What are the pharmacological treatments for insomnia?

From the Guidelines

Insomnia can be effectively treated with both non-drug approaches and medications, with cognitive behavioral therapy for insomnia (CBT-I) being the first-line treatment, and medications such as eszopiclone, zolpidem, and suvorexant being effective for short-term use. 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.

Non-Pharmacological Treatments

• CBT-I is a standard of treatment and carries a significantly favorable benefit:risk ratio, and all patients with chronic insomnia should receive CBT-I as a primary intervention 1.
• Good sleep hygiene practices, including consistent sleep schedules, limiting screen time before bed, avoiding caffeine and alcohol, and creating a comfortable sleep environment, should be practiced alongside medication use.

Pharmacological Treatments

• Eszopiclone, zolpidem, and suvorexant may improve short-term global and sleep outcomes for adults with insomnia disorder, but the comparative effectiveness and long-term efficacy of pharmacotherapies for insomnia are not known 1.
• Short-acting benzodiazepine receptor agonists like zolpidem (Ambien) 5-10mg, eszopiclone (Lunesta) 1-3mg, or zaleplon (Sonata) 5-10mg are effective for sleep initiation, and should be used at the lowest effective dose for 2-4 weeks maximum to avoid dependence.
• For chronic insomnia, consider trazodone 25-100mg, mirtazapine 7.5-15mg, or low-dose doxepin 3-6mg, which may have fewer side effects for long-term use.
• Melatonin 1-5mg can help regulate sleep cycles, particularly in older adults or those with circadian rhythm disorders.

Important Considerations

• The FDA has approved pharmacologic therapy for short-term use (4 to 5 weeks), and patients should not continue using the drugs for extended periods 1.
• Evidence is insufficient to evaluate the balance of the benefits and harms of long-term use of pharmacologic treatments in adults with chronic insomnia disorder 1.
• The selection of a particular drug should rest on the evidence summarized, as well as additional patient-level factors, such as the optimal pharmacokinetic profile, assessments of benefits versus harms, and past treatment history 1.

From the FDA Drug Label

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... The mechanism of action of suvorexant in the treatment of insomnia is presumed to be through antagonism of orexin receptors. Ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset.

The pharmacological treatments for insomnia include:

• GABA A receptor positive modulators such as zolpidem 2
• Orexin receptor antagonists such as suvorexant 3
• Melatonin receptor agonists such as ramelteon 4

From the Research

Pharmacological Treatments for Insomnia

The following pharmacological treatments are available for insomnia:

• Benzodiazepines and hypnotic benzodiazepine receptor agonists, such as zolpidem and zaleplon 5, 6, 7, 8
• Melatonin and melatonin receptor agonists, which have been approved for the treatment of insomnia 5, 7, 9
• Sedating antidepressants, antipsychotics, and antihistamines, although these are not approved by the U.S. Food and Drug Administration for this indication and have side effects that are sometimes severe 5, 7
• Orexin receptor antagonists, such as suvorexant and lemborexant, which have been introduced as a new treatment option for insomnia 5, 9

Treatment Considerations

When considering pharmacological treatments for insomnia, the following factors should be taken into account:

• The recommended first-line treatment is cognitive behavioral therapy for insomnia (CBT-I), but pharmacotherapy can be considered if CBT-I is not available or effective 5, 6, 7, 9, 8
• The use of benzodiazepines and Z-drugs is only recommended for a short duration (≤4 weeks) due to the risk of tolerance, dependence, and misuse 6
• Long-term use of benzodiazepines is associated with multiple consequences, including dependence and an increased risk of opioid use disorder 6
• Newer generation nonbenzodiazepines and newer drugs active on targets other than the gamma-aminobutyric acid receptor are available, but clear treatment guidelines are needed 7, 9, 8