What is the treatment of choice for an adult patient with chronic insomnia characterized by difficulty with sleep onset and sleep maintenance?

Treatment of Chronic Insomnia with Sleep Onset and Maintenance Difficulties

Primary Recommendation

For chronic insomnia affecting both sleep onset and maintenance, cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment, and when pharmacotherapy is needed, eszopiclone, zolpidem, or temazepam are the recommended options. 1, 2

Treatment Algorithm

Step 1: First-Line Non-Pharmacological Treatment

• CBT-I should be initiated as the preferred initial intervention for all patients with chronic insomnia, including those with both sleep onset and maintenance problems 1, 2, 3
• CBT-I components include:
  • Stimulus control therapy (associating bed with sleep only) 2, 3
  • Sleep restriction therapy (limiting time in bed to actual sleep time) 2, 3
  • Cognitive therapy (addressing negative thought patterns about sleep) 2, 3
  • Relaxation techniques 2, 3
• CBT-I provides sustained benefits without tolerance or adverse effects, unlike pharmacological options 1
• Sleep hygiene alone is insufficient but should be combined with other CBT-I components 2

Step 2: Pharmacological Treatment When CBT-I is Insufficient or Unavailable

When CBT-I fails, is unavailable, or the patient cannot access or participate in it, pharmacotherapy becomes appropriate 4, 5

For Combined Sleep Onset AND Maintenance Insomnia:

The three recommended medications are:

1. Eszopiclone (2-3 mg) 4, 1, 2
2. Zolpidem (10 mg) 4, 1, 2, 6
3. Temazepam (15-30 mg; 7.5 mg for elderly/debilitated) 4, 1, 2

Clinical context for selection:

• Zolpidem has FDA approval specifically for insomnia characterized by difficulties with sleep initiation and has demonstrated efficacy for up to 35 days in controlled trials 6
• Zolpidem 10 mg showed superiority over placebo on sleep latency for 4 weeks and sleep efficiency for weeks 2 and 4 in chronic insomnia patients 6
• All three medications preserve sleep architecture without significant disruption of deep sleep or REM sleep 6

Step 3: Alternative Pharmacological Options

If the primary three medications are contraindicated or ineffective:

For predominantly sleep onset problems:

• Zaleplon (10 mg) 4, 2
• Ramelteon (8 mg) 4, 2
• Triazolam (0.25 mg) 4, 2, 5

For predominantly sleep maintenance problems:

• Suvorexant (orexin receptor antagonist) 4, 1, 7
• Doxepin (3-6 mg) 4, 1, 2

Step 4: Medications to Avoid

The following should NOT be used for chronic insomnia:

• Trazodone (despite common clinical use at 50 mg) 4, 1, 2
• Diphenhydramine and other antihistamines 4, 1, 2
• Melatonin (2 mg dose) 4, 1, 2
• Tiagabine 4, 1
• Tryptophan 4, 1, 2
• Valerian 4, 1, 2
• Barbiturates and chloral hydrate 2

Critical Clinical Considerations

Strength of Evidence Caveat

All pharmacological recommendations carry a "WEAK" rating according to GRADE methodology, meaning benefits outweigh harms but many patients might reasonably choose not to use these treatments 4, 1

Duration and Monitoring

• Benzodiazepines and benzodiazepine receptor agonists are suitable for short-term treatment (up to 4 weeks) 5
• Zolpidem is FDA-approved for short-term treatment with efficacy demonstrated up to 35 days 6
• Follow patients every few weeks initially to assess effectiveness, side effects, and ongoing medication need 2
• Longer-term use may be appropriate in select cases but requires careful individual risk-benefit assessment 5

Safety Concerns

• Next-day residual effects: Zolpidem shows small but statistically significant decreases in performance on cognitive testing in some studies 6
• Anterograde amnesia: Can occur with zolpidem, predominantly at doses above 10 mg, particularly when information is presented during peak drug effect (90 minutes post-dose) 6
• Rebound insomnia: No objective evidence at recommended doses, though subjective impairment may occur in elderly patients on the first post-treatment night at doses above 5 mg 6

Combination Therapy

• Pharmacological treatment should be supplemented with behavioral and cognitive therapies when possible 2
• This combined approach may provide better outcomes than either modality alone 3, 8

Patient Education Requirements

• Treatment goals and realistic expectations 2
• Safety concerns and potential side effects 2
• Drug interactions 2
• Potential for rebound insomnia upon discontinuation 2

Common Pitfalls to Avoid

• Do not prescribe trazodone despite its widespread off-label use—it lacks evidence for efficacy in insomnia 4, 2
• Do not recommend over-the-counter antihistamines for chronic insomnia management 4, 2
• Do not use sleep hygiene education as monotherapy—it must be combined with other interventions 2
• Do not continue pharmacotherapy indefinitely without reassessment—regular monitoring is essential 2