What are the recommended pharmacologic treatments for chronic insomnia in an adult patient?

Pharmacologic Treatment for Chronic Insomnia in Adults

First-Line Treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I)

Before prescribing any medication, all adults with chronic insomnia must receive Cognitive Behavioral Therapy for Insomnia (CBT-I) as the initial intervention. 1, 2, 3

• CBT-I demonstrates superior long-term efficacy compared to medications, with sustained benefits after treatment discontinuation, whereas medication effects cease once stopped 1, 3
• CBT-I reduces sleep onset latency by approximately 19 minutes, wake after sleep onset by 26 minutes, and improves sleep efficiency by nearly 10% 3
• Core components include stimulus control therapy (use bed only for sleep, leave bed if unable to sleep within 20 minutes), sleep restriction therapy (limit time in bed to match actual sleep time plus 30 minutes), cognitive restructuring of maladaptive sleep beliefs, relaxation techniques, and sleep hygiene education 1, 2, 4
• CBT-I can be delivered through individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats demonstrate comparable effectiveness 5, 2

First-Line Pharmacotherapy (When CBT-I Alone Is Insufficient)

When pharmacotherapy is necessary after initiating CBT-I, short- or intermediate-acting benzodiazepine receptor agonists (BzRAs) or ramelteon are recommended as first-line agents. 1, 5, 2

For Sleep-Onset Insomnia:

• Zolpidem 10 mg (5 mg for adults ≥65 years) reduces sleep onset latency by approximately 25 minutes and increases total sleep time by 29 minutes; take within 30 minutes of bedtime with at least 7 hours remaining before awakening 5, 6
• 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-night dosing when ≥4 hours remain before awakening 5, 7
• 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 5, 2

For Sleep-Maintenance Insomnia:

• Low-dose doxepin 3–6 mg reduces wake after sleep onset by 22–23 minutes through selective H₁-histamine antagonism, with minimal anticholinergic effects at hypnotic doses and no abuse potential 5, 2
• Suvorexant 10 mg (orexin receptor antagonist) reduces wake after sleep onset by 16–28 minutes and carries lower risk of cognitive and psychomotor impairment than benzodiazepine-type agents 5

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 improvements in subjective sleep quality 5, 8
• Temazepam 15 mg is effective for both sleep onset and maintenance 5

Second-Line Pharmacotherapy

If first-line BzRAs fail or are contraindicated, consider alternative agents within the same class before moving to sedating antidepressants. 5, 2

• Sedating antidepressants (trazodone, mirtazapine) may be considered when comorbid depression or anxiety is present 1, 5
• Doxepin 3–6 mg is specifically recommended for sleep maintenance insomnia as a second-line option 5, 2

Medications Explicitly NOT Recommended

The following agents should be avoided for chronic insomnia treatment: 1, 5, 2

• Trazodone – produces only ~10 minutes reduction in sleep latency with no improvement in subjective sleep quality; harms outweigh minimal benefits 5
• Over-the-counter antihistamines (diphenhydramine, doxylamine) – lack efficacy data, cause strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation), and tolerance develops within 3–4 days 1, 5, 2
• Antipsychotics (quetiapine, olanzapine) – weak evidence for insomnia benefit with significant risks including weight gain, metabolic dysregulation, extrapyramidal symptoms 5
• Melatonin supplements – produce only ~9 minutes reduction in sleep latency with insufficient evidence of efficacy 5
• Herbal supplements (valerian, L-tryptophan) – insufficient evidence to support use for primary insomnia 1, 5
• Tiagabine (anticonvulsant) – not recommended for sleep onset or maintenance insomnia 5

Treatment Algorithm

1. Initiate CBT-I immediately for all patients with chronic insomnia, incorporating all core components and continuing for at least 4–8 weeks to evaluate effectiveness 2, 4

2. If CBT-I alone is insufficient after adequate trial, add first-line pharmacotherapy based on symptom pattern:

   • Sleep-onset difficulty → zaleplon, ramelteon, or zolpidem (age-adjusted dosing) 5, 2
   • Sleep-maintenance difficulty → low-dose doxepin or suvorexant 5, 2
   • Combined difficulty → eszopiclone or temazepam 5, 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) 5

4. If multiple first-line agents are ineffective, consider sedating antidepressants, especially when comorbid depression or anxiety is present 5, 2

Critical Safety Considerations

• Use the lowest effective dose for the shortest duration possible (typically ≤4 weeks for acute insomnia); FDA labeling indicates hypnotics are intended for short-term use 1, 5, 2
• All BzRAs carry risks of complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating), daytime impairment, falls, fractures, and cognitive decline—especially in older adults 1, 5, 8
• Dose adjustments for special populations:
  • Adults ≥65 years: zolpidem maximum 5 mg, eszopiclone maximum 2 mg, zaleplon maximum 5 mg 5, 6, 8
  • Hepatic impairment: zaleplon dose reduced to 5 mg (clearance reduced by 70% in compensated cirrhosis, 87% in decompensated cirrhosis); eszopiclone maximum 2 mg 5, 7, 8
• Reassess after 1–2 weeks to evaluate sleep parameters, daytime functioning, and adverse effects; monitor for morning sedation, cognitive impairment, and complex sleep behaviors 5, 2
• Taper medications gradually when discontinuing to avoid rebound insomnia, using CBT-I techniques to facilitate successful cessation 5, 2

Common Pitfalls to Avoid

• Initiating pharmacotherapy without first implementing CBT-I leads to less durable benefit and violates guideline recommendations 1, 5, 2
• Using adult dosing in older adults without age-adjusted reductions (e.g., zolpidem ≤5 mg for ≥65 years) increases fall risk 5
• Combining multiple sedative agents markedly increases risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors 5
• Continuing pharmacotherapy long-term without periodic reassessment (every 2–4 weeks) to evaluate efficacy, side effects, and ongoing need 5, 2
• Prescribing agents without matching pharmacologic profile to insomnia phenotype (e.g., using zaleplon for maintenance rather than onset) 5
• Using trazodone, OTC antihistamines, or antipsychotics despite lack of efficacy and significant safety concerns 1, 5, 2
• Failing to consider drug interactions and contraindications before prescribing 5