What are the best medications for insomnia?

Best Medications for Insomnia

Cognitive Behavioral Therapy for Insomnia (CBT-I) should be the initial treatment for all adults with chronic insomnia before any medication is prescribed, as it demonstrates superior long-term efficacy compared to all pharmacological options with minimal risk of adverse effects. 1, 2

When Pharmacotherapy Is Necessary

If CBT-I is insufficient, unavailable, or the patient cannot participate, medications should be added as a supplement—not a replacement—to behavioral interventions. 1, 2

First-Line Medication Options

The recommended sequence begins with short-intermediate acting benzodiazepine receptor agonists (BzRAs) or ramelteon: 3, 2

For Sleep Onset Difficulty:

• Zolpidem 10 mg (5 mg in elderly) - effective for both sleep onset and maintenance 2, 4
• Zaleplon 10 mg - specifically for sleep onset 2
• Ramelteon 8 mg - melatonin receptor agonist with no abuse potential, making it ideal for patients with substance use history 2, 5
• Triazolam 0.25 mg - though associated with rebound anxiety, not truly first-line 2

For Sleep Maintenance Difficulty:

• Eszopiclone 2-3 mg - effective for both onset and maintenance 2, 6
• Temazepam 15 mg - effective for both onset and maintenance 2
• Zolpidem 10 mg (5 mg in elderly) - also effective for maintenance 2

Second-Line Medication Options

If first-line BzRAs or ramelteon fail, consider: 3, 2

• Low-dose doxepin 3-6 mg - specifically for sleep maintenance insomnia with strong evidence 1, 2
• Suvorexant (orexin receptor antagonist) - for sleep maintenance, works through completely different mechanism than BzRAs 1, 2
• Sedating antidepressants (trazodone, amitriptyline, mirtazapine) - particularly when comorbid depression/anxiety exists 3, 2

Important caveat: Trazodone is specifically NOT recommended by the American Academy of Sleep Medicine despite widespread use. 2

Third-Line Options (Comorbid Conditions Only)

• Combined BzRA/ramelteon with sedating antidepressant 3
• Anti-epilepsy medications (gabapentin) - only suitable when patients may benefit from primary drug action 3
• Atypical antipsychotics (quetiapine, olanzapine) - NOT recommended as first-line due to problematic metabolic side effects 3, 1

Medications to Avoid

Never recommend these agents: 3, 2

• Over-the-counter antihistamines (diphenhydramine) - lack efficacy data and cause daytime sedation, delirium in elderly 3, 2
• Herbal supplements (valerian) and melatonin supplements - insufficient evidence of efficacy 3, 2
• Barbiturates and chloral hydrate - outdated with unacceptable safety profiles 3, 2
• Tiagabine - specifically not recommended by American Academy of Sleep Medicine 2

Critical Safety Considerations

All hypnotics carry significant risks that must be discussed with patients: 1

• Next-day impairment - psychomotor and memory impairment can persist 7.5-11.5 hours after dosing, even when patients don't perceive sedation 6
• Complex sleep behaviors - sleep-driving, sleep-walking 1
• Falls and fractures - particularly in elderly 1
• Cognitive impairment and potential dementia risk 1
• Dependence and withdrawal - especially with benzodiazepines 2

FDA approval is for short-term use only (4-5 weeks). 1 Medications should be prescribed at the lowest effective dose for the shortest duration possible. 1, 2

Special Population: Patients with Substance Use History

For patients with history of opioid or other substance abuse: 5

• Avoid all benzodiazepines due to high abuse potential and respiratory depression risk 5
• Ramelteon is the preferred medication due to lack of abuse potential 2, 5
• Suvorexant may be considered as alternative 2
• Low-dose doxepin for sleep maintenance 5
• CBT-I remains absolutely essential in this population 5

Treatment Algorithm

1. Implement CBT-I first - includes stimulus control, sleep restriction, cognitive therapy, sleep hygiene education 1, 2, 7

2. If CBT-I insufficient after adequate trial, add pharmacotherapy based on symptom pattern: 2

   • Sleep onset → zolpidem, zaleplon, or ramelteon
   • Sleep maintenance → eszopiclone, temazepam, doxepin, or suvorexant
   • Substance use history → ramelteon preferred

3. If first-line medication fails, try alternative agent in same class before moving to second-line 3, 2

4. Continue behavioral interventions even when using medications 3, 1

5. Monitor regularly - every few weeks initially for effectiveness, side effects, and need for ongoing medication 3

6. Taper when conditions allow - medication discontinuation is facilitated by concurrent CBT-I 3

Common Pitfalls to Avoid

• Starting with medication instead of CBT-I - violates evidence-based guidelines 1, 2
• Using long-acting benzodiazepines - increased risks without clear benefit 1
• Prescribing OTC antihistamines - lack efficacy data and problematic side effects 3, 2
• Failing to assess for underlying sleep disorders - sleep apnea, restless legs syndrome must be ruled out if insomnia persists beyond 7-10 days 2
• Combining multiple sedatives - significantly increases risk of falls, cognitive impairment, complex sleep behaviors 2
• Continuing long-term without reassessment - regular monitoring is essential 3, 2
• Ignoring patient's subjective perception of impairment - objective impairment can exist even when patient feels fine 6