What are the recommended medications for treating insomnia?

Recommended Medications for Treating Insomnia

The first-line pharmacological treatment for insomnia is short-intermediate acting benzodiazepine receptor agonists (BzRAs) such as zolpidem, eszopiclone, zaleplon, and temazepam, or the melatonin receptor agonist ramelteon, though cognitive behavioral therapy for insomnia (CBT-I) should be considered before medications whenever possible. 1, 2, 3

First-Line Treatment Approach

• CBT-I should be the initial treatment for all adults with chronic insomnia due to its superior long-term efficacy and minimal risk of adverse effects 3, 4
• When pharmacotherapy is necessary, the following medication classes are recommended in sequence:

First-Line Pharmacological Options

• Short-intermediate acting benzodiazepine receptor agonists (BzRAs):

  • Zolpidem: 10 mg (5 mg in elderly) for sleep onset and maintenance insomnia 1, 2, 5
  • Eszopiclone: 2-3 mg for sleep onset and maintenance insomnia 2, 6
  • Zaleplon: 10 mg for sleep onset insomnia 2
  • Temazepam: 15 mg for sleep onset and maintenance insomnia 1, 2

• Melatonin receptor agonist:

  • Ramelteon: 8 mg for sleep onset insomnia 2, 7

Second-Line Pharmacological Options

• Sedating antidepressants (especially when comorbid depression/anxiety exists):

  • Doxepin (3-6 mg): particularly effective for sleep maintenance insomnia 2, 4
  • Trazodone, amitriptyline, mirtazapine: may be considered, though evidence is less robust 1, 4

• Combination therapy:

  • BzRA or ramelteon plus sedating antidepressant 1

• Orexin receptor antagonists:

  • Suvorexant: effective for sleep maintenance insomnia 2, 8
  • Daridorexant: newer agent with 8-hour half-life and demonstrated long-term efficacy 8

Third-Line Options

• Other sedating agents (primarily for patients with comorbid conditions):
  • Anti-epilepsy medications (gabapentin, tiagabine) 1
  • Atypical antipsychotics (quetiapine, olanzapine) 1, 9

Medications Not Recommended

• Over-the-counter antihistamines or antihistamine/analgesic combinations due to lack of efficacy and safety data 1, 2
• Herbal and nutritional substances (e.g., valerian, melatonin) due to insufficient evidence 1, 2
• Older hypnotics including barbiturates, barbiturate-type drugs, and chloral hydrate 1, 2

Medication Selection Based on Symptom Pattern

• For sleep onset difficulty:
  • Zaleplon, ramelteon, zolpidem, or triazolam 2
• For sleep maintenance issues:
  • Eszopiclone, zolpidem, temazepam, doxepin, or suvorexant 2

Important Clinical Considerations

• Use medications at the lowest effective dose for the shortest duration possible (ideally ≤4-5 weeks) 3, 4
• Monitor patients regularly, especially during the initial treatment period 1, 2
• Be aware of potential adverse effects including:
  • Residual sedation and daytime impairment 4, 5
  • Memory and performance impairment 5
  • Risk of falls and injuries, particularly in older adults 4
  • Behavioral abnormalities including "sleep driving" 3, 5
• Provide patient education regarding treatment goals, safety concerns, potential side effects, and rebound insomnia 1

Special Populations

• Older adults:
  • Controlled-release melatonin and low-dose doxepin are recommended as first-line agents 9
  • Use lower doses of BzRAs (e.g., zolpidem 5 mg instead of 10 mg) 2, 5
• Patients with substance use history:
  • Avoid benzodiazepines due to high abuse potential 4
  • Consider ramelteon or orexin receptor antagonists which have little to no abuse potential 8
• Patients with sleep apnea or chronic lung disease:
  • Evaluation by a sleep specialist before prescribing sedating medications 9