What are the potential side effects of quetiapine (Seroquel)?

Side Effects of Quetiapine

Quetiapine causes significant metabolic complications including weight gain, hyperglycemia, and dyslipidemia, along with sedation and orthostatic hypotension, with these effects occurring in a dose-dependent manner across all dosing ranges including low doses. 1, 2

Common Side Effects

Metabolic Complications

• Weight gain is one of the most significant problems with quetiapine, occurring commonly in patients and increasing in a dose-dependent fashion 3, 1, 2
• Weight gain averages approximately 2.1 kg in short-term trials, with risk of clinically significant weight gain (≥7% from baseline) increasing with higher doses 4, 2
• Hyperglycemia can occur and may lead to ketoacidosis, coma, or death, particularly in patients with diabetes or risk factors such as obesity or family history 1
• Elevated cholesterol and triglycerides develop frequently, often asymptomatically, requiring regular monitoring 3, 1
• Dose-dependent increases in total cholesterol, LDL cholesterol, and risk of hypertriglyceridemia and hypercholesterolemia occur even at low doses 2

Cardiovascular Effects

• Orthostatic hypotension occurs in 4-7% of patients, with elderly patients at particularly high risk 3
• Tachycardia may develop, with mean heart rate increases of 7 beats per minute compared to placebo 1
• QT prolongation has been reported, requiring ECG monitoring in high-risk patients 3
• Blood pressure increases can occur specifically in children and adolescents 1

Central Nervous System Effects

• Somnolence and sedation are extremely common, occurring in up to 57% of patients in bipolar depression trials 1
• Dizziness affects approximately 18% of patients 1
• In elderly patients, quetiapine significantly increases risk of cognitive decline and dementia (HR 7.1-8.1 compared to alternatives) 5
• Delirium can be induced by quetiapine, particularly in elderly patients, likely mediated through anticholinergic effects of the metabolite norquetiapine 6

Extrapyramidal Symptoms

• Extrapyramidal symptoms occur but are significantly less common than with typical antipsychotics 7, 3
• Tardive dyskinesia risk exists but is lower than with traditional antipsychotics; movements may not resolve even after discontinuation 3, 1
• Akathisia occurs in approximately 4% of patients 1

Other Common Effects

• Dry mouth (44% in bipolar depression trials) 1
• Constipation (10% in bipolar depression trials) 1
• Lethargy (5%) 1
• Increased appetite 1

Serious Adverse Effects

• Neuroleptic malignant syndrome is a potentially life-threatening complication 3
• Leukopenia and decreased white blood cell count, though rare 3, 1
• Seizures can occur 7, 1
• Hepatic transaminase elevations (particularly ALT), usually transient but requiring monitoring 3, 4
• Cataracts developed in animal studies, though not confirmed in humans; FDA recommends baseline and 6-month eye examinations 3

Post-Marketing Serious Reactions

• Anaphylactic reactions 1
• Cardiomyopathy and myocarditis 1
• Pancreatitis 1
• Rhabdomyolysis 1
• Stevens-Johnson syndrome and toxic epidermal necrolysis 1
• SIADH and hyponatremia 1
• Priapism 1

Special Population Risks

Elderly Patients

• Significantly increased mortality risk (HR 3.1 compared to trazodone) 5
• Markedly elevated dementia risk (HR 7.1-8.1 compared to alternatives) 5
• Increased fall risk (HR 2.8 compared to trazodone) 5
• Greater susceptibility to sedation, cognitive impairment, and orthostatic hypotension 3
• These risks persist even at low doses used for insomnia 5

Children and Adolescents

• Heart rate increases are more pronounced (mean increases of 11-13 bpm at higher doses) 1
• Blood pressure increases occur more commonly than in adults 1
• Tachycardia (>110 bpm) occurs in up to 8.5% at high doses 1

Dose-Dependent Effects

• Metabolic complications including weight gain and lipid abnormalities occur in a dose-dependent manner, but low doses are not safe 2
• Dyspepsia, abdominal pain, and weight gain show positive dose-response relationships 1
• Even low-dose quetiapine (<150 mg/day) causes clinically significant metabolic harm, emphasizing that minimal effective dosing reduces but does not eliminate risk 2

Thyroid and Hormonal Effects

• Small dose-related decreases in total and free thyroxine, usually reversible upon discontinuation 3, 4
• Prolactin increases may occur, though quetiapine generally does not elevate prolactin levels as much as other antipsychotics 3, 4
• Hypothyroidism reported in 2% of patients 1

Withdrawal Effects

• Insomnia, nausea, or vomiting can occur with sudden discontinuation 1
• Symptoms typically resolve within one week 1

Required Monitoring

• Baseline and regular monitoring of weight, glucose, and lipid profiles 3
• Baseline and periodic liver function tests 3
• Baseline and 6-month eye examinations per FDA recommendations 3
• ECG monitoring in patients with cardiovascular risk factors or on high doses 3
• Blood pressure monitoring, especially at initiation and dose increases 3
• Complete blood counts for leukopenia monitoring 1

Critical Prescribing Considerations

• The minimal effective dose should always be prescribed, as metabolic and cardiovascular effects are dose-dependent 2
• Low-dose quetiapine is not metabolically benign—prescriptions must be carefully justified and regularly reassessed 2
• Starting doses should be 25 mg/day in elderly patients and those with hepatic/renal impairment 4
• Avoid combination with benzodiazepines due to oversedation and respiratory depression risk 3
• In elderly patients, alternative agents like trazodone or mirtazapine have superior safety profiles 5