Medications for Trouble Staying Asleep (Sleep Maintenance Insomnia)
For sleep maintenance insomnia, low-dose doxepin (3-6 mg) or suvorexant are the most strongly recommended first-line pharmacological options, with eszopiclone, zolpidem extended-release, and temazepam as effective alternatives. 1, 2
First-Line Pharmacotherapy for Sleep Maintenance
Low-dose doxepin (3-6 mg) is specifically recommended by the American Academy of Sleep Medicine for sleep maintenance insomnia, reducing wake after sleep onset by 22-23 minutes. 3, 1, 2 This works through histamine H1 receptor antagonism at low doses and has a favorable safety profile. 4
Suvorexant (10-20 mg), an orexin receptor antagonist, is recommended specifically for sleep maintenance insomnia, reducing wake time after sleep onset by 16-28 minutes and improving subjective total sleep time by 22.3-49.9 minutes. 1, 4, 2 This represents a completely different mechanism than traditional hypnotics. 1
Eszopiclone (2-3 mg) is suggested for both sleep onset and sleep maintenance insomnia by the American Academy of Sleep Medicine. 1
Zolpidem extended-release (10 mg, 5 mg in elderly) is recommended for sleep maintenance, with the extended-release formulation maintaining higher concentrations over more than 6 hours. 1, 5
Temazepam (15 mg), an intermediate-acting benzodiazepine, is suggested for both sleep onset and maintenance insomnia. 1, 4
Critical Dosing Considerations for Elderly Patients
In elderly patients, zolpidem must be reduced to 5 mg maximum due to increased risk of falls and cognitive impairment. 2 Doxepin should be initiated at 3 mg and not exceed 6 mg in this population. 2
Medications to Avoid for Sleep Maintenance
Trazodone is explicitly NOT recommended by the American Academy of Sleep Medicine for sleep maintenance insomnia despite its common off-label use, due to significant fall risk and lack of efficacy. 1, 4, 2
Over-the-counter antihistamines (diphenhydramine, etc.) are not recommended due to lack of efficacy data, safety concerns including daytime sedation and delirium (especially in older patients), and increased anticholinergic burden. 3, 1, 2
Antipsychotics should not be used as first-line due to problematic metabolic side effects including weight gain and metabolic dysfunction. 3, 4
Long-acting benzodiazepines (diazepam, clonazepam, lorazepam) carry increased risks without clear benefit, with half-lives longer than 24 hours leading to accumulation and impaired clearance in older patients and those with liver disease. 3
Herbal supplements (valerian) and melatonin are not recommended due to insufficient evidence of efficacy, with a phase III trial showing no effect of valerian on sleep quality. 3, 1
Treatment Duration and Safety Warnings
All hypnotics should be prescribed at the lowest effective dose for the shortest period possible, typically less than 4 weeks for acute insomnia. 3 The FDA warns that benzodiazepine and non-benzodiazepine hypnotics carry risks including daytime memory and psychomotor impairment, complex behaviors (sleep-driving), depression, suicidal thoughts, and associations with dementia (hazard ratio 2.34). 3, 1
If insomnia persists after 7-10 days of appropriate treatment, reevaluate for comorbid sleep disorders such as restless legs syndrome and obstructive sleep apnea. 1, 4
Essential Non-Pharmacological Component
Cognitive Behavioral Therapy for Insomnia (CBT-I) should be implemented alongside any pharmacotherapy as it has superior long-term efficacy compared to medications alone and is recommended as first-line treatment before considering medications. 1, 4, 2 Short-term hypnotic treatment must be supplemented with behavioral and cognitive therapies. 1
Common Pitfalls to Avoid
Do not use sedating agents without considering their specific effects on sleep maintenance versus sleep onset. 1 Zaleplon and ramelteon are primarily for sleep onset, not maintenance. 1
Do not combine multiple sedative medications, as this significantly increases risks including complex sleep behaviors, cognitive impairment, falls, and fractures, particularly in elderly patients. 1
Do not continue pharmacotherapy long-term without periodic reassessment every 2-4 weeks to assess effectiveness, side effects, and plan for medication tapering. 1, 2