What are the first-line medication options for patients with sleep disturbances?

First-Line Medications for Sleep Disturbances

Cognitive Behavioral Therapy for Insomnia (CBT-I) should be the first-line treatment for all patients with sleep disturbances, with short/intermediate-acting benzodiazepine receptor agonists (BzRAs) or the orexin receptor antagonist suvorexant as first-line pharmacological options when medication is needed. 1

Non-Pharmacological First-Line Approach

CBT-I is strongly recommended as the initial treatment approach for all patients with insomnia due to its:

• Sustained benefits without risk of tolerance or adverse effects
• Multicomponent therapy that includes sleep restriction therapy, stimulus control, cognitive therapy, relaxation techniques, and sleep hygiene education

If access to traditional face-to-face CBT-I is limited, alternatives include:

• Digital CBT-I applications
• Brief Behavioral Treatment for Insomnia (BBT-I)
• Self-help CBT-I materials (books, online resources)

First-Line Pharmacological Options

When medications are needed, the following are recommended as first-line options:

For Sleep Onset Insomnia:

• Zolpidem: 10mg for adults, 5mg for elderly 1, 2

  • Reduces sleep latency effectively
  • Caution: Risk of next-morning impairment, falls, and complex sleep behaviors

• Zaleplon: 10mg 1

  • Very short half-life, specifically targets sleep onset
  • Less residual daytime effects

• Ramelteon: 8mg 1, 3

  • Non-scheduled melatonin receptor agonist
  • Good for patients with substance use history
  • Reduces sleep latency by approximately 9.6 minutes
  • Fewer side effects than BzRAs

For Sleep Maintenance Insomnia:

• Suvorexant: 10-20mg 1

  • Orexin receptor antagonist
  • Effective for sleep maintenance

• Doxepin: 3-6mg 1

  • Low-dose option effective for sleep maintenance
  • Minimal side effects
  • Safe option for lactating mothers

• Eszopiclone: 2-3mg 1

  • Effective for both sleep onset and maintenance

Medication Selection Algorithm

1. Assess insomnia type:

   • Sleep onset difficulty → Zolpidem, Zaleplon, or Ramelteon
   • Sleep maintenance difficulty → Suvorexant, Doxepin, or Eszopiclone
   • Both onset and maintenance → Eszopiclone or Zolpidem

2. Consider patient factors:

   • Elderly patients → Lower doses (e.g., Zolpidem 5mg)
   • History of substance use → Ramelteon (non-scheduled)
   • Risk of falls → Avoid benzodiazepines, consider Ramelteon or low-dose Doxepin

3. For refractory insomnia, options include 4:

   • Short-acting benzodiazepine (lorazepam)
   • Antipsychotic medications (chlorpromazine, quetiapine, olanzapine)
   • Sedating antidepressants (trazodone, mirtazapine)

Important Considerations and Cautions

• Use lowest effective dose for shortest period possible 1

  • Short-term use (<4 weeks) is generally recommended for most hypnotics
  • Administer on an empty stomach for maximum effectiveness

• Medications to avoid 1:

  • Trazodone (despite common use)
  • Diphenhydramine and other antihistamines
  • Melatonin and other herbal supplements
  • Tiagabine and tryptophan

• Special precautions:

  • Benzodiazepines should be avoided in older patients and those with cognitive impairment 4
  • Zolpidem carries risk of next-morning impairment, falls (OR 4.28), and hip fractures (RR 1.92) 5
  • Complex sleep behaviors including sleepwalking have been reported with zolpidem use 5
  • FDA has issued warnings about disruptive sleep-related behaviors with BzRA hypnotics 1

Treatment Monitoring

• Reassess treatment in 4-6 weeks
• If inadequate response, try alternative first-line agent or move to second-line options
• Continue CBT-I throughout treatment for long-term benefits
• Screen for other sleep disorders (sleep apnea, restless legs syndrome)
• Employ the lowest effective maintenance dosage and taper medication when conditions allow

By following this structured approach to managing sleep disturbances, clinicians can optimize patient outcomes while minimizing adverse effects associated with sleep medications.