What are the recommended first‑line and pharmacologic treatment options for insomnia?

Treatment for Insomnia

Cognitive Behavioral Therapy for Insomnia (CBT-I) is the mandatory first-line treatment for all adults with chronic insomnia, and it must be initiated before or alongside any medication. 1, 2, 3

Why CBT-I First

• CBT-I provides superior long-term outcomes compared to pharmacotherapy, with sustained benefits persisting up to 2 years after treatment ends, whereas medication effects disappear once the drug is stopped 1, 3, 4
• The American Academy of Sleep Medicine and American College of Physicians issue a strong recommendation that CBT-I be the initial intervention for all patients with chronic insomnia due to its favorable benefit-to-risk ratio and minimal adverse effects 1, 2, 3
• CBT-I can be delivered effectively through individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats demonstrate comparable efficacy 1, 2

Core Components of CBT-I

• Stimulus control therapy: Use the bed only for sleep; leave the bed if unable to fall asleep within approximately 20 minutes 1, 2
• Sleep restriction therapy: Limit time in bed to approximate actual sleep time plus 30 minutes to consolidate sleep 1, 2
• Relaxation techniques: Progressive muscle relaxation, guided imagery, or diaphragmatic breathing 1, 2
• Cognitive restructuring: Modify negative beliefs and maladaptive thoughts about sleep 1, 3
• Sleep hygiene education: Maintain consistent bed/wake times, avoid caffeine after noon, eliminate evening alcohol, limit daytime naps to 15–20 minutes before 3 PM, avoid heavy meals within 3 hours of bedtime, and eliminate screen time for at least 1 hour before bed 1, 2

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Pharmacologic Options (Only After CBT-I Initiation)

Medications should only be considered when patients are unable to participate in CBT-I, still have symptoms despite CBT-I, or as a temporary adjunct to ongoing behavioral therapy—never as monotherapy. 1, 2, 3

First-Line Pharmacotherapy

For Sleep-Onset Insomnia

• Zolpidem 10 mg (5 mg for adults ≥65 years) shortens sleep-onset latency by approximately 25 minutes and increases total sleep time by approximately 29 minutes; take within 30 minutes of bedtime with at least 7 hours remaining before awakening 1, 2, 5
• Zaleplon 10 mg (5 mg for adults ≥65 years) has an ultrashort half-life (~1 hour), providing rapid sleep initiation with minimal next-day sedation; suitable for middle-of-the-night dosing when ≥4 hours remain before awakening 1, 2, 6
• Ramelteon 8 mg is a melatonin-receptor agonist with no abuse potential, no DEA scheduling, and no withdrawal symptoms—appropriate for patients with substance-use history 1, 2

For 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, 2, 7
• Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes and carries a lower risk of cognitive and psychomotor impairment than benzodiazepine-type agents 1, 2

For Combined Sleep-Onset and Maintenance Insomnia

• Eszopiclone 2–3 mg (1 mg for adults ≥65 years or hepatic impairment) improves both sleep onset and maintenance, increasing total sleep time by 28–57 minutes with moderate-to-large gains in subjective sleep quality 1, 2
• Zolpidem extended-release 10 mg (5 mg for adults ≥65 years) maintains therapeutic concentrations for >6 hours, supporting sleep continuity throughout the night 1, 2

Dosing Adjustments for Special Populations

• For adults ≥65 years: Maximum doses are zolpidem ≤5 mg, eszopiclone ≤2 mg, zaleplon ≤5 mg, doxepin ≤6 mg due to heightened sensitivity and fall risk 1, 2, 8
• For hepatic impairment: Eszopiclone and zaleplon maximum 2 mg and 5 mg respectively due to reduced drug clearance 1, 2

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Medications Explicitly NOT Recommended

• Trazodone yields only ~10 minutes reduction in sleep latency and ~8 minutes reduction in wake after sleep onset, with no improvement in subjective sleep quality; adverse events occur in ~75% of older adults (headache, somnolence)—the American Academy of Sleep Medicine explicitly recommends against its use for insomnia 1, 2, 3
• Over-the-counter antihistamines (diphenhydramine, doxylamine) lack efficacy data, cause strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation, delirium), and develop tolerance within 3–4 days 1, 2, 3
• Traditional benzodiazepines (lorazepam, clonazepam, diazepam, temazepam) have long half-lives leading to drug accumulation, prolonged daytime sedation, higher fall and cognitive-impairment risk, and are linked to dementia and fractures 1, 2, 8
• Antipsychotics (quetiapine, olanzapine) have weak evidence for insomnia benefit and significant risks including weight gain, metabolic dysregulation, extrapyramidal symptoms, and increased mortality in elderly patients with dementia 1, 2, 3
• Melatonin supplements produce only ~9 minutes reduction in sleep latency with insufficient efficacy data 1, 2
• Herbal supplements (valerian, L-tryptophan) have insufficient evidence to support use for primary insomnia 1, 2

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Treatment Duration and Safety Monitoring

• FDA labeling indicates hypnotics are intended for short-term use (≤4 weeks) for acute insomnia; evidence does not support routine use beyond this period 1, 2, 5, 6
• Reassess after 1–2 weeks to evaluate effects on sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and to monitor adverse effects such as morning sedation, cognitive impairment, and complex sleep behaviors 1, 2
• Screen for complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating) at every visit; discontinue the medication immediately if such behaviors are identified 1, 2
• If insomnia persists beyond 7–10 days despite appropriate therapy, evaluate for comorbid sleep disorders such as sleep apnea, restless-legs syndrome, periodic limb movement disorder, or circadian-rhythm disorders 1, 2
• All hypnotics carry risks including daytime impairment, driving impairment, falls, fractures, cognitive decline; observational data link their use to dementia and major injuries 1, 2, 8
• Prescribe the lowest effective dose for the shortest necessary duration, consider periodic "drug holidays," and taper gradually to avoid rebound insomnia 1, 2

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Stepwise Treatment Algorithm

1. Initiate CBT-I immediately for all patients with chronic insomnia, incorporating stimulus control, sleep restriction, relaxation, cognitive restructuring, and sleep-hygiene education 1, 2, 3

2. Add first-line pharmacotherapy if CBT-I alone is insufficient after 4–8 weeks:

   • Sleep-onset difficulty → zaleplon, ramelteon, or zolpidem (dose adjusted for age) 1, 2
   • Sleep-maintenance difficulty → low-dose doxepin or suvorexant 1, 2
   • Combined difficulty → eszopiclone or zolpidem extended-release 1, 2

3. If the chosen first-line agent fails after 1–2 weeks, switch to an alternative agent within the same class (e.g., zaleplon → zolpidem for onset; doxepin → suvorexant for maintenance) 1, 2

4. If multiple first-line agents are ineffective, consider alternative orexin-receptor antagonists or sedating antidepressants only when comorbid depression or anxiety is present 1, 2

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Common Pitfalls to Avoid

• Initiating pharmacotherapy without first employing CBT-I, which provides more durable benefits than medication alone 1, 2, 3
• Using adult dosing in older adults; age-adjusted dosing (e.g., zolpidem ≤5 mg for ≥65 years) is essential to reduce fall risk 1, 2, 8
• Combining multiple sedative agents, which markedly increases the risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors 1, 2
• Failing to reassess pharmacotherapy regularly (every 2–4 weeks) to evaluate efficacy, side effects, and to plan tapering 1, 2
• Prescribing agents without matching their pharmacologic profile to the specific insomnia phenotype (e.g., using zaleplon for maintenance rather than onset) 1, 2
• Using trazodone, OTC antihistamines, antipsychotics, or traditional benzodiazepines for primary insomnia despite lack of efficacy and significant safety concerns 1, 2, 3
• Continuing pharmacotherapy long-term without periodic reassessment and attempts at tapering 1, 2