Is quetiapine (Seroquel) an appropriate sleep aid for patients recovering from cardiac surgery?

Quetiapine (Seroquel) Is Not Recommended as a Sleep Aid for Post-Cardiac Surgery Patients

Quetiapine should be avoided for insomnia in post-cardiac surgery patients due to significant cardiovascular risks, lack of efficacy data, and availability of safer alternatives with proven benefit in this population. 1, 2, 3

Why Quetiapine Is Inappropriate in This Population

Cardiovascular Safety Concerns

• The FDA label explicitly warns that quetiapine should be avoided in patients with cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure, and heart hypertrophy—all characteristics common in post-cardiac surgery patients. 3

• Quetiapine prolongs the QTc interval and should be avoided in combination with other QT-prolonging drugs (Class IA and III antiarrhythmics, certain antibiotics) frequently used in cardiac surgery patients. 3

• The drug should be avoided in patients with cardiac arrhythmias such as bradycardia, hypokalemia, or hypomagnesemia—electrolyte disturbances that are common postoperatively. 3

• A recent 2025 retrospective cohort study of 375 older adults receiving low-dose quetiapine for insomnia found significantly increased mortality (HR 3.1,95% CI 1.2-8.1), dementia (HR 8.1,95% CI 4.1-15.8), and falls (HR 2.8,95% CI 1.4-5.3) compared to trazodone. 4

Lack of Efficacy Evidence

• Quetiapine has been evaluated in only two clinical trials totaling 31 patients for insomnia without psychiatric comorbidity, with no active comparator trials (e.g., versus zolpidem) and minimal objective sleep testing. 5

• Current data do not support quetiapine as first-line treatment for sleep complications; it may only be considered in patients with psychiatric disorders (bipolar, schizophrenia) who fail primary treatments. 6

• Guidelines for insomnia treatment recommend quetiapine only in patients with specific comorbid psychiatric disorders, not for primary insomnia. 5

Observed Use Patterns in Cardiac Surgery

• In a 2025 study of 3,188 cardiac surgery patients, only 13.6% received antipsychotics postoperatively, with quetiapine being the most common (85% of antipsychotic use). 7

• Antipsychotic therapy was associated with discharge to a destination other than home (aRR 1.39,95% CI 1.11-1.66), suggesting worse functional outcomes. 7

• Only 12.4% of patients who received postoperative antipsychotics continued prescriptions at discharge, indicating these were short-term interventions for acute delirium rather than planned sleep management. 7

Evidence-Based Alternatives for Post-Cardiac Surgery Insomnia

First-Line: Melatonin

• The Society for Perioperative Assessment and Quality Improvement (SPAQI) explicitly recommends continuing melatonin perioperatively because it is safe and may lower delirium rates in hospitalized older adults. 1

• In a prospective trial of 500 cardiac surgery patients, prophylactic melatonin given the night before surgery reduced postoperative delirium (8.4% vs 20.8%; p = 0.001). 1

• Melatonin 3–5 mg at bedtime should be the first pharmacologic option given its proven safety and efficacy specifically in cardiac surgery patients. 1

Second-Line: Low-Dose Doxepin

• Low-dose doxepin 3–6 mg is the most appropriate medication for sleep-maintenance insomnia in older adults, with a favorable efficacy and safety profile recommended by the American College of Physicians. 2

• At 3–6 mg, doxepin acts solely as a selective histamine H₁-receptor antagonist, avoiding the anticholinergic, α-adrenergic, and cardiac-conduction effects seen at higher antidepressant doses. 2

• Multiple randomized controlled trials in elderly participants reported adverse-event rates indistinguishable from placebo, with no cardiac arrhythmias, QTc prolongation, or orthostatic hypotension. 2

Alternative Second-Line Options

• Ramelteon 8 mg carries no cardiovascular risk, no abuse potential, and no withdrawal symptoms, appropriate when endogenous melatonin alone is insufficient. 1

• Mirtazapine 7.5–15 mg at bedtime is the preferred second-line agent for combined anxiety and insomnia in post-cardiac surgery patients, per the American Heart Association, noting its cardiovascular safety. 1

Non-Pharmacologic Interventions (Mandatory)

• Cognitive Behavioral Therapy for Insomnia (CBT-I) should be initiated immediately alongside any medication, as it provides superior long-term efficacy and sustained benefits after drug discontinuation. 1

• Noise- and light-reduction strategies (earplugs, eye-shades) improve sleep quality and lower delirium rates in ICU patients, including those after cardiac surgery. 1

Medications to Explicitly Avoid

• Benzodiazepines should be avoided due to strong associations with dementia, fractures, major injuries, falls, cognitive impairment, and respiratory depression in older adults, per the American Geriatrics Society. 1, 2

• Trazodone is not recommended despite widespread off-label use; the American Academy of Sleep Medicine advises against it due to limited efficacy (≈10-minute reduction in sleep latency) and adverse events in ~75% of older patients. 1, 2

• Over-the-counter antihistamines (diphenhydramine, doxylamine) should be avoided due to lack of efficacy and pronounced anticholinergic side-effects (confusion, urinary retention, falls). 1, 2

Practical Management Algorithm

1. Implement CBT-I immediately (stimulus control, sleep restriction, relaxation techniques) with environmental modifications (earplugs, eye-shades). 1

2. Start melatonin 3–5 mg at bedtime as the first pharmacologic option. 1

3. If melatonin is insufficient after one week, add low-dose doxepin 3 mg for sleep-maintenance problems; increase to 6 mg after 1–2 weeks if needed. 2

4. For persistent sleep-onset difficulty, consider ramelteon 8 mg or mirtazapine 7.5–15 mg. 1

5. Reassess sleep outcomes, daytime functioning, and adverse effects after 1–2 weeks, with ongoing CBT-I to facilitate eventual medication tapering. 1

Common Pitfalls to Avoid

• Do not prescribe quetiapine based solely on its sedative properties without considering the cardiovascular contraindications and mortality risk in this population. 3, 4

• Do not use standard adult dosing in older adults; age-adjusted dosing is essential to reduce fall and cognitive-impairment risk. 2

• Do not combine multiple QT-prolonging medications in cardiac surgery patients with existing conduction abnormalities. 3

• Do not fail to implement CBT-I before or alongside pharmacotherapy, which forfeits the more durable benefits of behavioral therapy. 1