What are the side effects of Seroquel (quetiapine)?

Side Effects of Seroquel (Quetiapine)

Quetiapine causes sedation, metabolic disturbances (weight gain, hyperglycemia, dyslipidemia), and orthostatic hypotension as its most clinically significant side effects, with lower risk of extrapyramidal symptoms compared to typical antipsychotics. 1, 2

Most Common Side Effects

Sedation and Central Nervous System Effects

• Somnolence/sedation is the most frequent side effect, occurring in up to 57% of patients in bipolar depression trials 2
• Drowsiness and dizziness (18% in bipolar depression) are particularly prominent during initial dose titration 3, 2
• These effects increase fall risk, especially in elderly patients 3
• Lethargy occurs in approximately 5% of patients 2

Anticholinergic Effects

• Dry mouth affects up to 44% of patients in bipolar depression studies 2
• Constipation occurs in approximately 10% of patients 2
• Dyspepsia and dysphagia have been reported 2

Metabolic Complications (Critical Monitoring Required)

Weight gain is one of the most significant problems with quetiapine, requiring regular monitoring 1:

• Dose-related weight gain demonstrated in clinical trials 2
• Weight increases of 4% or more observed in multiple studies 2
• May have "normalizing" effect in underweight or severely obese patients 4

Hyperglycemia and diabetes risk 1, 2:

• Can lead to diabetic ketoacidosis, coma, or death in extreme cases 2
• Baseline and periodic glucose monitoring mandatory, especially in patients with diabetes risk factors 1, 2
• Symptoms include excessive thirst, increased urination, hunger, weakness, and fruity breath odor 2

Dyslipidemia 1:

• Elevated cholesterol and triglycerides occur with long-term use 1
• Often asymptomatic, requiring laboratory monitoring 2

Cardiovascular Effects

Orthostatic hypotension is a significant concern 1, 2:

• Occurs in 4-7% of adult patients 1
• Manifests as lightheadedness, dizziness, or syncope upon standing 2
• Elderly patients have greater susceptibility 1
• Blood pressure monitoring essential when initiating or increasing doses 1

Cardiac conduction abnormalities 1, 3:

• QT prolongation reported, requiring caution in patients with cardiac conditions 1, 3
• Tachycardia occurs in approximately 1% of adults 2
• ECG monitoring recommended in patients with cardiovascular risk factors or high doses 1

Hypertension in pediatric populations 2:

• Blood pressure increases specifically noted in children and adolescents 2
• Baseline and ongoing monitoring required in young patients 2

Extrapyramidal Symptoms (Lower Risk Profile)

Quetiapine has significantly lower EPS risk than typical antipsychotics 1, 2:

• Extrapyramidal symptoms occur at placebo-level rates across most dose ranges 2
• Akathisia, tremor, and dystonia each occur in less than 4% of patients 2
• Risk increases at higher doses (600-750 mg/day) 2
• Anticholinergic medication use for EPS treatment similar to placebo (8-14% vs 14%) 2

Tardive dyskinesia risk exists but is lower than with typical antipsychotics 1, 2:

• Potentially irreversible even after discontinuation 2
• Manifests as involuntary movements of face, tongue, or other body parts 2

Serious but Rare Adverse Effects

Neuroleptic malignant syndrome is a potentially fatal complication 1, 3:

• Requires immediate recognition and intervention 1
• Presents with hyperthermia, muscle rigidity, altered mental status, and autonomic instability 2

Hematologic abnormalities 1:

• Leukopenia and decreased white blood cell count, though rare 1, 3
• Regular monitoring recommended 1

Hepatic effects 1:

• Elevations in transaminases may occur 1
• Baseline and periodic liver function tests advised 1

Ocular concerns 1:

• Cataract development observed in animal studies (not confirmed in humans) 1
• FDA recommends baseline and 6-month follow-up eye examinations 1

Additional Reported Side Effects

• Increased appetite (2-5% of patients) 2
• Nausea and vomiting (most common reason for discontinuation, 4-12.3% discontinuation rate) 1, 2
• Hypothyroidism and abnormal thyroid tests 2
• Increased prolactin levels (though less than typical antipsychotics) 2
• Seizures in susceptible individuals 2
• Hyperthermia 2

Post-Marketing Surveillance Reports

Serious adverse events identified after approval include 2:

• Anaphylactic reaction
• Cardiomyopathy and myocarditis
• Pancreatitis
• Rhabdomyolysis
• SIADH (syndrome of inappropriate antidiuretic hormone secretion)
• Stevens-Johnson syndrome and toxic epidermal necrolysis
• Retrograde amnesia
• Priapism

Special Population Considerations

Elderly patients require particular caution 1, 3:

• FDA black box warning against use in dementia-related psychosis due to increased mortality risk 3
• Higher risk of sedation and cognitive impairment 1
• Greater susceptibility to orthostatic hypotension 1
• Lower starting doses with gradual titration recommended 1, 3

Pediatric patients 2:

• Increased heart rate more common than in adults (up to 8.5% with tachycardia >110 bpm at 800 mg dose) 2
• Blood pressure increases specific to this population 2

Critical Monitoring Requirements

Mandatory baseline and ongoing assessments 1:

• Weight and BMI at each visit 1
• Fasting glucose and HbA1c (baseline, then periodically) 1
• Lipid panel (cholesterol and triglycerides) 1
• Liver function tests 1
• Blood pressure, especially during initiation and dose increases 1
• Eye examinations at baseline and 6 months 1
• ECG in patients with cardiovascular risk factors 1

Discontinuation Syndrome

Abrupt cessation can cause withdrawal symptoms 2:

• Insomnia or difficulty staying asleep 2
• Nausea and vomiting 2
• Symptoms typically resolve within one week 2

Risk Mitigation Strategies

Start low and titrate slowly 1, 3:

• Particularly important in elderly patients and those with hepatic impairment 1
• Reduces risk of orthostatic hypotension and sedation 3

Avoid dangerous drug combinations 5:

• Benzodiazepine combination increases risk of oversedation and respiratory depression 5

Implement lifestyle interventions early 2:

• Healthy, balanced diet and regular exercise to control weight gain 2
• Patient education about metabolic risks 2