What medications are used to treat insomnia?

Medications for Insomnia

First-Line Treatment: Cognitive Behavioral Therapy

Before any medication is prescribed, Cognitive Behavioral Therapy for Insomnia (CBT-I) should be offered as the initial treatment for chronic insomnia, as it demonstrates superior long-term outcomes with sustained benefits after discontinuation and fewer adverse effects compared to pharmacotherapy. 1, 2

First-Line Pharmacological Agents

When CBT-I fails or is unavailable, the American Academy of Sleep Medicine recommends short-to-intermediate acting benzodiazepine receptor agonists (BzRAs) or ramelteon as first-line medications 1, 2:

For Sleep-Onset Insomnia:

• Ramelteon 8 mg at bedtime carries zero addiction potential and is particularly suitable for patients with substance use history 1, 2, 3
• Zaleplon 10 mg has a very short half-life with minimal residual sedation 1, 2
• Zolpidem 10 mg (5 mg in elderly) is FDA-approved and effective for reducing sleep latency 2, 4

For Sleep-Maintenance Insomnia:

• Low-dose doxepin 3-6 mg is particularly effective with minimal side effects and no addiction potential 1, 2
• Eszopiclone 2-3 mg is FDA-approved for both sleep onset and maintenance, with demonstrated efficacy up to 6 months 2, 5, 6

For Both Onset and Maintenance:

• Eszopiclone 2-3 mg is the preferred choice as it addresses both components without developing rapid tolerance 2, 5, 6
• Zolpidem 10 mg (5 mg in elderly) is effective for both components 2, 4
• Temazepam 15 mg is a traditional benzodiazepine option, though carries higher risks than non-benzodiazepine alternatives 2

Second-Line Options

If initial BzRAs or ramelteon fail, try an alternate agent from the same class before moving to other drug categories 2:

• Sedating antidepressants (trazodone, amitriptyline, higher-dose doxepin, mirtazapine) become appropriate when treating concurrent depression or anxiety 1, 2
• These should be reserved for patients with comorbid psychiatric conditions that would benefit from their primary mechanism of action 1

Medications to Explicitly Avoid

The American Academy of Sleep Medicine explicitly recommends against 1, 2:

• Over-the-counter antihistamines (diphenhydramine) due to anticholinergic effects, lack of efficacy data, and safety concerns 2
• Melatonin supplements 2 mg due to insufficient evidence for efficacy 2
• Valerian and herbal supplements due to lack of efficacy and safety data 2
• Atypical antipsychotics (including olanzapine, quetiapine) for primary insomnia due to weak evidence and significant adverse effects 1
• Barbiturates and chloral hydrate due to unacceptable safety profiles 2

Special Population: Elderly Patients

For elderly patients, low-dose doxepin 3-6 mg is the most appropriate first choice for sleep maintenance insomnia, with ramelteon 8 mg preferred for sleep-onset difficulties. 7

Dose Adjustments for Elderly:

• Zolpidem: 5 mg (not 10 mg) 7
• Eszopiclone: 1-2 mg (not 3 mg) 7
• Zaleplon: 5 mg (not 10 mg) 7

Absolutely Avoid in Elderly:

• All benzodiazepines due to unacceptable risks of dependency, falls, cognitive impairment, respiratory depression, and increased dementia risk per American Geriatrics Society Beers Criteria 7
• Antihistamine-containing sleep aids due to strong anticholinergic effects 7
• Trazodone despite widespread off-label use, due to limited efficacy evidence 7

Critical Prescribing Principles

• Use the lowest effective dose for the shortest necessary duration with follow-up every few weeks initially to assess effectiveness and side effects 2
• Consider intermittent dosing (e.g., three nights per week) or as-needed use to reduce tolerance and dependence 2
• Combine with ongoing behavioral strategies rather than using medication in isolation 2, 7
• Taper medication when conditions allow, with CBT-I facilitating successful discontinuation 2
• Patient education is mandatory regarding treatment goals, realistic expectations, safety concerns, potential side effects, risk of dosage escalation, and potential for rebound insomnia upon discontinuation 2

Common Pitfalls to Avoid

• Do not use long-acting benzodiazepines (lorazepam) due to accumulation, active metabolites, and impaired clearance in elderly and hepatically impaired patients 1
• Do not prescribe traditional benzodiazepines when non-benzodiazepine alternatives exist, as they carry higher risks of tolerance, dependence, and severe withdrawal 1, 8
• Do not continue pharmacotherapy indefinitely without regular reassessment—long-term use should only be considered for severe/refractory insomnia with consistent follow-up 2
• Do not ignore the black box FDA warnings about serious injuries from complex sleep behaviors (sleepwalking, sleep driving) with BzRAs—counsel all patients on these risks 7