What are the first-line medications for insomnia?

From the Guidelines

First-line medications for insomnia typically include low-dose doxepin (3-6mg), ramelteon (8mg), or non-benzodiazepine hypnotics like zolpidem (5-10mg), eszopiclone (1-3mg), and zaleplon (5-10mg). These medications should be taken 30 minutes before bedtime and used for short durations, ideally less than 2-4 weeks to prevent dependence, as suggested by the American Academy of Sleep Medicine clinical practice guideline 1.

Key Medications

• Low-dose doxepin works by blocking histamine receptors to promote sleep without significant next-day effects.
• Ramelteon targets melatonin receptors to help regulate sleep-wake cycles and is particularly useful for sleep onset issues.
• The "Z-drugs" (zolpidem, eszopiclone, zaleplon) enhance GABA activity in the brain, promoting sleep with fewer side effects than traditional benzodiazepines.

Important Considerations

• Before starting medication, patients should practice good sleep hygiene, including maintaining consistent sleep schedules, avoiding caffeine and electronics before bed, and creating a comfortable sleep environment.
• Elderly patients should start with half the standard dose due to increased sensitivity and risk of falls.
• These medications should be used alongside behavioral interventions like cognitive behavioral therapy for insomnia (CBT-I) for optimal results, as medications address symptoms while CBT-I treats underlying causes, as recommended by the American College of Physicians 1.

Behavioral Interventions

• Cognitive behavioral therapy for insomnia (CBT-I) should be considered first-line treatment for adults with chronic insomnia disorder, according to the American College of Physicians 1.
• CBT-I can be performed in primary care and has various delivery methods, including individual or group therapy, telephone- or Web-based modules, or self-help books.

From the FDA Drug Label

1 INDICATIONS AND USAGE BELSOMRA® (suvorexant) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

1. 1 Controlled Clinical Trials Chronic Insomnia Three randomized, doubleblind trials in subjects with chronic insomnia employing polysomnography (PSG) were provided as objective support of ramelteon's effectiveness in sleep initiation

The first-line medications for insomnia are not explicitly stated in the provided drug labels. However, based on the information provided, suvorexant and ramelteon are indicated for the treatment of insomnia.

• Suvorexant is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance 2.
• Ramelteon is effective in sleep initiation, as demonstrated by reduced latency to persistent sleep in clinical trials 3. It is essential to note that the FDA drug label does not provide a direct comparison or ranking of these medications as first-line treatments.

From the Research

First-Line Medications for Insomnia

The first-line medications for insomnia include non-benzodiazepine receptor agonists (non-BzRA) and cognitive-behavioral therapy.

• Non-BzRA are considered first-line agents for the short-term and long-term management of transient and chronic insomnia 4, 5.
• Cognitive-behavioral therapy is regarded as the first-line treatment for insomnia, with pharmacotherapy considered if it is not available or effective 6.
• Other medications such as benzodiazepines, melatonin receptor agonists, sedating antidepressants, antipsychotics, and antihistamines may also be used, but their use is often limited by concerns about side effects and dependence 5, 6, 7.

Non-Benzodiazepine Receptor Agonists

Non-benzodiazepine receptor agonists are a class of medications that have become the most commonly prescribed hypnotic agents for insomnia due to their proven efficacy, reduced side effects, and lower concern about addiction.

• Examples of non-benzodiazepine receptor agonists include zolpidem, zolpidem-controlled release, zaleplon, zopiclone, and eszopiclone 8.
• These medications are generally well-tolerated and have a favorable safety profile compared to older benzodiazepines and barbiturates 8.

Benzodiazepines

Benzodiazepines are also used to treat insomnia, but their use is often limited to short-term treatment due to concerns about dependence and misuse.

• Benzodiazepines are commonly used in Europe for the treatment of chronic insomnia, despite recommendations to limit their use to ≤4 weeks 7.
• Long-term use of benzodiazepines is associated with multiple consequences, including dependence and an increased risk of opioid use disorder 7.