metabolic side effects, orthostasis, and oversedation, it is generally not recommended unless needed for another indication.

For all hypnotics, instruct your patients to take them within 30 minutes of bedtime and to avoid meals right before bedtime, as this can delay the onset of sleep. If insomnia persists after 7–10 days of treatment, reevaluate for other causes.

Carlat Take: Treat the root causes of insomnia and use nonpharmacologic interventions before prescribing medications. If pharmacotherapy is necessary, melatonin or ramelteon, low-dose doxepin, or a DORA may be safest for most older adults. Whatever you choose, use it briefly, at the lowest effective dose, and monitor closely.