What are the guidelines for the pharmacological management of insomnia?

Pharmacological Management of Insomnia

Cognitive Behavioral Therapy for Insomnia (CBT-I) should be the first-line treatment for all patients with chronic insomnia, with pharmacotherapy reserved for patients who cannot access CBT-I, fail to respond to it, or as a temporary adjunct to CBT-I. 1, 2

Treatment Algorithm

First-Line Approach

• CBT-I is the initial treatment for all adults with chronic insomnia due to its superior long-term efficacy and minimal risk of adverse effects 1, 3
• Pharmacotherapy should only be considered when patients are unable to participate in CBT-I, still have symptoms despite CBT-I, or as a temporary adjunct to CBT-I 3

First-Line Pharmacological Options

• Short/intermediate-acting benzodiazepine receptor agonists (BzRAs) or ramelteon are recommended as first-line medications when pharmacotherapy is necessary 2, 3

• For sleep onset insomnia, consider:

  • Zaleplon (10 mg) 2
  • Ramelteon (8 mg) - particularly beneficial due to lack of abuse potential 2, 4
  • Zolpidem (10 mg, 5 mg in elderly) 2, 5
  • Triazolam (0.25 mg) - though associated with rebound anxiety 2

• For sleep maintenance insomnia, consider:

  • Eszopiclone (2-3 mg) 2, 6
  • Zolpidem (10 mg, 5 mg in elderly) 2, 5
  • Temazepam (15 mg) 2
  • Low-dose doxepin (3-6 mg) 2
  • Suvorexant (orexin receptor antagonist) 2

Second-Line Options

• Sedating antidepressants (when comorbid depression/anxiety exists) 2, 7:
  • Doxepin liquid (3-6 mg) - particularly effective for sleep maintenance 7
  • Mirtazapine - beneficial with comorbid depression 7
  • Trazodone (typically 50 mg) - though evidence is more limited 7

Not Recommended Agents

• Over-the-counter antihistamines (e.g., diphenhydramine) - lack of efficacy data and safety concerns 2, 7
• Herbal supplements (e.g., valerian) and nutritional substances (e.g., melatonin) - insufficient evidence of efficacy 2, 3
• Tryptophan - not recommended for sleep onset or maintenance insomnia 3
• Tiagabine (anticonvulsant) - not recommended for sleep onset or maintenance insomnia 2
• Older hypnotics including barbiturates and chloral hydrate 2

Special Considerations

Elderly Patients

• Use lower doses of all medications due to increased sensitivity to side effects 7, 2
• Be particularly cautious with benzodiazepines and non-benzodiazepine hypnotics due to increased risks of falls, cognitive impairment, and dependence 1, 2

Administration Considerations

• For patients requiring administration through feeding tubes, doxepin liquid is ideal; alternatively, trazodone and mirtazapine can be crushed and dissolved in water 7
• Start with the lowest effective dose and titrate as needed 7

Monitoring and Follow-up

• Assess efficacy after 1-2 weeks of treatment initiation 7, 8
• Long-term prescribing should include consistent follow-up and monitoring for adverse effects 7, 2
• Regular reassessment is essential to determine ongoing need for medication 2

Common Pitfalls to Avoid

• Using sedating agents without considering their specific effects on sleep onset versus maintenance 2
• Failing to consider drug interactions and contraindications 2
• Using over-the-counter sleep aids with limited efficacy data 2, 7
• Continuing pharmacotherapy long-term without periodic reassessment 2
• Neglecting to implement CBT-I techniques alongside medication 1, 8

Evidence Quality and Limitations

• Most hypnotic medications have only been studied for short-term use (4-5 weeks), despite insomnia often being a chronic condition 5, 6, 8
• The American Academy of Sleep Medicine notes that their recommendations for most medications are "weak" due to limited long-term efficacy and safety data 3
• Recent systematic reviews highlight the need for more rigorous trials comparing different pharmacological options 9, 10