What are the recommended medications for treating insomnia?

Recommended Medications for Insomnia

First-line pharmacotherapy for insomnia should be short-to-intermediate acting benzodiazepine receptor agonists (BzRAs) such as zolpidem 10 mg, eszopiclone 2-3 mg, zaleplon 10 mg, or temazepam 15 mg, or alternatively ramelteon 8 mg, with selection based on whether the primary complaint is sleep onset versus sleep maintenance. 1, 2

Medication Selection Algorithm

For Sleep Onset Insomnia

• Zaleplon 10 mg is specifically indicated for difficulty falling asleep due to its short duration of action 3, 1, 4
• Zolpidem 10 mg (5 mg in elderly) effectively treats sleep onset and can also address maintenance issues 1, 2, 5
• Ramelteon 8 mg works as a melatonin receptor agonist and is particularly appropriate when minimizing cognitive risk is a priority, as it does not affect GABA receptors 1, 2, 6
• Triazolam 0.25 mg (0.125 mg in elderly) is an option but carries risk of rebound anxiety and is not considered truly first-line 3, 1

For Sleep Maintenance Insomnia

• Eszopiclone 2-3 mg is highly effective for both sleep onset and maintenance with no short-term usage restriction 3, 1, 2, 7
• Zolpidem 10 mg or controlled-release formulation 12.5 mg (6.25 mg in elderly/debilitated) addresses both onset and maintenance 3, 1, 2
• Temazepam 15-30 mg (7.5 mg in elderly) is a traditional benzodiazepine option for maintenance issues 3, 1, 2
• Low-dose doxepin 3-6 mg is specifically recommended for sleep maintenance and represents a second-line option 1, 4

For Combined Sleep Onset and Maintenance

• Eszopiclone, zolpidem, or temazepam are all appropriate when both problems coexist 2

Second-Line Options

When First-Line BzRAs Fail

• Try an alternative agent from the same BzRA class before switching to other drug categories 3, 2
• Consider longer-acting hypnotics like estazolam 1-2 mg (0.5 mg in elderly) if wake after sleep onset (WASO) persists 3
• Avoid flurazepam due to its extended half-life and risk of residual daytime drowsiness 3

Sedating Antidepressants

• Reserve for patients with comorbid depression or anxiety, or after other treatment failures 3, 1, 2
• Options include trazodone, mirtazapine, doxepin (higher doses), amitriptyline, and trimipramine 3, 2
• Important caveat: Evidence for efficacy when used alone is relatively weak, and no specific agent is superior to others in this class 3
• Trazodone has minimal anticholinergic activity compared to doxepin and amitriptyline 3
• Mirtazapine is associated with weight gain 3
• Note that low-dose sedating antidepressants do NOT constitute adequate treatment for major depression in patients with comorbid insomnia 3

Newer Agents

• Suvorexant (orexin receptor antagonist) is suggested for sleep maintenance insomnia 1

Medications NOT Recommended

Explicitly Avoid

• Over-the-counter antihistamines (diphenhydramine) due to lack of efficacy data, anticholinergic effects, and safety concerns including daytime sedation and delirium risk, especially in elderly patients 1, 2, 4
• Trazodone at 50 mg dose is specifically not recommended by current guidelines despite common clinical use 1, 4
• Herbal supplements (valerian) and nutritional substances (melatonin 2 mg) due to insufficient evidence of efficacy 1, 2, 4
• Barbiturates and chloral hydrate due to unacceptable safety profiles 1, 2, 4
• Tiagabine (anticonvulsant) and L-tryptophan lack sufficient benefit 1, 2, 4

Critical Safety Considerations

Cognitive and Behavioral Risks

• All BzRAs have been associated with reports of disruptive sleep-related behaviors including sleepwalking, eating, driving, and sexual behavior 3
• 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
• Zolpidem at doses of 10-20 mg has shown significant decrease in next-morning recall of information, indicating anterograde amnesia risk 5

Prescribing Principles

• Use the lowest effective dose for the shortest necessary duration 2, 4
• Caution patients about allowing appropriate sleep time, using only prescribed doses, and avoiding combination with alcohol 3
• Consider intermittent dosing (e.g., three nights per week) or as-needed use to reduce tolerance and dependence 2
• Follow patients regularly—every few weeks initially—to assess effectiveness, side effects, and ongoing need 2, 4

Dose Adjustments for Special Populations

• Elderly or debilitated patients require lower doses across all agents 3
• Hepatic impairment necessitates dose reduction for most BzRAs 3
• Eszopiclone maximum 2 mg in severe hepatic impairment 3
• Zaleplon 5 mg in mild-to-moderate hepatic impairment or with concomitant cimetidine 3

Integration with Non-Pharmacological Treatment

• Cognitive Behavioral Therapy for Insomnia (CBT-I) should be the initial treatment approach, with medication used as a supplement when necessary 1, 2, 4
• Short-term hypnotic treatment should be supplemented with behavioral and cognitive therapies when possible 3, 1, 2
• Tapering medication when conditions allow is recommended, with CBT-I facilitating successful discontinuation 2

Patient Education Requirements

• Educate all patients receiving pharmacotherapy about: treatment goals, realistic expectations, safety concerns, potential side effects (including complex sleep behaviors), drug interactions, availability of cognitive-behavioral treatments, risk of dosage escalation, and potential for rebound insomnia upon discontinuation 2

Common Pitfalls to Avoid

• Using benzodiazepines like lorazepam or clonazepam as first-line treatment—these are not specifically approved for insomnia and should be reserved for second or third-line use 1
• Prescribing sedating agents without considering their specific effects on sleep onset versus maintenance 1
• Continuing pharmacotherapy long-term without periodic reassessment 1, 2
• Failing to consider drug interactions and contraindications 1, 2
• Using medications with problematic side effect profiles in elderly patients, particularly those with anticholinergic effects 1, 2