What are the treatment options for insomnia, including medications such as Hypnotics (e.g. Benzodiazepines) and Non-benzodiazepines (e.g. Zolpidem (Ambien))?

From the Guidelines

For the treatment of insomnia, cognitive behavioral therapy for insomnia (CBT-I) should be considered as the first-line treatment, and if pharmacologic therapy is necessary, low-dose doxepin or nonbenzodiazepine benzodiazepine receptor agonists (BZRAs) such as zolpidem, zaleplon, or eszopiclone may be offered at the lowest effective dose for the shortest duration possible. Insomnia medications can be categorized into prescription and over-the-counter options, each with its own set of benefits and risks. For occasional insomnia, over-the-counter options like diphenhydramine (Benadryl, ZzzQuil) or doxylamine (Unisom) at 25-50mg taken 30 minutes before bedtime can be effective for short-term use (less than two weeks) 1.

Prescription Medications for Insomnia

For persistent insomnia, prescription medications are more appropriate. These include:

• Benzodiazepines like temazepam (Restoril, 15-30mg)
• Non-benzodiazepine "Z-drugs" such as zolpidem (Ambien, 5-10mg), eszopiclone (Lunesta, 1-3mg), and zaleplon (Sonata, 5-10mg), all taken at bedtime
• Melatonin receptor agonists like ramelteon (Rozerem, 8mg)
• Orexin receptor antagonists such as suvorexant (Belsomra, 10-20mg)
• Sedating antidepressants like trazodone (50-100mg) 1.

Considerations for Treatment

It's crucial to use these medications at the lowest effective dose for the shortest duration possible, as many can cause dependence, morning grogginess, or rebound insomnia when stopped 1. The U.S. Food and Drug Administration has released safety announcements on the risk for serious injuries caused by sleep behaviors associated with nonbenzodiazepine BZRAs, emphasizing the need for cautious use 1. Always trying non-medication approaches first, including good sleep hygiene, cognitive behavioral therapy for insomnia, and addressing underlying conditions that may be causing sleep difficulties, is recommended 1.

From the FDA Drug Label

14.1 Transient Insomnia Normal adults experiencing transient insomnia (n=462) during the first night in a sleep laboratory were evaluated in a double-blind, parallel group, single-night trial comparing two doses of zolpidem (7. 5 and 10 mg) and placebo. 14. 2 Chronic Insomnia Zolpidem was evaluated in two controlled studies for the treatment of patients with chronic insomnia (most closely resembling primary insomnia, as defined in the APA Diagnostic and Statistical Manual of Mental Disorders, DSM-IV) 1 Controlled Substance Eszopiclone is a Schedule IV controlled substance under the Controlled Substances Act. 12.1 Mechanism of Action 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.

Insomnia Medications:

• Zolpidem: is used for the short-term treatment of insomnia, and it works by binding to the benzodiazepine site of α1 subunit containing GABA A receptors.
• Eszopiclone: is a Schedule IV controlled substance and is used for the treatment of insomnia. The choice of medication depends on the specific needs of the patient and the severity of their insomnia. 2, 3, 2

From the Research

Insomnia Medications

• Insomnia is a prevalent sleep problem associated with negative health-related outcomes and significant socioeconomic burden 4
• The most effective non-pharmacological treatment for chronic insomnia is cognitive-behavioral therapy for insomnia (CBT-i) 5
• CBT-i produces results that are equivalent to sleep medication, with no side effects, fewer episodes of relapse, and a tendency for sleep to continue to improve long past the end of treatment 5
• Digital cognitive-behavioral therapy application is being compared with zolpidem for the treatment of insomnia in an exploratory randomized controlled trial 6

Non-Pharmacological Approaches

• Non-pharmacological treatment for insomnia, especially cognitive behavioral therapy for insomnia (CBT-I), is effective in managing insomnia in a wide range of populations 4
• CBT-I is the first-line treatment for insomnia according to current treatment guidelines 7
• CBT-I is an effective treatment for patients with insomnia and a comorbid mental disorder, especially depression, PTSD, and alcohol dependency 7
• CBT-I is also an effective add-on treatment with the aim of improving mental health in patients with depression, PTSD, and symptom severity in outpatients with mixed diagnoses 7

Pharmacological Treatments

• Zolpidem tartrate is being compared with digital CBT in an exploratory randomized controlled trial for the treatment of insomnia 6
• Sleep medication has side effects and a higher risk of relapse compared to CBT-i 5
• Medication is frequently used to treat insomnia, especially in patients with mental disorders, despite CBT-I being the recommended first-line treatment 7