What is the drug of choice for treating insomnia?

Drug of Choice for Insomnia

For the treatment of insomnia in adults, non-benzodiazepine receptor agonists (specifically eszopiclone, zolpidem, and zaleplon) are the first-line pharmacological options due to their efficacy, favorable side effect profile, and lower risk of dependence compared to traditional benzodiazepines. 1, 2, 3

First-Line Pharmacological Options

Non-Benzodiazepine Receptor Agonists (Z-drugs)

• Eszopiclone (2-3 mg): Effective for both sleep onset and maintenance insomnia 1
• Zolpidem (10 mg): Effective for both sleep onset and maintenance insomnia 1
• Zaleplon (10 mg): Particularly effective for sleep onset insomnia 1

These medications are preferred because they:

• Cause less disruption of normal sleep architecture than benzodiazepines
• Have fewer psychomotor and memory impairment issues
• Show less rebound insomnia and withdrawal symptoms upon discontinuation
• Have lower abuse potential 3, 4

Second-Line Options

Orexin Receptor Antagonists

• Suvorexant (10-20 mg): Recommended primarily for sleep maintenance insomnia 1

Melatonin Receptor Agonists

• Ramelteon (8 mg): Recommended for sleep onset insomnia 1

Low-Dose Doxepin

• Doxepin (3-6 mg): Effective for sleep maintenance insomnia 1

Traditional Benzodiazepines

While effective, these should be considered only when other options have failed due to higher risk of dependence, tolerance, and side effects:

• Temazepam (15 mg): For sleep onset and maintenance insomnia 1
• Triazolam (0.25 mg): For sleep onset insomnia 1

Medications NOT Recommended for Insomnia

The American Academy of Sleep Medicine specifically recommends against:

• Trazodone (insufficient evidence for efficacy)
• Tiagabine (anticonvulsant)
• Diphenhydramine and other over-the-counter antihistamines
• Melatonin supplements
• L-tryptophan
• Valerian 1

Treatment Algorithm

1. Assess insomnia type:

   • Sleep onset insomnia: Zaleplon, zolpidem, ramelteon
   • Sleep maintenance insomnia: Eszopiclone, zolpidem, suvorexant, doxepin
   • Both: Eszopiclone, zolpidem, temazepam

2. Consider patient factors:

   • Elderly patients: Start with half the standard dose
   • History of substance abuse: Consider ramelteon (lowest abuse potential)
   • Liver impairment: Avoid or reduce doses of most agents
   • Morning activities requiring alertness: Prefer shorter-acting agents (zaleplon)

Important Caveats

• All pharmacological recommendations should be initiated at the lowest effective dose
• Short-term use (2-4 weeks) is preferred whenever possible
• Non-pharmacological approaches (cognitive behavioral therapy for insomnia, sleep hygiene) should be implemented concurrently
• Monitor for side effects including daytime sedation, cognitive impairment, and risk of falls (especially in older adults)
• Avoid combining with alcohol or other CNS depressants

Common Pitfalls to Avoid

• Using sedating antidepressants (except low-dose doxepin) or antipsychotics as first-line agents for insomnia
• Long-term use of any hypnotic without periodic reassessment
• Abrupt discontinuation of benzodiazepines after prolonged use
• Relying on over-the-counter sleep aids containing antihistamines, which can cause anticholinergic side effects and tolerance
• Using alcohol as a sleep aid, which disrupts sleep architecture and can worsen insomnia 5, 6