What are the recommended treatment options for an adult patient with insomnia and no significant medical history?

Medications for Insomnia in Adults

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

All adults with chronic insomnia should receive CBT-I as initial treatment before or alongside any pharmacotherapy, as it demonstrates superior long-term efficacy with sustained benefits after medication discontinuation. 1, 2

• CBT-I includes stimulus control therapy (going to bed only when sleepy, using bed only for sleep/sex), sleep restriction therapy (limiting time in bed to actual sleep time), relaxation techniques (progressive muscle relaxation, guided imagery), and cognitive restructuring of negative thoughts about sleep 2
• CBT-I can be delivered through individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats show effectiveness 2
• Sleep hygiene education alone is insufficient as monotherapy but should supplement other CBT-I components: avoiding caffeine/alcohol in evening, maintaining consistent sleep-wake times, limiting daytime naps to 30 minutes before 2 PM, keeping bedroom quiet and temperature-regulated 2

First-Line Pharmacotherapy Options

For Sleep Onset Insomnia

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

• Zolpidem 10 mg (5 mg in elderly/women) reduces sleep latency by 25 minutes and improves total sleep time by 29 minutes 2, 3
• Zaleplon 10 mg (5 mg in elderly) has very short half-life with minimal residual sedation, specifically for sleep onset 1, 2
• Eszopiclone 2-3 mg improves both sleep onset and maintenance with 28-57 minute increase in total sleep time 1, 2, 4
• Ramelteon 8 mg is a melatonin receptor agonist with zero addiction potential, particularly suitable for patients with substance use history 2

For Sleep Maintenance Insomnia

Low-dose doxepin 3-6 mg is the preferred first-line option specifically for sleep maintenance, demonstrating 22-23 minute reduction in wake after sleep onset with minimal side effects and no abuse potential. 1, 2

• Eszopiclone 2-3 mg addresses both sleep onset and maintenance 1, 4
• Zolpidem 10 mg (5 mg in elderly) effective for maintenance as well as onset 2, 3
• Suvorexant 10 mg (orexin receptor antagonist) reduces wake after sleep onset by 16-28 minutes through different mechanism 1, 2

Critical Dosing Adjustments

• Elderly patients (≥65 years): Zolpidem maximum 5 mg, eszopiclone 1-2 mg maximum, ramelteon 8 mg or low-dose doxepin 3 mg are safest choices due to minimal fall risk 2
• Women: FDA requires lower doses due to slower drug clearance—zolpidem 5 mg maximum 2
• Hepatic impairment: Eszopiclone 1 mg maximum, zaleplon 5 mg maximum 2

Medications Explicitly NOT Recommended

The following agents should NOT be used for insomnia treatment: 1, 2

• Trazodone: Minimal benefit (10 minutes reduction in sleep latency) with no improvement in subjective sleep quality, harms outweigh benefits 1, 2
• Diphenhydramine (Benadryl) and other antihistamines: No efficacy data, strong anticholinergic effects causing confusion/urinary retention/falls in elderly, tolerance develops after 3-4 days 1, 2
• Melatonin supplements: Only 9 minutes reduction in sleep latency with insufficient evidence 1, 2
• Valerian and L-tryptophan: Insufficient evidence of efficacy 1, 2
• Traditional benzodiazepines (lorazepam, clonazepam, diazepam): Higher risk of dependency, falls, cognitive impairment, respiratory depression, and prolonged daytime sedation compared to non-benzodiazepines 2
• Antipsychotics (quetiapine, olanzapine): Weak evidence, significant metabolic side effects including weight gain and metabolic syndrome 2

Treatment Algorithm

1. Initiate CBT-I immediately for all patients with chronic insomnia 1, 2
2. If CBT-I insufficient after 4-8 weeks, add pharmacotherapy based on symptom pattern:
   • Sleep onset difficulty: Zaleplon 10 mg, ramelteon 8 mg, or zolpidem 5-10 mg 2
   • Sleep maintenance difficulty: Low-dose doxepin 3-6 mg (preferred), eszopiclone 2-3 mg, or suvorexant 10 mg 2
   • Both onset and maintenance: Eszopiclone 2-3 mg or zolpidem 10 mg 2
3. If first-line BzRA unsuccessful, try alternative BzRA from same class 2
4. If BzRAs fail or contraindicated, consider sedating antidepressants (particularly with comorbid depression/anxiety) 2

Critical Safety Warnings and Monitoring

All BzRAs carry FDA black box warnings for complex sleep behaviors including sleep-driving, sleep-walking, and sleep-eating—patients must be warned and medication stopped immediately if these occur. 2, 3

• Take medication only when able to stay in bed 7-8 hours before needing to be active 3
• Take on empty stomach at bedtime, not after meals, for faster sleep onset 3
• Avoid alcohol and other CNS depressants due to additive respiratory depression and cognitive impairment 2, 3
• Monitor for: Daytime somnolence, driving impairment, falls (especially elderly), cognitive/behavioral changes, complex sleep behaviors 2
• Reassess after 1-2 weeks to evaluate efficacy on sleep parameters and daytime functioning 2

Duration of Treatment

• Use lowest effective dose for shortest duration possible 2
• Insomnia persisting beyond 7-10 days requires evaluation for underlying sleep disorders (sleep apnea, restless legs syndrome, circadian rhythm disorders) 2
• Long-term use (>4 weeks): Insufficient evidence for routine long-term pharmacotherapy; if continued, document why CBT-I alone is insufficient, implement periodic "drug holidays" to assess ongoing need 2
• Discontinuation: Gradual tapering recommended to prevent withdrawal symptoms; CBT-I facilitates successful discontinuation 2

Special Population Considerations

• Substance use history: Ramelteon only appropriate choice due to zero abuse potential and non-DEA-scheduled status 2
• Comorbid depression/anxiety: Sedating antidepressants (low-dose doxepin, mirtazapine) address both conditions simultaneously 2
• Respiratory disorders (sleep apnea, COPD): Non-benzodiazepines preferred due to minimal respiratory depression 2
• Pregnancy (third trimester): Zolpidem may cause breathing difficulties or excess sleepiness in newborn; monitor infant for sleepiness, trouble breathing, or limpness 3

Common Pitfalls to Avoid

• Failing to initiate CBT-I before or alongside pharmacotherapy—behavioral interventions provide more sustained effects than medication alone 2
• Using doses appropriate for younger adults in elderly patients—zolpidem requires age-adjusted dosing (5 mg maximum in elderly) 2
• Prescribing traditional benzodiazepines as first-line treatment—observational studies link benzodiazepine use to increased dementia risk, fractures, and major injuries 2
• Continuing pharmacotherapy long-term without periodic reassessment of ongoing need and efficacy 2
• Combining multiple sedative medications—significantly increases risks of complex sleep behaviors, cognitive impairment, falls, and fractures 2