What are the potential side effects of quetiapine (antipsychotic medication) in patients, particularly the elderly or those with a history of cardiovascular disease?

Side Effects of Quetiapine

Quetiapine carries significant risks of sedation, orthostatic hypotension, dizziness, metabolic effects, and cardiovascular complications, with particularly heightened dangers in elderly patients and those with cardiovascular disease, where it should be used with extreme caution or avoided entirely. 1, 2

Common Side Effects

Cardiovascular Effects

• Orthostatic hypotension and dizziness are among the most prominent side effects, occurring especially during initial dose titration due to quetiapine's α1-adrenergic antagonist properties 1, 2
• Syncope occurs in approximately 1% of patients treated with quetiapine, which may lead to falls and injuries 2
• Tachycardia frequently accompanies hypotensive episodes 2, 3
• QT prolongation has been reported in overdose cases and when combined with other QT-prolonging medications, though it was not associated with persistent QT increases in standard clinical trials 2

Central Nervous System Effects

• Sedation is a hallmark effect of quetiapine, making it less likely to cause extrapyramidal symptoms (EPSEs) compared to other atypical antipsychotics 1
• Somnolence and drowsiness are common, contributing to fall risk 2
• Motor and sensory instability may occur, further increasing fall risk 2

Metabolic Effects

• Long-term use is associated with metabolic disturbances including weight gain, insulin resistance, and hypertriglyceridemia 1, 2
• Thyroid hormone alterations occur in a dose-related manner, with approximately 20% reduction in total and free T4 at higher therapeutic doses, typically maximal within the first six weeks 2
• TSH elevations occur in approximately 4.9% of patients, with some requiring thyroid replacement therapy 2

Hematologic Effects

• Leukopenia, neutropenia, and agranulocytosis have been reported, including fatal cases 2
• Patients with pre-existing low white blood cell counts or history of drug-induced leukopenia require frequent CBC monitoring during initial months of therapy 2
• Severe neutropenia (absolute neutrophil count <1000/mm³) mandates immediate discontinuation 2

Neurological Effects

• Seizures occur in approximately 0.5% of patients, compared to 0.2% on placebo 2
• Tardive dyskinesia can develop even after brief treatment periods at low doses, though the syndrome may remit partially or completely upon discontinuation 2
• Extrapyramidal symptoms are less common with quetiapine compared to other antipsychotics 1

Ophthalmologic Effects

• Cataract formation has been observed in chronic animal studies, and lens changes have been reported in humans during long-term treatment 2
• Slit lamp examination is recommended at treatment initiation and every 6 months during chronic therapy 2

High-Risk Populations

Elderly Patients

The elderly face dramatically elevated risks with quetiapine, particularly for mortality, dementia, cardiovascular events, and falls. 4, 5

• A 2025 study demonstrated that low-dose quetiapine for insomnia in older adults was associated with a 3.1-fold increased risk of mortality compared to trazodone (HR 3.1,95% CI 1.2-8.1) 4
• Risk of dementia was increased 8.1-fold compared to trazodone (HR 8.1,95% CI 4.1-15.8) and 7.1-fold compared to mirtazapine (HR 7.1,95% CI 3.5-14.4) 4
• Falls occurred 2.8 times more frequently compared to trazodone (HR 2.8,95% CI 1.4-5.3) 4
• Symptomatic bradycardia and hypotension can develop simultaneously in elderly patients with heart disease, particularly at higher doses 3
• Dose reduction is mandatory in older patients and those with hepatic impairment, with starting doses of 25 mg recommended 1

Patients with Cardiovascular Disease

Quetiapine should be used with particular caution in patients with known cardiovascular disease, including history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities. 2

• A 2022 nationwide study found that low-dose quetiapine use was associated with a 52% increased risk of major adverse cardiovascular events (aHR 1.52,95% CI 1.35-1.70) in as-treated analysis 5
• Cardiovascular death risk was increased 90% (aHR 1.90,95% CI 1.64-2.19) with continuous low-dose use 5
• Non-fatal ischemic stroke risk was elevated 37% (aHR 1.37,95% CI 1.13-1.68) 5
• Women and those aged ≥65 years face even greater cardiovascular risks, with hazard ratios of 1.28 and 1.24 respectively for major adverse cardiovascular events 5
• Patients with cerebrovascular disease or conditions predisposing to hypotension (dehydration, hypovolemia, antihypertensive medications) require heightened vigilance 2

Children and Adolescents

• Blood pressure increases are common in pediatric populations, with 15.2% experiencing systolic increases ≥20 mmHg and 40.6% experiencing diastolic increases ≥10 mmHg 2
• Blood pressure should be measured at baseline and periodically throughout treatment in this population 2

Drug Interactions and Contraindications

QT-Prolonging Medications

Quetiapine should be avoided in combination with other QT-prolonging drugs, including: 2

• Class 1A antiarrhythmics (quinidine, procainamide)
• Class III antiarrhythmics (amiodarone, sotalol)
• Other antipsychotics (ziprasidone, chlorpromazine, thioridazine)
• Certain antibiotics (gatifloxacin, moxifloxacin)
• Methadone and levomethadyl acetate

High-Risk Circumstances to Avoid

Quetiapine should be avoided in patients with: 2

• History of cardiac arrhythmias such as bradycardia
• Hypokalemia or hypomagnesemia
• Congenital QT prolongation
• Congestive heart failure or cardiac hypertrophy

Cytochrome P450 Interactions

• Quetiapine is metabolized by CYP3A4, requiring dose adjustments when co-administered with drugs affecting this isoenzyme 2, 6

Monitoring Requirements

Baseline Assessment

Before initiating quetiapine, obtain: 1

• BMI and waist circumference
• Blood pressure
• HbA1c and fasting glucose
• Lipid panel
• Prolactin level
• Liver function tests
• Urea and electrolytes
• Complete blood count
• Electrocardiogram

Ongoing Monitoring

• Fasting glucose should be rechecked 4 weeks after initiation 1
• BMI, waist circumference, and blood pressure should be checked weekly for 6 weeks 1
• All baseline measures should be repeated at 3 months and annually thereafter 1
• Both TSH and free T4 should be measured at baseline and follow-up, as TSH alone may not accurately reflect thyroid status 2
• Slit lamp examination at initiation and every 6 months during chronic treatment 2
• Patients with pre-existing low WBC require frequent CBC monitoring during the first few months 2

Critical Safety Considerations

Anticholinergic Burden

• Quetiapine has high central anticholinergic activity, which can worsen cognitive symptoms, particularly in elderly patients 1
• The anticholinergic burden should be reviewed and minimized when possible 1

Overdose Management

• Overdoses up to 30 grams have been reported with survival, though death has occurred with 13.6 grams 2
• QT prolongation is a particular concern in overdose situations 2
• Management includes airway protection, gastric lavage (if intubated), activated charcoal, and cardiovascular monitoring 2
• Epinephrine and dopamine should not be used for hypotension, as beta stimulation may worsen hypotension in the setting of quetiapine-induced alpha blockade 2

Common Pitfalls to Avoid

• Never use standard adult doses in elderly patients—always start at 25 mg and reduce doses in hepatic impairment 1
• Do not combine with benzodiazepines without extreme caution, as this increases risks of oversedation and respiratory depression 1
• Avoid using quetiapine off-label for insomnia in elderly patients, given the substantially increased mortality and dementia risks compared to safer alternatives like trazodone 4
• Do not rely on TSH alone for thyroid monitoring—always measure free T4 as well 2
• Minimize initial doses to 25 mg twice daily to reduce orthostatic hypotension and syncope risk, particularly during dose titration 2