A 48-year-old woman taking trazodone 100 mg at bedtime for insomnia continues to experience nocturnal awakenings; what management steps should be taken?

Management of Nocturnal Awakenings in a 48-Year-Old Woman on Trazodone 100 mg

Stop trazodone immediately and switch to low-dose doxepin 3–6 mg at bedtime, which is the preferred first-line pharmacologic agent for sleep-maintenance insomnia with proven efficacy and minimal side effects. 1

Why Trazodone Is Failing and Should Be Discontinued

• The American Academy of Sleep Medicine explicitly recommends against using trazodone for sleep-onset or sleep-maintenance insomnia because clinical trials show it produces only a ~10-minute reduction in sleep latency and ~8 minutes less wake after sleep onset, with no improvement in subjective sleep quality—harms outweigh the modest benefits. 1, 2

• Increasing the trazodone dose from 100 mg will amplify adverse effects (daytime drowsiness, dizziness, psychomotor impairment, cognitive deficits) without meaningful clinical benefit for nocturnal awakenings. 2, 3

• Trazodone at 100 mg causes measurable impairments in short-term memory, verbal learning, equilibrium, and arm muscle endurance that persist into the next day, making dose escalation counterproductive. 3

First-Line Pharmacologic Recommendation: Low-Dose Doxepin

• Doxepin 3–6 mg at bedtime is the preferred agent for sleep-maintenance insomnia, with moderate-quality evidence showing a 22–23 minute reduction in wake after sleep onset and improvements in sleep efficiency, total sleep time, and overall sleep quality. 1

• At hypnotic doses (3–6 mg), doxepin has minimal anticholinergic activity and no abuse potential, making it safer than benzodiazepine-receptor agonists and far superior to trazodone for middle-of-the-night awakenings. 1

• Start doxepin 3 mg at bedtime; if insufficient after 1–2 weeks, increase to 6 mg—this dose range maintains the favorable safety profile while providing additional efficacy. 1

Mandatory Concurrent Behavioral Therapy

• The American Academy of Sleep Medicine and the American College of Physicians issue a strong recommendation that all adults with chronic insomnia receive Cognitive Behavioral Therapy for Insomnia (CBT-I) as first-line treatment, either before or alongside any medication, because CBT-I provides superior long-term outcomes with sustained benefits after drug discontinuation. 4, 1

• Core CBT-I components that must be implemented include:

  • Stimulus control: Use the bed only for sleep; if unable to fall back asleep within ~20 minutes, leave the bed and engage in a relaxing activity until drowsy, then return. 4
  • Sleep restriction: Limit time in bed to approximate actual sleep time plus 30 minutes (minimum 5 hours), adjusting weekly based on sleep efficiency (total sleep time ÷ time in bed × 100%). 4
  • Cognitive restructuring: Address maladaptive beliefs such as "I can't sleep without medication" or "My life will be ruined if I can't sleep." 4
  • Relaxation training: Progressive muscle relaxation or breathing exercises to lower arousal states that interfere with sleep. 4

• CBT-I can be delivered via individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats show comparable effectiveness. 1

Alternative Second-Line Options (If Doxepin Fails or Is Contraindicated)

• Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes through a different mechanism than benzodiazepine-type agents, with a lower risk of cognitive and psychomotor impairment. 1

• Eszopiclone 2–3 mg (benzodiazepine-receptor agonist) increases total sleep time by 28–57 minutes and improves both sleep onset and maintenance, though it carries higher risks of complex sleep behaviors, falls, and cognitive impairment compared with doxepin. 1, 5

• Zolpidem 10 mg (5 mg if age ≥65 years) shortens sleep-onset latency by ~25 minutes and adds ~29 minutes to total sleep time, but is less specific for sleep-maintenance problems than doxepin. 1, 5

Critical Safety Monitoring

• Reassess after 1–2 weeks to evaluate changes in nocturnal awakenings, total sleep time, daytime functioning, and adverse effects such as morning sedation or cognitive impairment. 1

• Screen for complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating) at every visit; discontinue the medication immediately if such behaviors occur—all benzodiazepine-receptor agonists carry FDA warnings for these risks. 1

• If insomnia persists beyond 7–10 days despite appropriate treatment, evaluate for underlying sleep disorders such as obstructive sleep apnea, restless-legs syndrome, or periodic limb movement disorder, which require specific interventions. 1

Common Pitfalls to Avoid

• Do not increase trazodone to 150–200 mg in an attempt to improve sleep-maintenance—this will worsen daytime cognitive and motor impairments without addressing the nocturnal awakenings. 2, 3

• Do not add a second hypnotic (e.g., benzodiazepine or Z-drug) to trazodone—this creates dangerous polypharmacy with additive CNS depression, respiratory risk, falls, and cognitive impairment. 1

• Do not initiate doxepin without concurrent CBT-I, as behavioral therapy provides more durable benefits than medication alone and is mandated as first-line treatment by guideline societies. 4, 1

• Do not use over-the-counter antihistamines (diphenhydramine, doxylamine) as alternatives—they lack efficacy data, cause strong anticholinergic effects (confusion, urinary retention, falls), and develop tolerance within 3–4 days. 1