What are the recommended drug therapies for insomnia?

Drug Therapy for Insomnia

Cognitive Behavioral Therapy for Insomnia (CBT-I) should be used as first-line treatment for all adults with chronic insomnia, with pharmacological therapy reserved as second-line treatment only when CBT-I alone is unsuccessful. 1, 2, 3

First-Line Pharmacotherapy Options

When medication is necessary, the recommended sequence for pharmacological treatment is:

• Short-intermediate acting benzodiazepine receptor agonists (BzRAs) or ramelteon should be used as first-line medications for patients with chronic insomnia 1, 2

• For sleep onset insomnia, consider:

  • Zaleplon (10 mg) 1, 2
  • Zolpidem (10 mg, 5 mg in elderly) 1, 2, 4
  • Ramelteon (8 mg) 1, 2, 5
  • Triazolam (0.25 mg) - though not considered first-line due to rebound anxiety 1, 2

• For sleep maintenance insomnia, consider:

  • Eszopiclone (2-3 mg) 1, 2
  • Zolpidem (10 mg, 5 mg in elderly) 1, 2, 4
  • Temazepam (15 mg) 1, 2

Second-Line Pharmacotherapy Options

If first-line medications are ineffective, consider:

• Alternative BzRAs or ramelteon if the initial agent was unsuccessful 1, 2

• Sedating antidepressants, especially for patients with comorbid depression/anxiety 1, 2:

  • Doxepin (3-6 mg) for sleep maintenance insomnia 1, 2
  • Trazodone is not recommended by the American Academy of Sleep Medicine despite common use 1, 2
  • Amitriptyline and mirtazapine may be considered 2

• Suvorexant (orexin receptor antagonist) for sleep maintenance insomnia 1, 2

Not Recommended Agents

• Over-the-counter antihistamines (e.g., diphenhydramine) are not recommended due to lack of efficacy data and safety concerns 1, 2
• Herbal supplements (e.g., valerian) and nutritional substances (e.g., melatonin) are not recommended due to insufficient evidence of efficacy 1, 2
• Tiagabine (anticonvulsant) is not recommended for sleep onset or maintenance insomnia 1, 2
• Older hypnotics including barbiturates and chloral hydrate are not recommended 1, 2

Medication Selection Considerations

• Selection should be based on 1, 2, 3:

  • Symptom pattern (sleep onset vs. maintenance difficulty)
  • Treatment goals
  • Past treatment responses
  • Patient preference
  • Cost and availability
  • Comorbid conditions
  • Contraindications
  • Potential drug interactions
  • Side effect profile

• The FDA has approved pharmacologic therapy for short-term use only (4-5 weeks) 1, 3

Important Clinical Considerations

• Zolpidem has been associated with increased risk of falls (OR 4.28), hip fractures (RR 1.92), CNS-related adverse effects (confusion, dizziness), complex sleep behaviors, and rebound insomnia 4, 6

• Ramelteon has demonstrated efficacy for sleep onset insomnia with a favorable safety profile and minimal abuse potential 5

• Non-benzodiazepine receptor agonists (zaleplon, zolpidem, eszopiclone) generally cause less disruption of normal sleep architecture than traditional benzodiazepines 7, 8

• Short-term hypnotic treatment should be supplemented with behavioral and cognitive therapies 1, 2

Common Pitfalls to Avoid

• Using sedating agents without considering their specific effects on sleep onset versus maintenance 1, 2

• Failing to consider drug interactions and contraindications, particularly in elderly patients 1, 2

• Using over-the-counter sleep aids with limited efficacy data 1, 2

• Continuing pharmacotherapy long-term without periodic reassessment 1, 2

• Not implementing CBT-I techniques alongside medication 1, 2, 3

• Prescribing higher than recommended doses, especially in elderly patients 1, 2