What medication regimen is recommended for acute insomnia in an adult inpatient, including first‑line non‑benzodiazepine hypnotics, dosing, and adjustments for age, weight, liver disease, and fall risk?

Acute Inpatient Insomnia Medication Regimen

For acute insomnia in adult inpatients, initiate low-dose doxepin 3 mg at bedtime for sleep-maintenance problems or zolpidem 5–10 mg (5 mg if age ≥65 years) for sleep-onset difficulty, while concurrently starting Cognitive Behavioral Therapy for Insomnia (CBT-I) components such as stimulus control and sleep restriction. 1

First-Line Pharmacologic Options by Insomnia Phenotype

Sleep-Onset Insomnia

• Zolpidem 10 mg (5 mg for women, elderly, or debilitated patients) taken immediately before bedtime with at least 7–8 hours remaining before planned awakening reduces sleep latency by approximately 25 minutes. 1, 2
• Zaleplon 10 mg (5 mg if age ≥65 years) has an ultrashort half-life (~1 hour) providing rapid sleep initiation with minimal next-day sedation, suitable even for middle-of-night dosing when ≥4 hours remain before awakening. 1, 3
• Ramelteon 8 mg is a melatonin-receptor agonist with no abuse potential, no DEA scheduling, and no withdrawal symptoms, making it appropriate for patients with substance-use history. 1, 4

Sleep-Maintenance Insomnia

• Low-dose doxepin 3–6 mg reduces wake after sleep onset by 22–23 minutes via selective H₁-histamine antagonism, with minimal anticholinergic effects at hypnotic doses and no abuse potential. 1, 4
• Eszopiclone 2–3 mg (1 mg if age ≥65 years or hepatic impairment) increases total sleep time by 28–57 minutes and improves both sleep onset and maintenance. 1
• Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes with lower risk of cognitive and psychomotor impairment than benzodiazepine-type agents. 1

Combined Sleep-Onset and Maintenance Insomnia

• Eszopiclone 2 mg (1 mg if age ≥65 years) taken within 30 minutes of bedtime with at least 7 hours remaining before planned awakening is the preferred first-line option for combined symptoms. 1

Dose Adjustments for Special Populations

Age-Related Dosing

• All patients ≥65 years require reduced maximum doses: zolpidem ≤5 mg, eszopiclone ≤2 mg, zaleplon ≤5 mg, doxepin ≤6 mg due to increased sensitivity and fall risk. 1, 2

Hepatic Impairment

• Mild-to-moderate hepatic impairment: reduce zaleplon to 5 mg maximum (clearance reduced by 70% in compensated cirrhosis), eszopiclone to 2 mg maximum, and zolpidem to 5 mg. 1, 3, 2
• Severe hepatic impairment: avoid zaleplon entirely (clearance reduced by 87% in decompensated cirrhosis); avoid zolpidem due to encephalopathy risk. 3, 2

Weight Considerations

• Women clear zolpidem more slowly than men; the recommended initial dose is 5 mg for women versus 5–10 mg for men. 2

Fall Risk

• For patients at high fall risk (elderly, debilitated, or with balance disorders), prioritize ramelteon 8 mg or low-dose doxepin 3 mg as the safest choices due to minimal psychomotor impairment. 1

Medications Explicitly Contraindicated in Inpatient Settings

Traditional Benzodiazepines

• Lorazepam, temazepam, clonazepam, and diazepam should be avoided as first-line treatment due to long half-lives (>24 hours), drug accumulation with multiple doses, higher dependency risk, falls, cognitive impairment, respiratory depression, and associations with dementia and fractures. 1, 5

Over-the-Counter Antihistamines

• Diphenhydramine and doxylamine are contraindicated due to lack of efficacy data, strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation, delirium), and tolerance development within 3–4 days. 1, 4

Antipsychotics

• Quetiapine and olanzapine must not be used for primary insomnia; evidence of benefit is weak and they carry significant risks including weight gain, metabolic syndrome, extrapyramidal symptoms, and increased mortality in elderly patients with dementia. 1, 5

Trazodone

• Trazodone is not recommended because it yields only a ~10-minute reduction in sleep latency with no improvement in subjective sleep quality, and adverse events occur in ~75% of older adults. 1, 4

Critical Safety Monitoring

Complex Sleep Behaviors

• All benzodiazepine-receptor agonists (zolpidem, eszopiclone, zaleplon) carry FDA warnings for complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating); discontinue immediately if such behaviors occur. 1, 2
• Alcohol must be avoided while using these agents because it markedly increases the risk of complex sleep behaviors and respiratory depression. 1

Next-Day Impairment

• Zolpidem 10 mg produces measurable psychomotor and memory deficits up to 7–11.5 hours after dosing; patients often do not perceive the impairment, so driving or operating machinery should be avoided until fully awake. 1, 2
• Zaleplon demonstrates minimal next-day impairment as early as 4 hours post-dose due to its ultrashort half-life. 3

Duration of Therapy

• FDA labeling limits hypnotic use to ≤4 weeks for acute insomnia; evidence beyond this period is insufficient. 1
• Reassess after 1–2 weeks to evaluate sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and adverse effects. 1, 4

Concurrent Behavioral Therapy (Mandatory)

• CBT-I must be initiated alongside any pharmacotherapy because behavioral therapy provides superior long-term outcomes and sustained benefits after medication discontinuation. 1, 4
• Core components include: stimulus control (use bed only for sleep; leave bed if unable to fall asleep within ~20 minutes), sleep restriction (limit time in bed to approximate actual sleep time plus 30 minutes), cognitive restructuring (modify negative beliefs about sleep), and relaxation training. 1

Common Pitfalls to Avoid

• Do not prescribe hypnotics without concurrent CBT-I; this violates strong guideline recommendations and yields less durable benefit. 1
• Do not use adult dosing in elderly patients; age-adjusted dosing is mandatory to reduce fall risk. 1, 2
• Do not combine multiple sedating agents (e.g., adding a benzodiazepine to zolpidem); this markedly increases risk of respiratory depression, falls, cognitive impairment, and complex sleep behaviors. 1
• Do not continue pharmacotherapy beyond 4 weeks without documented rationale and periodic reassessment every 2–4 weeks. 1