What are the pharmacotherapy options for insomnia?

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Last updated: March 9, 2025View editorial policy

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From the Guidelines

Pharmacotherapy for insomnia should begin with cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment, with medications added when necessary, as recommended by the American College of Physicians 1 and the American Academy of Sleep Medicine 1.

Key Considerations

  • The American College of Physicians recommends that clinicians use a shared decision-making approach to decide whether to add pharmacological therapy in adults with chronic insomnia disorder in whom CBT-I alone was unsuccessful 1.
  • The American Academy of Sleep Medicine clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults provides recommendations for the use of pharmacotherapy in the management of chronic insomnia, including the use of non-benzodiazepine hypnotics, benzodiazepines, and other medications 1.

Medication Options

  • For short-term insomnia, non-benzodiazepine hypnotics like zolpidem (5-10mg), eszopiclone (1-3mg), or zaleplon (5-20mg) taken 30 minutes before bedtime are recommended for 2-4 weeks.
  • For chronic insomnia, consider low-dose doxepin (3-6mg), ramelteon (8mg), or suvorexant (10-20mg).
  • Benzodiazepines like temazepam (15-30mg) or lorazepam (0.5-2mg) should be used cautiously due to dependence risk.
  • Trazodone (25-100mg) can be effective for insomnia with depression.

Important Considerations

  • All medications should be used at the lowest effective dose for the shortest duration possible.
  • Patients should be advised to maintain good sleep hygiene, avoid alcohol and caffeine before bedtime, and establish a regular sleep schedule.
  • These medications work through various mechanisms including enhancing GABA activity (benzodiazepines, non-benzodiazepines), blocking histamine receptors (doxepin), activating melatonin receptors (ramelteon), or blocking orexin receptors (suvorexant) to promote sleep onset and maintenance.
  • Regular reassessment is necessary to evaluate efficacy and monitor for side effects like daytime sedation, cognitive impairment, or dependence.

From the FDA Drug Label

Ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. Zolpidem is a GABA A receptor positive modulator presumed to exert its therapeutic effects in the short-term treatment of insomnia through binding to the benzodiazepine site of α1 subunit containing GABA A receptors, increasing the frequency of chloride channel opening resulting in the inhibition of neuronal excitation.

The pharmacotherapy options for insomnia include:

  • Ramelteon (PO): indicated for the treatment of insomnia characterized by difficulty with sleep onset 2, 2
  • Zolpidem (PO): a GABA A receptor positive modulator for the short-term treatment of insomnia 3

From the Research

Pharmacotherapy Options for Insomnia

The following pharmacotherapy options are available for the treatment of insomnia:

  • Benzodiazepines 4, 5
  • Benzodiazepine receptor agonists 4, 5
  • Daridorexant 4
  • Low-dose sedating antidepressants 4, 6
  • Orexin receptor antagonists 4
  • Prolonged-release melatonin 4
  • Melatonergic drugs such as ramelteon and agomelatine 7

Recommended Treatment Duration

The recommended treatment duration for these pharmacotherapy options varies:

  • Benzodiazepines, benzodiazepine receptor agonists, daridorexant, and low-dose sedating antidepressants: short-term treatment (≤ 4 weeks) 4
  • Orexin receptor antagonists: up to 3 months or longer in some cases 4
  • Prolonged-release melatonin: up to 3 months in patients ≥ 55 years 4

Non-Recommended Treatments

The following treatments are not recommended for insomnia:

  • Antihistaminergic drugs 4
  • Antipsychotics 4
  • Fast-release melatonin 4
  • Ramelteon 4 (contradictory to 7)
  • Phytotherapeutics 4

Considerations for Treatment

When choosing a pharmacotherapy option, considerations should include:

  • The segment of sleep that is disturbed 6
  • The presence of co-morbid illnesses 6
  • The potential for dependence and abuse 5, 8
  • The risk of sleep-related complex behaviors, such as sleep-driving 8, 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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