What are the best medications for treating insomnia?

Best Medications for Insomnia

For sleep onset insomnia, use zolpidem 10 mg, zaleplon 10 mg, ramelteon 8 mg, or triazolam 0.25 mg as first-line pharmacologic options; for sleep maintenance insomnia, use eszopiclone 2-3 mg, zolpidem 10 mg, temazepam 15 mg, or doxepin 3-6 mg. 1, 2

Critical First Step: Cognitive Behavioral Therapy

Before initiating any medication, cognitive behavioral therapy for insomnia (CBT-I) should be the initial intervention, as it represents the standard of care. 2 Sleep hygiene alone is insufficient but should be combined with other therapies. 1, 2

Pharmacologic Treatment Algorithm

For Sleep Onset Insomnia (Difficulty Falling Asleep)

First-line options include:

• Zaleplon 10 mg - ultra-short half-life, minimal residual sedation, no effect on sleep maintenance 1, 2
• Zolpidem 10 mg - effective for both sleep onset and maintenance, FDA-approved with extensive evidence 1, 3, 4
• Ramelteon 8 mg - melatonin receptor agonist, not DEA-scheduled, appropriate for patients with substance abuse history 1, 2, 5
• Triazolam 0.25 mg - benzodiazepine option but associated with rebound anxiety, not considered first-line 1

For Sleep Maintenance Insomnia (Difficulty Staying Asleep)

First-line options include:

• Eszopiclone 2-3 mg - longer half-life, improves sleep maintenance, FDA-approved for up to 6 months 1, 2, 4
• Zolpidem 10 mg - effective for both onset and maintenance 1, 3
• Temazepam 15 mg (7.5 mg for elderly/debilitated) - intermediate-acting benzodiazepine 1, 2
• Doxepin 3-6 mg - low-dose tricyclic antidepressant specifically for maintenance insomnia 1, 2
• Suvorexant 10-20 mg - orexin receptor antagonist for maintenance insomnia 1, 6

Second-Line and Alternative Agents

If initial agents fail, switch to an alternative within the same class based on the patient's response pattern. 1 If benzodiazepine receptor agonists are ineffective, consider sedating antidepressants, particularly when comorbid depression/anxiety exists (examples: trazodone, amitriptyline, mirtazapine). 1

For refractory cases, combined therapy with a benzodiazepine receptor agonist plus a sedating antidepressant may be appropriate. 1

Medications NOT Recommended

Avoid these agents for chronic insomnia:

• Trazodone 50 mg - despite widespread off-label use, the American Academy of Sleep Medicine explicitly recommends against it 1, 2
• Diphenhydramine and other OTC antihistamines - lack efficacy and safety data for chronic insomnia 1, 2
• Melatonin 2 mg, valerian, L-tryptophan - insufficient evidence 2
• Barbiturates and chloral hydrate - outdated with unfavorable safety profiles 1, 2
• Tiagabine 4 mg - anticonvulsant not recommended 1

Critical Prescribing Considerations

Medication selection should be guided by:

1. Symptom pattern (onset vs. maintenance)
2. Patient age (reduce doses in elderly: zolpidem 5 mg, temazepam 7.5 mg)
3. History of substance abuse (consider ramelteon, which is not DEA-scheduled)
4. Comorbid psychiatric conditions (sedating antidepressants may serve dual purpose)
5. Desired duration of action (zaleplon for ultra-short, eszopiclone for longer maintenance) 1

Common Pitfalls and Safety Concerns

Zolpidem-specific warnings: Associated with complex sleep behaviors (sleepwalking, sleep-driving), increased fall risk (OR 4.28), hip fractures (RR 1.92), and suicide risk (OR 2.08). 7 Women have higher plasma concentrations than men at 8 hours, requiring dose adjustment. 7 Rebound insomnia can occur with sleep onset latency increased by 13 minutes after discontinuation. 7

General precautions: All benzodiazepine receptor agonists carry risks of residual sedation, memory impairment, falls, and undesired sleep behaviors. 1 Withdrawal seizures have been reported with high-dose chronic zolpidem use (450-600 mg/day, but cases as low as 160 mg/day). 7

Monitoring and Long-Term Management

Follow patients every few weeks initially to assess effectiveness, side effects, and ongoing need for medication. 1, 2 Use the lowest effective maintenance dose and attempt tapering when conditions allow. 1 Medication tapering is facilitated by concurrent CBT-I. 1

Long-term prescribing (beyond 4 weeks) requires:

• Consistent follow-up and ongoing effectiveness assessment
• Monitoring for adverse effects
• Evaluation for new or worsening comorbid disorders
• Administration may be nightly, intermittent (3 nights/week), or as-needed 1

Chronic hypnotic medication may be indicated for severe/refractory insomnia or chronic comorbid illness, but patients should receive an adequate trial of CBT-I during long-term pharmacotherapy. 1