What medications are recommended for patients who experience nocturnal awakenings?

Medications for Nocturnal Awakenings

For patients experiencing nocturnal awakenings, Cognitive Behavioral Therapy for Insomnia (CBT-I) should be used as first-line treatment, with pharmacologic options including low-dose doxepin (3-6mg), eszopiclone (2-3mg), or suvorexant (10-20mg) for sleep maintenance insomnia when non-pharmacologic approaches are insufficient. 1

First-Line Approach: Non-Pharmacologic Treatments

Cognitive Behavioral Therapy for Insomnia (CBT-I)

• Recommended as first-line treatment by both the American Academy of Sleep Medicine and American College of Physicians
• More effective than pharmacotherapy for both short-term and long-term outcomes 1
• Components include:
  • Sleep restriction
  • Stimulus control
  • Cognitive restructuring
  • Sleep hygiene education
  • Relaxation techniques

Sleep Hygiene Modifications

• Maintain consistent sleep-wake schedule
• Limit screen time before bed
• Avoid caffeine, alcohol, and large meals before bedtime
• Create a comfortable sleep environment (dark, quiet, cool)
• Consider using the "TUCK-in" protocol (timed lights-off periods, minimizing night-time noise, earplugs) 2

Pharmacologic Treatment Options

For Sleep Maintenance Insomnia (Nocturnal Awakenings)

1. Doxepin (3-6mg)

   • Low-dose formulation specifically approved for sleep maintenance
   • Lower risk of next-day impairment compared to benzodiazepines
   • Particularly suitable for elderly patients 1

2. Eszopiclone (2-3mg)

   • Non-benzodiazepine hypnotic effective for maintaining sleep
   • Longer half-life helps prevent middle-of-night awakenings 1

3. Suvorexant (10-20mg)

   • Orexin receptor antagonist
   • Specifically targets the wake-promoting system
   • Effective for sleep maintenance 1

4. Temazepam (15mg)

   • Intermediate-acting benzodiazepine
   • Use with caution due to risk of dependence and next-day impairment
   • Avoid in elderly patients due to fall risk 1

For Sleep Onset Insomnia (If Also Present)

1. Zolpidem (5-10mg)

   • 5mg for women and elderly; 5-10mg for men
   • Take immediately before bedtime with at least 7-8 hours before planned awakening
   • Effect may be delayed if taken with food 3

2. Ramelteon (8mg)

   • Melatonin receptor agonist
   • No risk of dependence (not a controlled substance)
   • Particularly useful for patients with substance use history 1

3. Low-dose melatonin (1-3mg)

   • Take 1-2 hours before bedtime
   • Lower risk of daytime sedation
   • Can be titrated up to 15mg for specific sleep disorders 1

Special Populations

Elderly Patients

• Use lower doses of all medications (zolpidem 5mg, doxepin 3mg)
• Avoid benzodiazepines due to increased risk of falls and cognitive impairment
• Prefer ramelteon or low-dose doxepin as safer alternatives 1

Patients with Substance Use History

• Prefer non-scheduled options like ramelteon or doxepin 1

Patients with Respiratory Conditions

• Use lower doses of medications
• Exercise caution with sedating medications 1

Treatment Algorithm for Nocturnal Awakenings

1. Start with CBT-I and sleep hygiene modifications for 4-6 weeks
2. If insufficient response, add pharmacotherapy:
   • For middle-of-night awakenings: Low-dose doxepin (3-6mg) or eszopiclone (2-3mg)
   • For patients with both sleep onset and maintenance issues: Consider eszopiclone or suvorexant
   • For elderly patients: Prefer doxepin at lowest effective dose (3mg)
3. Monitor for effectiveness within 2-4 weeks of starting treatment
4. Watch for side effects: daytime sedation, falls, cognitive changes 1
5. Consider referral to sleep specialist if insomnia persists or sleep-disordered breathing is suspected

Important Considerations

• Avoid benzodiazepines when possible, especially in elderly patients, due to risks of dependence, falls, and cognitive impairment 1
• For patients with PTSD-associated nightmares, prazosin is recommended (starting at 1mg at bedtime, increasing by 1-2mg every few days until effective) 4
• Patients with circadian rhythm disorders may require specialized treatments like light therapy or melatonin timed appropriately 4
• Medications should be taken as a single dose and not readministered during the same night 3

Monitoring and Follow-up

• Assess sleep parameters within 2-4 weeks of starting treatment
• Monitor for side effects, particularly daytime sedation, falls, and cognitive changes
• Schedule follow-up within 2-4 weeks after initiating any treatment 1