What is the safest initial approach, including non‑pharmacologic and pharmacologic options, for treating insomnia in a 64‑year‑old man with acute flaccid myelitis, limited mobility, and depression who is tapering off ineffective trazodone?

Pharmacologic Management of Insomnia in a 64-Year-Old Male with Acute Flaccid Myelitis and Depression

Start low-dose doxepin 3 mg at bedtime immediately while simultaneously initiating Cognitive Behavioral Therapy for Insomnia (CBT-I), as this combination addresses both sleep maintenance and the underlying behavioral factors perpetuating insomnia in this immobilized, depressed patient. 1

Why Trazodone Failed and Should Not Be Continued

• The American Academy of Sleep Medicine explicitly recommends against trazodone for insomnia because the 50 mg dose produces only a clinically insignificant ~10-minute reduction in sleep latency, ~8 minutes less wake after sleep onset, and no improvement in subjective sleep quality—the very outcome this patient needs. 2

• At 50 mg, trazodone falls far below the therapeutic range (150–200 mg) required for meaningful sleep improvement; however, escalating the dose would expose him to unacceptable risks of orthostatic hypotension, cardiac arrhythmias, and priapism—particularly dangerous in an immobilized patient with limited mobility who cannot quickly respond to falls or cardiovascular events. 3, 4, 5

• Adverse events occur in ~75% of older adults on trazodone (headache 30%, somnolence 23%), and the harms outweigh the minimal benefits demonstrated in controlled trials. 2

First-Line Pharmacologic Choice: Low-Dose Doxepin

• Low-dose doxepin (3–6 mg) is the preferred first-line hypnotic for this patient because moderate-to-high quality evidence shows a 22–23 minute reduction in wake after sleep onset, improvements in sleep efficiency, total sleep time, and overall sleep quality—with adverse-event rates indistinguishable from placebo. 1, 6

• At hypnotic doses (3–6 mg), doxepin exhibits minimal anticholinergic activity and no abuse potential, making it especially suitable for a patient with recent neurologic injury who requires long-term sleep support without cognitive impairment or dependence risk. 1, 6

• Dosing algorithm:

  • Start doxepin 3 mg taken 30 minutes before bedtime. 1
  • Reassess sleep quality, total sleep time, and daytime functioning after 1–2 weeks. 1, 6
  • If response is inadequate, increase to 6 mg while preserving the favorable safety profile. 1, 6
  • Continue for up to 12 weeks or longer if effective; studies demonstrate sustained benefit without tolerance, dependence, or rebound insomnia after discontinuation. 1

Mandatory Concurrent Behavioral Therapy (CBT-I)

• Both the American Academy of Sleep Medicine and the American College of Physicians issue a strong recommendation that all adults with chronic insomnia receive CBT-I as the initial treatment, either before or alongside any medication, because CBT-I provides superior long-term efficacy and maintains benefits after drug discontinuation. 1, 6

• Core CBT-I components to implement immediately:

  • Stimulus control: Use the bed only for sleep; if unable to fall asleep within ~20 minutes, leave the bedroom and return only when sleepy; maintain consistent sleep-wake times even on weekends. 1, 6
  • Sleep restriction: Limit time in bed to match actual sleep time plus 30 minutes (calculate from a 1–2 week sleep diary); never prescribe less than 5 hours in bed. 1, 7
  • Cognitive restructuring: Address catastrophic thoughts about sleep loss and unrealistic expectations (e.g., "I must get 8 hours or I'll be disabled tomorrow"). 1, 6
  • Relaxation techniques: Progressive muscle relaxation, guided imagery, or diaphragmatic breathing before bedtime. 1, 7

• CBT-I can be delivered via individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats show comparable efficacy, making it feasible even for an immobilized patient. 1, 6

Addressing the Comorbid Depression

• The depression in this patient is situational (reactive to acute flaccid myelitis and immobility) and requires separate pharmacologic treatment beyond sleep management; doxepin at hypnotic doses (3–6 mg) does not provide antidepressant effects. 1, 6

• Start an SSRI or SNRI for depression concurrently with doxepin:

  • Sertraline 25–50 mg daily is effective and well-tolerated in adults with major depressive disorder, though it can cause insomnia as a side effect—monitor closely and adjust timing (morning dosing) if sleep worsens. 7
  • Mirtazapine 7.5–15 mg at bedtime is an alternative if you prefer a single agent that addresses both depression and sleep; however, it is positioned as a third-line option after benzodiazepine-receptor agonists have failed, and its sedating effects are paradoxically stronger at lower doses. 6

• Do not use trazodone as the antidepressant, as therapeutic doses (150–200 mg) required for depression carry unacceptable cardiovascular and fall risks in this immobilized patient. 3, 4, 5

Medications Explicitly Contraindicated in This Patient

• Benzodiazepines (lorazepam, temazepam, clonazepam) are absolutely contraindicated because they carry unacceptable risks of dependence, falls (catastrophic in an immobilized patient), cognitive impairment, respiratory depression, and associations with dementia and fractures. 1, 6, 7

• Over-the-counter antihistamines (diphenhydramine, doxylamine) must be avoided due to strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation, delirium) and rapid tolerance development within 3–4 days. 1, 6

• Antipsychotics (quetiapine, olanzapine) are not recommended despite widespread off-label use; evidence of benefit is weak, and they carry significant risks including weight gain, metabolic syndrome, extrapyramidal symptoms, and increased mortality in vulnerable populations. 1, 6

• Melatonin supplements produce only a ~9-minute reduction in sleep latency with insufficient supporting evidence for chronic insomnia. 1, 6

Monitoring and Reassessment Protocol

• Week 1–2: Reassess sleep-onset latency, total sleep time, nocturnal awakenings, and daytime functioning; screen for adverse effects (mild somnolence, headache, diarrhea—all rare at 3–6 mg). 1, 6

• Week 4: Document continued need for medication; if doxepin is effective, plan to continue for 3–6 months while maintaining CBT-I, then attempt a gradual taper. 1, 6

• If doxepin fails after 2 weeks at 6 mg, switch to a second-line agent:

  • Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes with a lower risk of cognitive impairment than benzodiazepine-type agents. 1, 6
  • Eszopiclone 2–3 mg improves both sleep onset and maintenance, increasing total sleep time by 28–57 minutes, but carries higher risks of complex sleep behaviors, falls, and cognitive impairment compared with doxepin. 1, 6

Common Pitfalls to Avoid

• Do not continue trazodone 50 mg or escalate the dose, as this violates explicit guideline recommendations and exposes the patient to cardiovascular and fall risks without meaningful sleep benefit. 2, 3, 4, 5

• Do not initiate doxepin without concurrent CBT-I, as this violates strong guideline recommendations and results in less durable benefit. 1, 6

• Do not add a benzodiazepine or Z-drug to doxepin, as combining multiple sedating agents markedly increases the risk of respiratory depression, falls, cognitive impairment, and complex sleep behaviors—especially dangerous in an immobilized patient. 1, 6

• Do not overlook the need for separate antidepressant therapy; hypnotic-dose doxepin does not treat major depression, and untreated depression will perpetuate insomnia. 1, 6, 7