What are the recommended medications and treatment options for a patient with insomnia?

Medications for Insomnia

For primary insomnia, start with short-intermediate acting benzodiazepine receptor agonists (zolpidem, eszopiclone, zaleplon) or ramelteon as first-line pharmacotherapy, always supplemented with Cognitive Behavioral Therapy for Insomnia (CBT-I). 1

First-Line Pharmacotherapy Options

The American Academy of Sleep Medicine establishes a clear medication hierarchy for primary insomnia: 1

Preferred Initial Agents

• Zolpidem 10 mg (5 mg in elderly): Effective for both sleep onset and maintenance, with proven efficacy in reducing sleep latency and improving total sleep time over 6 months without tolerance development 2, 3
• Eszopiclone 2-3 mg: Superior for sleep maintenance insomnia, uniquely effective for long-term use (up to 12 months) with demonstrated improvement in next-day functioning 4, 5
• Zaleplon 10 mg: Best for sleep onset difficulty only, with ultra-short half-life minimizing next-day sedation 1, 4
• Ramelteon 8 mg: Zero addiction potential, FDA-approved for sleep onset insomnia, particularly suitable for patients with substance abuse history 6, 7

The choice between these agents depends on the specific sleep complaint: use zaleplon or ramelteon for sleep onset problems, and eszopiclone or zolpidem for sleep maintenance issues. 1, 4

Critical Dosing for Elderly Patients (≥65 years)

• Zolpidem must be reduced to 5 mg maximum due to increased fall risk and cognitive impairment 8, 4
• Consider ramelteon 8 mg or low-dose doxepin 3 mg as safest options in this population 7, 8

Second-Line Options

If first-line agents fail or are contraindicated: 1

Sedating Antidepressants

Use primarily when comorbid depression/anxiety exists: 1

• Low-dose doxepin 3-6 mg: Specifically recommended for sleep maintenance, reduces wake after sleep onset by 22-23 minutes with minimal anticholinergic effects at low doses 8, 4
• Trazodone: Explicitly NOT recommended by the American Academy of Sleep Medicine due to lack of efficacy data and significant fall risk 7, 8
• Mirtazapine, amitriptyline: Consider only with comorbid mood disorders 1

Newer Agents

• Suvorexant 10-20 mg: Orexin receptor antagonist effective for sleep maintenance, reduces wake time by 16-28 minutes through different mechanism than traditional hypnotics 8, 4
• Lemborexant: Similar mechanism to suvorexant with pharmacokinetic advantages 4

Third-Line and Beyond

Combined BzRA/ramelteon plus sedating antidepressant may be considered if monotherapy fails, though this significantly increases risks. 1

Other sedating agents (gabapentin, tiagabine, quetiapine, olanzapine) should only be used when patients have comorbid conditions benefiting from the primary drug action—the American Academy of Sleep Medicine explicitly warns against off-label antipsychotic use for primary insomnia due to weak evidence and significant metabolic side effects. 1, 7

Medications to Explicitly AVOID

The following are NOT recommended for chronic insomnia: 1, 7

• Over-the-counter antihistamines (diphenhydramine, doxylamine): Lack efficacy data, cause daytime sedation, confusion, urinary retention, and tolerance develops after 3-4 days 7, 8
• Herbal supplements (valerian) and melatonin supplements: Insufficient efficacy and safety data 1, 8
• Barbiturates and chloral hydrate: Outdated with unacceptable safety profiles 1
• Long-acting benzodiazepines (lorazepam, diazepam, clonazepam): Half-lives >24 hours cause accumulation, increased fall risk, and cognitive impairment without clear benefit over shorter-acting agents 7, 8

Essential Non-Pharmacologic Component

CBT-I must be implemented before or alongside any pharmacotherapy—it represents the standard of care with superior long-term efficacy compared to medications alone. 1, 7 Components include: 7, 4

• Stimulus control therapy
• Sleep restriction therapy
• Relaxation techniques
• Cognitive restructuring
• Sleep hygiene education (insufficient as monotherapy but essential supplement)

Critical Prescribing Guidelines

When prescribing any sleep medication: 1

1. Use the lowest effective dose for the shortest duration (typically <4 weeks for acute insomnia) 8, 9
2. Follow patients every few weeks initially to assess effectiveness, side effects, and continued need 1
3. Educate patients about: treatment goals, safety concerns (complex sleep behaviors, driving impairment), potential side effects, rebound insomnia risk, and importance of behavioral treatments 1, 8
4. Taper medication when conditions allow—facilitated by concurrent CBT-I 1
5. Reassess after 7-10 days—if insomnia persists, evaluate for underlying sleep disorders (sleep apnea, restless legs syndrome) 8, 4

Long-Term Management

Chronic hypnotic medication may be indicated for severe/refractory insomnia or chronic comorbid illness, but requires: 1

• Consistent follow-up with ongoing effectiveness assessment
• Monitoring for adverse effects
• Evaluation for new/worsening comorbid disorders
• Adequate trial of CBT-I during pharmacotherapy
• Administration may be nightly, intermittent (3 nights/week), or as-needed

Common Pitfalls to Avoid

• Starting pharmacotherapy without CBT-I: Behavioral interventions provide more sustained effects than medication alone 7, 4
• Using standard adult doses in elderly: Age-adjusted dosing is mandatory (e.g., zolpidem 5 mg maximum) 8, 4
• Combining multiple sedatives: Dramatically increases risks of falls, fractures, cognitive impairment, and complex sleep behaviors 8, 4
• Continuing medication without regular reassessment: Leads to unnecessary long-term use and increased adverse effects 1, 8
• Prescribing trazodone or OTC antihistamines: Despite common practice, these lack evidence and carry significant risks 7, 8