What are the potential side effects of Seroquel (quetiapine) in older adults with a history of diabetes, high blood pressure, or heart disease?

Side Effects of Seroquel (Quetiapine) in Older Adults

Quetiapine carries significant risks in older adults with cardiovascular disease, diabetes, or hypertension, including increased mortality, orthostatic hypotension, metabolic disturbances, falls, and cognitive decline—particularly when used off-label for conditions like insomnia. 1, 2

Critical Safety Warnings

Black Box Warning: Increased Mortality

• Antipsychotics, including quetiapine, increase mortality risk in older adults with dementia-related psychosis 1
• The American Geriatrics Society Beers Criteria identifies antipsychotics as potentially inappropriate medications in older adults due to increased mortality risk 3
• A 2025 study found quetiapine associated with 3.1 times higher mortality risk compared to trazodone (HR 3.1,95% CI 1.2-8.1) when used for insomnia in older adults 2

Cardiovascular Risks in High-Risk Populations

Orthostatic Hypotension and Falls:

• Quetiapine induces orthostatic hypotension in 15-18% of older patients, particularly during initial dose titration, due to α1-adrenergic antagonist properties 1, 4, 5
• Postural hypotension, dizziness, and syncope may lead to falls and fractures 1
• Falls occurred at significantly higher rates: 2.8 times higher risk compared to trazodone (HR 2.8,95% CI 1.4-5.3) 2
• The combination of somnolence, postural hypotension, and motor instability creates substantial fall risk 1

Blood Pressure Considerations:

• In patients with hypertension on antihypertensive medications, quetiapine can exacerbate hypotension 1
• Should be used with particular caution in patients with known cardiovascular disease (myocardial infarction history, ischemic heart disease, heart failure, conduction abnormalities) 1
• Risk minimized by starting at 25 mg twice daily rather than higher doses 1

QT Prolongation:

• Quetiapine should be avoided in patients with cardiovascular disease, family history of QT prolongation, congestive heart failure, and heart hypertrophy 1
• Avoid combination with other QT-prolonging drugs (Class 1A/III antiarrhythmics, certain antibiotics) 1
• Particular caution in patients with cardiac arrhythmias, bradycardia, hypokalemia, or hypomagnesemia 1

Metabolic and Endocrine Effects in Diabetic Patients

Hyperglycemia and Diabetes:

• Quetiapine can cause hyperglycemia and may precipitate diabetic ketoacidosis or hyperosmolar coma 1
• Patients with diabetes require careful glucose monitoring when initiating quetiapine 1

Weight Gain:

• Weight gain occurs in 11-30% of older adults on quetiapine 5
• This is particularly problematic for patients with pre-existing diabetes or cardiovascular disease 5

Thyroid Effects:

• Dose-related decreases in thyroid hormone levels (approximately 20% reduction in T4) occur within first 6 weeks 1
• Both TSH and free T4 should be measured at baseline and follow-up, not TSH alone 1
• Some patients require thyroid replacement therapy 1

Neurological and Cognitive Side Effects

Cognitive Impairment:

• Quetiapine causes significantly greater cognitive impairment compared to placebo in older adults 5
• 8.1 times higher risk of new dementia diagnosis compared to trazodone (HR 8.1,95% CI 4.1-15.8) and 7.1 times higher compared to mirtazapine (HR 7.1,95% CI 3.5-14.4) 2

Extrapyramidal Symptoms (EPS):

• While quetiapine has lower EPS risk than typical antipsychotics, EPS-related adverse events still occur in 13% of older patients 4
• Quetiapine has moderate EPS risk—higher than quetiapine but lower than risperidone and typical antipsychotics 3

Tardive Dyskinesia:

• Risk increases with duration of treatment and total cumulative dose 1
• May be irreversible; drug discontinuation should be considered if signs appear 1
• Chronic treatment should use the smallest effective dose for the shortest duration 1

Seizures:

• Seizures occurred in 0.5% of patients in clinical trials 1
• Use cautiously in patients with seizure history or conditions lowering seizure threshold (common in those ≥65 years, including Alzheimer's dementia) 1

Common Side Effects

Most Frequently Reported (from clinical trials):

• Somnolence: 25-39% 5
• Dizziness: 15-27% 5
• Postural hypotension: 6-18% 5
• Headache: 10-23% 5

Additional Common Effects:

• Somnolence (31%), dizziness (17%), and postural hypotension (15%) were most common in 52-week elderly study 4
• Transient hypotension and somnolence may occur during initial titration 6

Hematologic Risks

Leukopenia and Agranulocytosis:

• Leukopenia/neutropenia reported with quetiapine, including fatal agranulocytosis cases 1
• Patients with pre-existing low WBC or history of drug-induced leukopenia require frequent CBC monitoring during first months 1
• Discontinue quetiapine if severe neutropenia develops (absolute neutrophil count <1000/mm³) 1

Special Considerations for Polypharmacy

Drug Interactions:

• Avoid combining quetiapine with benzodiazepines due to increased sedation risk 3
• Concurrent use of three or more CNS agents increases fall risk 3
• Increased bleeding risk when combined with anticoagulants (relevant for cardiovascular patients) 7
• Avoid with other QT-prolonging medications 1

Dosing Recommendations to Minimize Risk

Initial Dosing:

• Start at 25 mg twice daily to minimize orthostatic hypotension and syncope risk 1
• The American Geriatrics Society recommends significantly reduced starting doses compared to younger adults 3
• If hypotension occurs during titration, return to previous dose 1

Monitoring Requirements:

• Blood pressure monitoring (supine and standing) for orthostatic hypotension 7
• Complete fall risk assessment at initiation and recurrently during long-term therapy 1
• Glucose monitoring in diabetic patients 1
• TSH and free T4 at baseline and follow-up 1
• CBC monitoring in first months if risk factors for leukopenia 1
• Lens examination at initiation and 6-month intervals (cataract risk) 1

Clinical Context

Off-Label Use Concerns:

• Most quetiapine use in older adults (75%) is off-label 5
• The 2025 study specifically examined low-dose quetiapine for insomnia and found significantly increased mortality, dementia, and falls compared to safer alternatives 2
• Behavioral interventions should be tried before pharmacological treatment; if sedation needed for insomnia, consider alternatives with better safety profiles 3