What are the side effects of Seroquel (quetiapine)?

Side Effects of Seroquel (Quetiapine)

Quetiapine causes sedation, metabolic disturbances, and cardiovascular effects as its most clinically significant adverse reactions, with sedation being the most common reason patients discontinue the medication. 1, 2

Most Common Side Effects

In Adults

The most frequently reported adverse effects include:

• Sedation/somnolence (occurring in up to 57% of patients with bipolar depression) 2
• Dry mouth (44% in bipolar depression trials) 2
• Dizziness (18% in bipolar depression trials) 2
• Constipation (10% in bipolar depression trials) 2
• Orthostatic hypotension (4-7% of patients) 1, 2
• Headache, weakness, and abdominal pain 2

In Children and Adolescents

The most common side effects differ slightly from adults:

• Nausea 2
• Increased appetite 2
• Dry mouth 2
• Vomiting 2
• Weight gain 2
• Rapid heart rate 2

Serious Metabolic and Endocrine Effects

Weight Gain and Metabolic Syndrome

Weight gain is one of the most significant problems with quetiapine, occurring even at lower doses. 1, 2

• Mean weight gain of approximately 2.1 kg occurs in short-term trials 3
• Weight gain of 4% or more from baseline is common 2
• Metabolic effects include hyperglycemia and dyslipidemia, which can develop with long-term use 1, 2

Hyperglycemia and Diabetes Risk

Quetiapine can cause dangerous elevations in blood sugar:

• Extremely high blood sugar can lead to ketoacidosis, coma, or death 2
• Patients may experience excessive thirst, frequent urination, extreme hunger, weakness, or fruity-smelling breath 2
• Baseline and ongoing monitoring of glucose is mandatory 1, 2

Lipid Abnormalities

High cholesterol and triglyceride levels may occur without symptoms, requiring laboratory monitoring. 2

Cardiovascular Effects

Orthostatic Hypotension

• Occurs in 4-7% of adult patients 1
• Elderly patients have greater susceptibility to orthostatic hypotension 1
• Can cause lightheadedness or fainting when rising from sitting or lying positions 2
• Dose reduction is recommended in older patients to minimize this risk 1

Cardiac Conduction Effects

• QT prolongation has been reported 1
• Tachycardia occurs in approximately 1% of patients in schizophrenia trials 2
• Mean heart rate increases of 7 beats per minute compared to placebo 2
• In adolescents, heart rate increases are more pronounced (11-13 bpm increases with higher doses) 2

Blood Pressure Changes

• Children and adolescents may experience increases in blood pressure, requiring monitoring before and during treatment 2

Neurological Side Effects

Extrapyramidal Symptoms (EPS)

Quetiapine has a lower risk of EPS compared to typical antipsychotics, but they can still occur:

• EPS are less common than with traditional antipsychotics 1
• Risk increases at doses ≥2 mg/day (for risperidone comparison) 4
• Symptoms include muscle rigidity, tremor, and movement disorders 2

Tardive Dyskinesia

• Risk exists but is lower than with typical antipsychotics 1
• May be irreversible and can develop in 50% of elderly patients after 2 years of continuous typical antipsychotic use (quetiapine has lower risk) 4
• Involves uncontrollable movements of face, tongue, or other body parts 2
• May not resolve even after stopping quetiapine 2

Seizures

• Risk of seizures, particularly at higher doses 1
• Seizure risk appears elevated in youth, with documented cases in clinical trials 1

Cognitive Effects

• Elderly patients are at higher risk of sedation and cognitive impairment 1
• Quetiapine has high central anticholinergic activity, which may worsen cognitive symptoms 1

Hematologic Effects

Leukopenia and Neutropenia

• Low white blood cell count can occur 2
• Neutropenia risk may be higher in youth, with significant neutropenia developing in approximately 24% of patients in one study 1
• Agranulocytosis is rare but possible with any antipsychotic 5

Other Significant Adverse Effects

Hepatic Effects

• Elevations in hepatic transaminase levels may occur 1, 2
• Generally transient and asymptomatic 3
• Baseline and periodic liver function tests are advised 1

Ocular Effects

• Quetiapine was associated with cataract development in animal studies 1
• FDA recommends baseline and 6-month follow-up eye examinations 1

Thyroid Effects

• Abnormal thyroid tests may occur 2
• Small dose-related decreases in total and free thyroxine 3
• Usually reversible with treatment cessation 3

Prolactin Effects

• Increases in prolactin levels may occur, requiring monitoring 1
• However, quetiapine generally does not cause prolactin elevation compared to typical antipsychotics 3, 6

Neuroleptic Malignant Syndrome

• Rare but potentially fatal reaction 1
• Requires immediate medical attention 1

Withdrawal Effects

Abrupt discontinuation can cause withdrawal symptoms:

• Trouble sleeping or staying asleep (insomnia) 2
• Nausea 2
• Vomiting 2
• Symptoms usually improve within 1 week 2

Special Population Considerations

Elderly Patients

• Higher risk of sedation, cognitive impairment, and orthostatic hypotension 1
• Increased risk of death in elderly patients with dementia-related psychosis (FDA black box warning) 5
• Starting with lower doses is recommended 1

Pediatric Patients

• Higher risk of neutropenia and seizures compared to adults 1
• More pronounced cardiovascular effects (heart rate and blood pressure increases) 2

Critical Monitoring Requirements

Comprehensive baseline assessment must include:

• BMI, waist circumference, and blood pressure 1
• HbA1c and fasting glucose 1
• Lipid panel 1
• Complete blood count and prolactin level 1
• Liver function tests 1
• Eye examination 1
• ECG in patients with cardiovascular risk factors 1
• Documentation of any preexisting abnormal movements 1

Ongoing monitoring schedule:

• Weight and blood pressure: weekly for 6 weeks, then regularly 1
• Fasting glucose: at 4 weeks 1
• Comprehensive metabolic panel: at 3 months, then annually 1
• Eye examinations: at 6 months, then as indicated 1
• Blood pressure monitoring particularly when initiating or increasing doses 1

Post-Marketing Adverse Reactions

Additional serious reactions reported after market approval include:

• Anaphylactic reaction 2
• Cardiomyopathy and myocarditis 2
• Hyponatremia and SIADH 2
• Pancreatitis 2
• Rhabdomyolysis 2
• Stevens-Johnson syndrome and toxic epidermal necrolysis 2
• Retrograde amnesia 2
• Nocturnal enuresis 2

Clinical Pitfalls to Avoid

Do not combine quetiapine with benzodiazepines due to risk of oversedation and respiratory depression. 4

Do not use quetiapine for insomnia—major guidelines explicitly recommend against this off-label use due to serious adverse effects that outweigh any potential benefits. 5

Avoid in patients with baseline QT prolongation or those taking other QT-prolonging medications. 5