What medications are used to treat sleep maintenance insomnia?

Medications for Sleep Maintenance Insomnia

For sleep maintenance insomnia (difficulty staying asleep), use eszopiclone, zolpidem, doxepin, suvorexant, or temazepam as first-line pharmacologic options, with eszopiclone and doxepin having the strongest evidence specifically for maintaining sleep throughout the night. 1

First-Line Agents for Sleep Maintenance

Eszopiclone (Preferred Option)

• Eszopiclone 2-3 mg is specifically FDA-approved for both sleep onset AND sleep maintenance insomnia with no short-term usage restrictions 2
• The American Academy of Sleep Medicine recommends eszopiclone as a treatment for sleep maintenance insomnia based on trials of 2 mg and 3 mg doses 1
• Eszopiclone demonstrates consistent efficacy in reducing wake time after sleep onset and nocturnal awakenings in trials up to 6 months duration 3, 4
• Dose: 2-3 mg at bedtime for adults; 1-2 mg for elderly or debilitated patients 1, 2

Doxepin (Low-Dose)

• Low-dose doxepin 3-6 mg is particularly effective for sleep maintenance insomnia with minimal anticholinergic side effects at these doses 1
• The American Academy of Sleep Medicine recommends doxepin specifically for sleep maintenance insomnia 1
• This is distinct from higher antidepressant doses and has a favorable safety profile 1

Zolpidem

• Zolpidem 10 mg is recommended for both sleep onset and sleep maintenance insomnia 1
• Standard formulation: 10 mg at bedtime for adults; 5 mg for elderly, debilitated, or hepatic impairment 1
• Controlled-release formulation (12.5 mg) specifically designed for sleep maintenance 1

Suvorexant (Orexin Receptor Antagonist)

• The American Academy of Sleep Medicine suggests suvorexant specifically for sleep maintenance insomnia based on trials of 10,15/20, and 20 mg doses 1
• Represents a different mechanism of action (orexin receptor antagonism) compared to GABA-ergic agents 1

Temazepam

• Temazepam 15-30 mg is recommended for both sleep onset and sleep maintenance insomnia 1
• Dose: 15-30 mg at bedtime for adults; 7.5 mg for elderly or debilitated patients 1
• Short- to intermediate-acting benzodiazepine with established sleep maintenance efficacy 1

Agents NOT Recommended for Sleep Maintenance

Avoid These Medications

• Zaleplon is only effective for sleep onset, NOT sleep maintenance, due to its ultra-short half-life 1
• Triazolam is only recommended for sleep onset insomnia, not maintenance 1
• Ramelteon is only effective for sleep onset insomnia 1
• Trazodone should NOT be used for sleep maintenance insomnia despite its common off-label use 1
• Diphenhydramine, melatonin, valerian, and L-tryptophan are not recommended 1

Treatment Algorithm

Step 1: First-Line Pharmacotherapy

• Start with eszopiclone 2-3 mg OR doxepin 3-6 mg OR zolpidem 10 mg (or 12.5 mg controlled-release) 1
• These agents have the strongest evidence for sleep maintenance specifically 1

Step 2: Alternative First-Line Agent

• If initial agent fails or causes intolerable side effects, switch to a different first-line agent from above 1, 5
• Consider suvorexant or temazepam as alternatives 1

Step 3: Second-Line Options

• Consider sedating antidepressants at low doses (trazodone, mirtazapine, amitriptyline) only if first-line agents fail or if comorbid depression exists 1, 5
• Note: These have weaker evidence for primary insomnia 1

Critical Safety Considerations

Dosing and Administration

• Take medication only when able to remain in bed for 7-8 hours 2
• Do not take with or immediately after meals, as this delays absorption 2
• Use lowest effective dose and reassess need for continued treatment regularly 1, 5

Common Pitfalls to Avoid

• Do not use longer-acting benzodiazepines (flurazepam, lorazepam, clonazepam) due to risk of daytime sedation, falls, and cognitive impairment, especially in elderly 1, 5
• Avoid combining sleep medications with alcohol or other CNS depressants 2
• Be aware of complex sleep behaviors (sleep-walking, sleep-driving, sleep-eating) with all sedative-hypnotics 1, 2

Special Populations

• Elderly patients: Reduce doses by 50% (eszopiclone 1-2 mg, zolpidem 5 mg, temazepam 7.5 mg) 1, 2
• Hepatic impairment: Use reduced doses 1, 2
• Patients with substance use history: Exercise caution with all agents, though non-benzodiazepines may have lower abuse potential than traditional benzodiazepines 5

Side Effect Profiles

Eszopiclone

• Most common: unpleasant/metallic taste, dry mouth 2, 3
• Generally well-tolerated with no evidence of tolerance in 12-month trials 3, 4
• No rebound insomnia on discontinuation 4

Doxepin (Low-Dose)

• Minimal anticholinergic effects at 3-6 mg doses 1
• Less weight gain and cognitive impairment compared to higher doses 1

Benzodiazepines (Temazepam)

• Risk of tolerance, dependence, and withdrawal with prolonged use 5
• Potential for next-day sedation and cognitive impairment 1
• Higher fall risk in elderly compared to non-benzodiazepines 5

Duration of Treatment

• Eszopiclone is the only agent approved for long-term use without short-term restrictions 2, 6, 7
• Other agents traditionally limited to short-term use (2-4 weeks), though clinical practice often extends this 1
• Combine with cognitive-behavioral therapy for insomnia (CBT-I) when possible for sustained benefits 5