What medication is recommended for patients with middle insomnia (difficulty maintaining sleep) who can fall asleep easily but wake up in the middle of the night and can't go back to sleep?

Medications for Middle Insomnia (Sleep Maintenance Difficulty)

For patients with middle insomnia who can fall asleep easily but wake up in the middle of the night and can't go back to sleep, doxepin (3-6 mg) is the recommended first-line pharmacological treatment due to its specific efficacy for sleep maintenance insomnia with minimal side effects. 1

First-Line Medications for Sleep Maintenance Insomnia

• Doxepin (3-6 mg): Specifically recommended for sleep maintenance insomnia with demonstrated efficacy in reducing wake time after sleep onset by 22-23 minutes compared to placebo and increasing total sleep time by 26-32 minutes. 1

• Eszopiclone (2-3 mg): Effective for both sleep onset and maintenance insomnia, improving total sleep time by 28-57 minutes and reducing wake after sleep onset by 10-14 minutes compared to placebo. 1

• Suvorexant (10-20 mg): Orexin receptor antagonist specifically indicated for sleep maintenance insomnia, reducing wake after sleep onset by 16-28 minutes compared to placebo. 1

• Zolpidem (10 mg): Effective for both sleep onset and maintenance insomnia, improving total sleep time by 29 minutes and reducing wake after sleep onset by 25 minutes compared to placebo. 1

• Temazepam (15 mg): Benzodiazepine effective for both sleep onset and maintenance insomnia, with significant improvement in total sleep time (99 minutes longer than placebo). 1

Medication Selection Algorithm

1. First-line: Doxepin (3-6 mg) - specifically targets sleep maintenance with minimal side effects 1

2. Alternative options (if doxepin is ineffective or contraindicated):

   • Eszopiclone (2-3 mg) - particularly effective for long-term use with demonstrated efficacy in sleep maintenance 2, 3
   • Suvorexant (10-20 mg) - specifically targets sleep maintenance through orexin receptor antagonism 1
   • Zolpidem (10 mg) - effective but with potential for tolerance and dependence 1
   • Temazepam (15 mg) - effective but with higher risk of tolerance and dependence than non-benzodiazepines 1

Special Considerations

• Elderly patients: Reduce dosage (doxepin 3 mg, eszopiclone 1-2 mg) due to increased sensitivity to medications and risk of side effects. 4

• Patients with hepatic impairment: Eszopiclone should not exceed 2 mg in patients with severe hepatic impairment due to doubled systemic exposure. 4

• Medication timing: Hypnotics should be taken immediately before bedtime to avoid short-term memory impairment, hallucinations, impaired coordination, and dizziness. 4

• Duration of treatment: While most hypnotics are approved for short-term use, eszopiclone has been studied for longer periods (up to 6-12 months) without evidence of tolerance. 2, 3

Medications Not Recommended for Sleep Maintenance

• Trazodone: Not recommended for sleep maintenance insomnia based on clinical trials. 1

• Tiagabine: Not recommended for sleep maintenance insomnia. 1

• Over-the-counter options (diphenhydramine, melatonin, L-tryptophan, valerian): Not recommended for sleep maintenance insomnia due to lack of efficacy data. 1

Important Caveats and Pitfalls

• Evaluate for co-morbid conditions: Persistent insomnia not responding to 7-10 days of treatment may indicate an underlying psychiatric or medical condition. 4

• Risk of abnormal behaviors: Complex behaviors like sleep-driving may occur, especially with concomitant use of alcohol or other CNS depressants. 4

• Withdrawal effects: Rapid dose decrease or abrupt discontinuation may lead to withdrawal symptoms. Taper medications when discontinuing. 4

• Combine with behavioral therapy: Pharmacological treatment should be supplemented with cognitive-behavioral therapy for insomnia (CBT-I) when possible. 1

• Rebound insomnia: May occur after medication discontinuation, particularly with benzodiazepines. Non-benzodiazepines like eszopiclone have shown less rebound insomnia. 3, 5