What are the recommended medications for treating insomnia in patients, including those with a history of substance abuse or elderly patients?

Recommended Medications for Insomnia

For most adults with chronic insomnia, start with short/intermediate-acting benzodiazepine receptor agonists (BzRAs) such as eszopiclone 2-3 mg, zolpidem 10 mg, or zaleplon 10 mg as first-line pharmacotherapy, but only after initiating Cognitive Behavioral Therapy for Insomnia (CBT-I), which remains the standard of care. 1, 2

First-Line Treatment: CBT-I Before Medication

• CBT-I must be initiated before or alongside any pharmacotherapy for all adults with chronic insomnia, as it demonstrates superior long-term efficacy with sustained benefits after discontinuation compared to medications alone 2, 3
• CBT-I components include stimulus control therapy, sleep restriction therapy, relaxation techniques, and cognitive restructuring—deliverable through individual therapy, group sessions, telephone-based programs, or web-based modules 2, 3
• Sleep hygiene education alone is insufficient as monotherapy but should supplement other CBT-I components, including avoiding caffeine/alcohol in the evening, maintaining consistent sleep-wake times, and limiting daytime naps to 30 minutes before 2 PM 2

First-Line Pharmacotherapy Options

For Sleep Onset AND Maintenance Insomnia:

• Eszopiclone 2-3 mg: Recommended by the American Academy of Sleep Medicine for both sleep onset and maintenance, with moderate-quality evidence showing reduced sleep latency and wake after sleep onset 1, 4
• Zolpidem 10 mg (5 mg in elderly): Effective for both sleep initiation and maintenance, though carries increased risks in older adults including falls and cognitive impairment 1, 5, 6

For Sleep Onset Insomnia Only:

• Zaleplon 10 mg: Ultra-short half-life (~1 hour) makes it ideal for sleep initiation with minimal next-day sedation 1, 7
• Ramelteon 8 mg: Melatonin receptor agonist with zero addiction potential and no DEA scheduling—particularly suitable for patients with substance use history 1, 8, 2

For Sleep Maintenance Insomnia Only:

• Low-dose doxepin 3-6 mg: Highly effective for staying asleep with minimal anticholinergic effects at these doses and no weight gain 2, 9
• Suvorexant 10-20 mg: Orexin receptor antagonist reducing wake after sleep onset by 16-28 minutes 1, 2

Special Populations

Elderly Patients (≥65 years):

• First choice: Ramelteon 8 mg or low-dose doxepin 3 mg due to minimal fall risk and cognitive impairment 2, 9
• Zolpidem must be reduced to 5 mg maximum in elderly due to increased sensitivity and fall risk 9, 3
• Avoid long-acting benzodiazepines completely (lorazepam, temazepam) due to accumulation, prolonged half-life >24 hours, and significantly increased risk of falls, cognitive impairment, and respiratory depression 2, 9

Patients with Substance Use History:

• Ramelteon 8 mg is the only appropriate first-line choice as it is non-DEA scheduled with zero abuse potential 2, 3
• Avoid all benzodiazepines (temazepam, triazolam) which have significantly higher potential for tolerance, physical dependence, and severe withdrawal compared to non-benzodiazepines 2, 3
• Non-benzodiazepine hypnotics (zolpidem, eszopiclone, zaleplon) have lower but still present addiction potential—use with extreme caution 10, 11

Patients with Comorbid Depression/Anxiety:

• Sedating antidepressants are preferred initial choice as they simultaneously address both mood disorder and sleep disturbance 2, 3
• Options include low-dose doxepin 3-6 mg, mirtazapine, or trazodone (though trazodone is explicitly NOT recommended by AASM for primary insomnia due to lack of efficacy and fall risk) 1, 2, 3

Medications to AVOID

Explicitly NOT Recommended by AASM:

• Trazodone 50 mg: Despite widespread off-label use, AASM recommends AGAINST it for sleep onset or maintenance due to insufficient efficacy data and significant fall risk 1, 2, 9
• Over-the-counter antihistamines (diphenhydramine): Lack efficacy data, cause strong anticholinergic effects leading to confusion, urinary retention, fall risk in elderly, and daytime sedation 1, 2, 3
• Atypical antipsychotics (quetiapine, olanzapine): Explicitly warned against for primary insomnia due to weak evidence and significant metabolic side effects including weight gain and metabolic syndrome 2, 3
• Anticonvulsants (tiagabine, pregabalin): Not recommended for primary insomnia; only consider when other options have failed AND patient has comorbid condition requiring the medication 1, 2, 3

Critical Safety Considerations

Monitoring Requirements:

• Reassess after 7-10 days of treatment to evaluate efficacy on sleep latency, maintenance, and daytime functioning 2, 9
• Screen for complex sleep behaviors including sleep-walking, sleep-driving, and sleep-eating—all hypnotics carry FDA warnings for these risks 2, 4
• Regular follow-up every 2-4 weeks to assess for falls, cognitive impairment, morning sedation, and continued need for medication 9, 3

Dosing Principles:

• Use the lowest effective dose for the shortest duration possible—typically less than 4 weeks for acute insomnia 2, 3, 6
• Plan for medication tapering when conditions allow to prevent discontinuation symptoms 3
• Educate patients before prescribing about treatment goals, realistic expectations, safety concerns (especially morning driving impairment), and potential side effects 2, 3

Next-Day Impairment:

• Zolpidem 10 mg causes objectively measured psychomotor and memory impairment that persists 7.5-11.5 hours after dosing, even when patients subjectively feel alert 4, 5
• Eszopiclone 3 mg causes next-morning impairment with memory impairment reported in 1.3% vs 0% placebo 4
• Ramelteon does NOT impair next-day cognitive or motor performance, unlike benzodiazepines and Z-drugs 2

Common Pitfalls to Avoid

• Never use benzodiazepines as first-line treatment for primary insomnia—they have higher dependency risk, worse cognitive effects, and greater fall risk than non-benzodiazepines 2, 3
• Never prescribe hypnotics without implementing CBT-I, as behavioral interventions provide more sustained effects than medication alone 2, 3
• Never use standard adult doses in elderly patients—zolpidem requires reduction to 5 mg maximum, eszopiclone to 1-2 mg maximum 9, 3
• Never continue pharmacotherapy long-term without periodic reassessment of continued need and consideration of tapering 2, 3
• Never prescribe to patients who cannot get 7-8 hours of sleep before needing to be active, as this significantly increases risk of morning impairment and complex sleep behaviors 4