What is the safest first‑line sleep aid for a 72‑year‑old man who recently underwent cardiac surgery and has anxiety?

Best Sleep Aid for a 72-Year-Old Male Post-Cardiac Surgery with Anxiety

Melatonin 3–5 mg administered 1–2 hours before bedtime is the safest first-line sleep aid for this patient, based on its proven safety profile in the perioperative cardiac surgery population, anxiolytic properties comparable to midazolam, and potential to reduce postoperative delirium. 1

Rationale for Melatonin as First-Line

• The Society for Perioperative Assessment and Quality Improvement (SPAQI) explicitly recommends continuing melatonin perioperatively, stating that available evidence demonstrates it is safe in the perioperative period and may decrease delirium in hospitalized elderly patients. 1

• A Cochrane review concluded that preoperative melatonin reduces anxiety compared with placebo in adults and may be as effective as midazolam, directly addressing both the sleep and anxiety components in this patient. 1

• In a prospective trial of 500 cardiac surgery patients, prophylactic melatonin given the night before surgery significantly reduced postoperative delirium (8.4% vs 20.8%, p=0.001), a critical outcome for morbidity and mortality in elderly post-cardiac surgery patients. 1

• Optimal timing is 1–2 hours before bedtime (approximately 6 PM) to align with the natural circadian rhythm and maximize sleep-promoting effects while also helping with bedtime resistance common in hospitalized patients. 2

• Dosing should be 3–5 mg, as this range has demonstrated efficacy in elderly insomniacs with documented improvements in sleep latency and quality, particularly in those with low endogenous melatonin levels. 3

Why NOT Other Common Options

Benzodiazepines (e.g., Lorazepam, Temazepam)

• Benzodiazepines carry unacceptable risks in elderly post-cardiac surgery patients, including increased fall risk, cognitive impairment, respiratory depression, and potential for dependence—all of which worsen morbidity and mortality outcomes. 4

• The American Geriatrics Society recommends against benzodiazepines in older adults due to associations with dementia, fractures, and major injuries. 1

Trazodone

• The American Academy of Sleep Medicine explicitly recommends AGAINST trazodone for insomnia, as it provides only minimal, clinically insignificant improvements (≈10 minutes reduction in sleep latency) with adverse events occurring in 75% of older adults (headache 30%, somnolence 23%). 5, 4

• The American Heart Association guidelines do not recommend trazodone for cardiovascular patients, instead favoring CBT-I first, then mirtazapine or melatonin-receptor agonists when medication is required. 5

Z-Drugs (Zolpidem, Eszopiclone, Zaleplon)

• While effective for sleep, Z-drugs carry significant risks in elderly post-surgical patients, including complex sleep behaviors (sleep-driving, sleep-walking), falls, fractures, and next-day cognitive impairment. 6, 7, 8

• These agents should be reserved for second-line use when melatonin and non-pharmacologic approaches have failed. 4

Over-the-Counter Antihistamines (Diphenhydramine, Doxylamine)

• The American Academy of Sleep Medicine explicitly recommends against antihistamines due to lack of efficacy data, strong anticholinergic effects (confusion, urinary retention, falls), and tolerance development after only 3–4 days. 4

Second-Line Pharmacologic Options (If Melatonin Insufficient)

For Combined Anxiety and Insomnia

• Mirtazapine 7.5–15 mg at bedtime is the preferred second-line agent for post-cardiac surgery patients with co-existing anxiety and insomnia, as the American Heart Association notes it is safe in cardiovascular disease and promotes both appetite and sleep. 5

• Mirtazapine must be taken nightly on a scheduled basis (not PRN) due to its 20–40 hour half-life requiring several days to reach steady-state therapeutic levels. 4

For Sleep-Maintenance Insomnia

• Low-dose doxepin 3–6 mg reduces wake after sleep onset by 22–23 minutes, has minimal anticholinergic activity at hypnotic doses, and carries no abuse potential—making it appropriate for elderly cardiac patients. 5, 4

• Ramelteon 8 mg is a melatonin-receptor agonist with no cardiovascular risks, no abuse potential, and no withdrawal symptoms, suitable when endogenous melatonin supplementation alone is insufficient. 5, 4

For Sleep-Onset Insomnia (If Needed)

• Zolpidem 5 mg (reduced dose for ≥65 years) shortens sleep-onset latency by ≈25 minutes but must be used cautiously due to fall risk and cognitive impairment in elderly patients. 5, 4, 8

• Zaleplon 5 mg (reduced dose for elderly) has an ultra-short half-life producing minimal residual sedation, appropriate for middle-of-the-night awakenings when ≥4 hours remain before awakening. 5, 4, 7

Essential Non-Pharmacologic First-Line: CBT-I

• Cognitive Behavioral Therapy for Insomnia (CBT-I) should be initiated immediately alongside any medication, as it provides superior long-term efficacy with sustained benefits after medication discontinuation. 5, 4

• CBT-I incorporates stimulus control, sleep restriction, relaxation techniques, and cognitive restructuring, and can be delivered via individual therapy, telephone, web-based modules, or self-help formats—all demonstrating effectiveness. 5, 4

• The American Heart Association specifically mandates CBT-I before any pharmacologic intervention for cardiovascular patients with insomnia. 5

Environmental and Non-Pharmacologic Adjuncts

• Noise and light reduction strategies using earplugs and eyeshades improve sleep quality and reduce delirium in ICU patients, including those post-cardiac surgery. 1

• Application of earplugs (with or without eyeshades) on the first postoperative ICU night after cardiac surgery maintained sleep quality at preoperative levels and should be offered to all patients. 1

Monitoring and Safety

• Reassess after 1–2 weeks to evaluate sleep outcomes, daytime functioning, and adverse effects such as morning sedation, cognitive impairment, or cardiac symptoms. 5

• Use the lowest effective dose for the shortest necessary duration, with ongoing CBT-I to facilitate eventual tapering of medication. 5, 4

• Screen for and address underlying contributors to insomnia—such as postoperative pain, medication side effects (β-blockers, diuretics), and sleep-disordered breathing, which are common after cardiac surgery. 5

Special Cardiac Surgery Considerations

• Sertraline is the preferred SSRI for anxiety in post-cardiac surgery patients if a standing anxiolytic is needed, owing to its lower propensity for QTc prolongation compared with citalopram or escitalopram. 5

• Avoid combining multiple sedating agents (e.g., benzodiazepine + Z-drug + sedating antidepressant) as this markedly increases risk of respiratory depression, cognitive impairment, and falls. 5, 4

• Low-dose dexmedetomidine infusion (ICU setting only) from admission until 8 AM postoperative day one greatly reduced delirium risk (9% vs 23%, p<0.0001) and improved sleep quality in cardiac surgery patients, though this is not applicable for floor-level care. 1

Treatment Algorithm

1. Initiate melatonin 3–5 mg 1–2 hours before bedtime + start CBT-I immediately (stimulus control, sleep restriction, relaxation). 1, 5, 2, 3

2. Add environmental modifications: earplugs, eyeshades, noise/light reduction. 1

3. If insufficient after 1–2 weeks: Add mirtazapine 7.5–15 mg nightly (for combined anxiety/insomnia) OR low-dose doxepin 3–6 mg (for sleep maintenance) OR ramelteon 8 mg (for sleep onset). 5, 4

4. If still insufficient: Consider zolpidem 5 mg or zaleplon 5 mg (age-adjusted doses) for short-term use only, with close monitoring for falls and cognitive effects. 5, 4

5. Reassess every 1–2 weeks for efficacy, adverse effects, and taper medication as CBT-I effects consolidate. 5, 4

Common Pitfalls to Avoid

• Do not prescribe trazodone despite its common use—harms outweigh minimal benefits in this population. 5, 4

• Do not use benzodiazepines as first-line—reserve only for refractory cases with extreme caution due to fall risk, cognitive impairment, and dependence. 5, 4

• Do not use antihistamines (diphenhydramine)—they lack efficacy and cause anticholinergic toxicity in elderly patients. 4

• Do not combine multiple sedating agents—this exponentially increases respiratory depression and fall risk. 5, 4

• Do not prescribe hypnotics PRN—agents like mirtazapine require scheduled dosing to maintain therapeutic levels. 4

• Do not neglect CBT-I—medication alone provides inferior long-term outcomes compared to combined behavioral and pharmacologic approaches. 5, 4