What medication is recommended to prolong sleep in an adult with difficulty staying asleep and no contraindications such as severe liver disease, untreated sleep apnea, substance use disorder, or pregnancy?

Medication to Prolong Sleep

For adults with difficulty staying asleep (sleep-maintenance insomnia), low-dose doxepin 3–6 mg at bedtime is the single best first-line medication, demonstrating a 22–23 minute reduction in wake after sleep onset with minimal anticholinergic effects, no abuse potential, and superior safety compared to all alternatives. 1

Foundational Requirement: Cognitive Behavioral Therapy for Insomnia (CBT-I)

• All pharmacotherapy must be combined with CBT-I from the outset—medication alone produces inferior long-term outcomes, whereas CBT-I provides sustained benefits that persist after drug discontinuation. 1, 2
• CBT-I core components include stimulus control (use bed only for sleep, leave bed if awake >20 minutes), sleep restriction (limit time-in-bed to actual sleep time + 30 minutes), relaxation techniques, and cognitive restructuring of negative sleep beliefs. 1
• CBT-I can be delivered via individual therapy, group sessions, telephone, web-based modules, or self-help books—all formats demonstrate comparable efficacy. 1

First-Line Pharmacologic Option for Sleep Maintenance

Low-Dose Doxepin (3–6 mg)

• Start doxepin 3 mg at bedtime; if insufficient after 1–2 weeks, increase to 6 mg. 1, 3
• Reduces wake after sleep onset by 22–23 minutes (95% CI: 14–30 minutes) and increases total sleep time by 26–32 minutes (95% CI: 18–40 minutes) versus placebo. 1
• At hypnotic doses (3–6 mg), doxepin exhibits minimal anticholinergic activity, making it especially suitable for older adults and those transitioning off antihistamines like diphenhydramine. 1
• No abuse potential, no DEA scheduling, and no withdrawal syndrome—can be used long-term when combined with CBT-I. 1
• Particularly appropriate for elderly patients (≥65 years) due to minimal fall risk and cognitive impairment compared to benzodiazepines or Z-drugs. 1

Alternative Second-Line Options (If Doxepin Fails or Is Contraindicated)

Suvorexant (Orexin Receptor Antagonist)

• Suvorexant 10 mg at bedtime reduces wake after sleep onset by 16–28 minutes through a completely different mechanism than benzodiazepine-type agents. 1, 3
• Lower risk of cognitive and psychomotor impairment compared to benzodiazepine receptor agonists. 1
• Primary adverse effect is daytime somnolence (7% vs 3% placebo). 1
• Note: American Academy of Sleep Medicine rates this as a WEAK recommendation due to low overall quality of evidence. 3

Eszopiclone (Benzodiazepine Receptor Agonist)

• Eszopiclone 2 mg at bedtime (1 mg if age ≥65 years or hepatic impairment) for combined sleep-onset and sleep-maintenance insomnia. 1
• Increases total sleep time by 28–57 minutes and produces moderate-to-large improvements in subjective sleep quality. 1
• If 2 mg is tolerated but insufficient after 1–2 weeks, increase to 3 mg (maximum 2 mg for age ≥65 years). 1
• Take within 30 minutes of bedtime with at least 7 hours remaining before planned awakening. 1
• Higher risk profile than doxepin: carries FDA warnings for complex sleep behaviors (sleep-driving, sleep-walking), falls, fractures, and cognitive impairment. 1

Temazepam (Benzodiazepine)

• Temazepam 15 mg at bedtime (7.5 mg in elderly) for sleep-onset and maintenance insomnia with short-to-intermediate acting properties. 3
• Reduces sleep latency by 40–45 minutes and increases total sleep time by 53–54.6 minutes at 30 mg dose. 3
• Maximum dose is 30 mg—escalate only if 15 mg proves insufficient after adequate trial. 3
• Significant risks: dependence, withdrawal reactions, cognitive impairment, falls, and possible dementia associations in observational studies. 1

Medications Explicitly NOT Recommended for Sleep Maintenance

Trazodone

• The American Academy of Sleep Medicine explicitly recommends AGAINST trazodone for sleep-maintenance insomnia. 1
• Provides only ~10 minute reduction in sleep latency and ~8 minutes reduction in wake after sleep onset, with no improvement in subjective sleep quality. 1
• Adverse events occur in ~75% of older adults (headache ~30%, somnolence ~23%). 1
• Harms outweigh minimal benefits. 1

Short-Acting Agents (Inappropriate for Maintenance)

• Zaleplon, triazolam, and ramelteon are NOT recommended for early awakening insomnia due to their short duration of action (half-life ~1 hour). 3
• These agents are designed for sleep-onset only and will not address wake after sleep onset. 1

Over-the-Counter Antihistamines

• Diphenhydramine and doxylamine are NOT recommended due to lack of efficacy data, strong anticholinergic effects (confusion, urinary retention, falls), and tolerance development after only 3–4 days. 1
• The 2019 Beers Criteria carry a strong recommendation to avoid in older adults. 1

Antipsychotics

• Quetiapine and olanzapine should NOT be used for primary insomnia due to weak evidence and significant risks (weight gain, metabolic syndrome, extrapyramidal symptoms, increased mortality in elderly with dementia). 1

Traditional Long-Acting Benzodiazepines

• Lorazepam, clonazepam, and diazepam should be avoided as first-line treatment due to long half-lives leading to drug accumulation, prolonged daytime sedation, higher fall and cognitive-impairment risk, and associations with dementia and fractures. 1

Critical Safety Monitoring and Duration

• Reassess after 1–2 weeks to evaluate effects on wake after sleep onset, total sleep time, nocturnal awakenings, and daytime functioning. 1
• Screen for complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating) at every visit; discontinue medication immediately if identified. 1
• Use the lowest effective dose for the shortest necessary duration; FDA labeling indicates hypnotics are intended for short-term use (≤4 weeks) for acute insomnia. 1
• If insomnia persists beyond 7–10 days despite treatment, evaluate for comorbid sleep disorders (sleep apnea, restless-legs syndrome, periodic limb movement disorder, circadian-rhythm disorders). 1
• All hypnotics carry risks: daytime impairment, driving impairment, falls, fractures, cognitive decline; observational data link their use to dementia and major injuries. 1

Dose Adjustments for Special Populations

• Elderly (≥65 years): doxepin maximum 6 mg, eszopiclone maximum 2 mg, temazepam start 7.5 mg. 1, 3
• Hepatic impairment: eszopiclone maximum 2 mg due to reduced drug clearance. 1
• Avoid alcohol and other CNS depressants while using these medications—markedly increases risk of respiratory depression and complex sleep behaviors. 1

Common Pitfalls to Avoid

• Starting hypnotic therapy without first implementing CBT-I—leads to less durable benefit and higher relapse rates. 1
• Using adult dosing in older adults—age-adjusted dosing is essential to reduce fall risk. 1
• Combining multiple sedative agents—markedly increases risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors. 1
• Prescribing trazodone, OTC antihistamines, or antipsychotics despite lack of efficacy and significant safety concerns. 1
• Failing to reassess pharmacotherapy regularly (every 2–4 weeks) to evaluate efficacy, side effects, and ongoing medication need. 1