What are the treatment options for insomnia characterized by frequent nighttime awakenings?

Treatment of Insomnia with Frequent Nighttime Awakenings

Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for insomnia characterized by frequent nighttime awakenings, as it provides sustained improvements in wake after sleep onset (WASO) and is recommended as the standard of care before considering pharmacotherapy. 1, 2

Initial Treatment Approach: Psychological and Behavioral Therapy

CBT-I should be initiated as the primary intervention for all adults with chronic insomnia, including those with sleep maintenance problems. 1, 2 This recommendation is based on strong evidence showing that CBT-I produces clinically meaningful improvements sustained for up to 2 years, unlike pharmacotherapy which shows degradation of benefit after discontinuation. 2

Core Components of CBT-I for Nighttime Awakenings

• Stimulus control therapy is a standard treatment that strengthens the association between bed and sleep while extinguishing the conditioned arousal that occurs when patients spend excessive time awake in bed. 1, 3

• Sleep restriction therapy consolidates sleep by limiting time in bed to match actual sleep time, which increases homeostatic sleep drive and reduces nighttime awakenings. 1

• Cognitive therapy addresses distorted beliefs about sleep and reduces anxiety about nighttime awakenings, helping patients restructure maladaptive thoughts into more sleep-compatible attitudes. 1

• Relaxation training (including progressive muscle relaxation) reduces psychophysiological arousal that contributes to sleep maintenance difficulties. 1, 3

Treatment Goals for Sleep Maintenance Insomnia

The specific therapeutic target for nighttime awakenings is achieving WASO < 30 minutes and/or decreased frequency of awakenings. 1 Additional goals include total sleep time > 6 hours and sleep efficiency > 80-85%. 1

Pharmacological Treatment (Second-Line)

When CBT-I is insufficient after 2-4 weeks or unavailable, pharmacotherapy may be considered through shared decision-making. 4, 2

Preferred Medications for Sleep Maintenance Insomnia

For nighttime awakenings specifically, medications with longer half-lives that target sleep maintenance are preferred:

• Eszopiclone (2-3 mg) is suggested for both sleep onset and sleep maintenance insomnia, with demonstrated efficacy in reducing WASO in placebo-controlled trials. 1, 5 This agent has a relatively longer half-life compared to zaleplon or ramelteon and is more likely to improve sleep maintenance. 1

• Doxepin (3-6 mg) is specifically recommended for sleep maintenance insomnia through histamine H1 receptor antagonism, with evidence supporting its use for nighttime awakenings. 1, 4

• Suvorexant (10-20 mg), an orexin receptor antagonist, is suggested specifically for sleep maintenance insomnia and targets the mechanisms underlying nighttime awakenings. 1

• Temazepam (15 mg) is suggested for both sleep onset and sleep maintenance insomnia, with a longer half-life that addresses nighttime awakenings. 1

Medications to Avoid for Sleep Maintenance Problems

Critical pitfall: Zaleplon and ramelteon have very short half-lives and are unlikely to reduce WASO—they primarily affect sleep latency and should not be chosen for patients whose main complaint is nighttime awakenings. 1

Avoid antihistamines (including diphenhydramine) due to lack of efficacy data, anticholinergic properties, and safety concerns. 1, 4

Avoid trazodone, tiagabine, melatonin, L-tryptophan, and valerian as the American Academy of Sleep Medicine suggests clinicians not use these agents for sleep maintenance insomnia based on insufficient evidence. 1

Treatment Algorithm

1. Initiate CBT-I as first-line therapy, targeting stimulus control, sleep restriction, and cognitive restructuring. 1, 2

2. Monitor response using sleep diaries to track WASO and number of awakenings over 2-4 weeks. 1

3. If insufficient improvement after 2-4 weeks of CBT-I, continue behavioral therapy and add pharmacotherapy:

   • For isolated sleep maintenance problems: doxepin 3-6 mg or suvorexant 10-20 mg 1, 4
   • For combined sleep onset and maintenance problems: eszopiclone 2-3 mg or temazepam 15 mg 1

4. Reassess regularly for treatment efficacy, side effects, and potential tolerance development. 4

Important Caveats

Benzodiazepine risks: While temazepam is an option, benzodiazepines carry risks of residual sedation, memory impairment, falls, dependence, and drug interactions. 1 Short/intermediate-acting benzodiazepine receptor agonists (BzRAs) are preferred when pharmacotherapy is necessary. 1

Rebound insomnia: Following discontinuation of eszopiclone, mild rebound effects may occur on the first night, characterized by increased WASO and reduced sleep efficiency, but these typically resolve by the second night. 5

Next-morning impairment: Eszopiclone 3 mg can cause psychomotor and memory impairment that persists 7.5-11.5 hours after dosing, even when patients do not subjectively perceive sedation. 5 Patients must be counseled about driving safety the morning after use.

Withdrawal considerations: When discontinuing BzRAs after extended use, monitor for withdrawal-emergent anxiety and insomnia, which can occur as pharmacodynamic tolerance develops. 5