What are the most recommended medications for insomnia?

Most Recommended Medications for Insomnia

For primary chronic insomnia, first-line pharmacological agents are short-intermediate acting benzodiazepine receptor agonists (zolpidem, eszopiclone, zaleplon, temazepam) or ramelteon, with the critical caveat that cognitive behavioral therapy for insomnia (CBT-I) should be the initial treatment approach whenever possible. 1, 2

Initial Treatment Framework

Behavioral therapy must come first. CBT-I is the gold standard initial intervention for chronic insomnia due to its durable long-term effects that persist after treatment discontinuation. 2 Medication should supplement—not replace—behavioral interventions when possible. 1

• Sleep hygiene alone is insufficient but should be combined with other therapies. 1, 2
• Stimulus control therapy, relaxation therapy, or multicomponent CBT-I are standard initial behavioral approaches. 1

First-Line Pharmacological Agents

When medication is necessary, the recommended sequence follows a clear hierarchy:

Primary Options (First-Line)

Benzodiazepine receptor agonists (BzRAs) or ramelteon are the initial pharmacological choices: 1

• Zolpidem 10 mg: Effective for both sleep onset and maintenance insomnia. 1, 3 FDA-approved with demonstrated superiority over placebo on sleep latency, duration, and efficiency. 3

• Eszopiclone 2-3 mg: Effective for both sleep onset and maintenance insomnia. 1 Recommended by the American Academy of Sleep Medicine. 1

• Zaleplon 10 mg: Specifically for sleep onset insomnia. 1 Shorter duration of action limits utility for maintenance issues. 1

• Temazepam 15 mg: Effective for both sleep onset and maintenance insomnia. 1 A traditional benzodiazepine option. 1

• Ramelteon 8 mg: Specifically for sleep onset insomnia. 1, 4 Works as a melatonin receptor agonist without affecting GABA receptors, offering minimal cognitive risk. 2, 4

Safest Options for Cognitive Preservation

If cognitive impairment is a concern (elderly patients, dementia risk), prioritize ramelteon or low-dose doxepin: 2

• Ramelteon 8 mg: No GABA receptor activity, avoiding amnesia and cognitive impairment risks associated with benzodiazepines. 2

• Low-dose doxepin 3-6 mg: Recommended specifically for sleep maintenance insomnia. 1, 2 Acts as a selective histamine H1 receptor antagonist at these doses without anticholinergic effects. 2, 5

Second-Line Options

If initial BzRAs or ramelteon fail, try an alternate agent from the same class before moving to other drug categories. 1

When Comorbid Depression/Anxiety Exists

Sedating antidepressants become appropriate when treating concurrent psychiatric conditions: 1

• Trazodone, amitriptyline, doxepin (higher doses), and mirtazapine are options. 1
• However, trazodone 50 mg is NOT recommended for primary insomnia based on insufficient efficacy data. 1, 2

Newer Agents

Suvorexant (orexin receptor antagonist): Recommended for sleep maintenance insomnia at 10,15/20, or 20 mg doses. 1 Represents a novel mechanism targeting the hypocretin/orexin system. 5, 6

Medications to AVOID

The following are explicitly NOT recommended: 1, 2

• Over-the-counter antihistamines (diphenhydramine): Anticholinergic effects worsen cognition, lack efficacy and safety data. 1, 2

• Melatonin 2 mg: Insufficient evidence for efficacy. 1, 2

• Valerian and herbal supplements: Lack of efficacy and safety data. 1

• Barbiturates and chloral hydrate: Outdated with unacceptable safety profiles. 1

• Tiagabine 4 mg: Not recommended due to insufficient benefit. 1

• L-tryptophan 250 mg: Not recommended. 1

Critical Safety Considerations

Cognitive Risks with Benzodiazepines and Z-Drugs

Benzodiazepines carry higher risk of amnesia, cognitive impairment, and potential contribution to dementia with long-term use. 2 Z-drugs (zolpidem, eszopiclone, zaleplon) also act on GABA receptors and carry cognitive side effect risks. 2

• Anterograde amnesia can occur, particularly with doses above 10 mg and when information is presented during peak drug effect (90 minutes post-dose). 3
• Next-day residual effects include decreased performance on cognitive testing. 3

Prescribing Principles

Use the lowest effective dose for the shortest necessary duration: 1, 2

• Follow patients every few weeks initially to assess effectiveness, side effects, and ongoing need. 1, 2
• Consider intermittent dosing (e.g., three nights per week) or as-needed use to reduce tolerance and dependence. 1, 2
• Taper medication when conditions allow; CBT-I facilitates successful discontinuation. 1
• Long-term use may be indicated for severe/refractory insomnia or chronic comorbid illness, but requires consistent follow-up. 1

Patient Education Requirements

All pharmacological treatment must include education about: 1

• Treatment goals and realistic expectations
• Safety concerns and potential side effects
• Drug interactions
• Availability of cognitive-behavioral treatments
• Risk of dosage escalation
• Potential for rebound insomnia upon discontinuation

Medication Selection Algorithm

Choose based on these factors in order of priority: 1

1. Symptom pattern: Sleep onset vs. maintenance insomnia
2. Cognitive risk: Elderly or dementia concerns favor ramelteon or low-dose doxepin
3. Comorbid conditions: Depression/anxiety may warrant sedating antidepressants
4. Past treatment responses
5. Contraindications and drug interactions
6. Patient preference and cost

Specific Recommendations by Symptom Pattern

For sleep onset insomnia: Zaleplon, zolpidem, ramelteon, or triazolam. 1

For sleep maintenance insomnia: Eszopiclone, zolpidem, temazepam, suvorexant, or low-dose doxepin. 1

For both onset and maintenance: Eszopiclone, zolpidem, or temazepam. 1