What is the drug class, uses, and side effects of Quetiapine (atypical antipsychotic)?

Quetiapine: Drug Class, Uses, and Side Effects

Drug Class

Quetiapine is an atypical (second-generation) antipsychotic that functions as an antagonist at both serotonin 5-HT2 and dopamine D2 receptors, with higher affinity for serotonergic receptors. 1, 2 The drug also affects multiple neurotransmitter systems including histamine H1, and adrenergic alpha1 and alpha2 receptors 3.

FDA-Approved Uses

Quetiapine is FDA-approved for three primary indications:

• Schizophrenia in adults and adolescents (13-17 years) 1, 4
• Bipolar disorder, including:
  • Acute manic episodes (monotherapy or adjunct to lithium/divalproex) 1, 4
  • Bipolar depression 1, 5
• Major depressive disorder as adjunctive therapy to antidepressants 6, 5

Effective Dosing

• For schizophrenia and bipolar mania, efficacy is demonstrated at doses ≥250 mg/day, with target dosing of 300-450 mg/day in adults 6, 7
• For bipolar depression, doses of 300 mg/day or 600 mg/day are effective, with no significant difference between these two doses 5
• Dosing should start at 25-50 mg/day and be titrated upward to minimize orthostatic hypotension and sedation 6, 7

Off-Label Uses

While quetiapine is used off-label for anxiety disorders and insomnia, major guidelines explicitly recommend against using quetiapine for insomnia due to serious adverse effects that outweigh potential benefits 6. There is preliminary evidence supporting use in generalized anxiety disorder and treatment-resistant depression 8.

Side Effects

Most Common Adverse Effects (>5% incidence)

The most frequently reported side effects in adults include:

• Dry mouth (44% in bipolar depression) 4
• Somnolence/sedation (57% in bipolar depression, 17.5% in schizophrenia) 4, 7
• Dizziness (18% in bipolar depression, 9.6% in schizophrenia) 4, 7
• Constipation (10% in bipolar depression) 4
• Headache (19.4% in schizophrenia trials) 7
• Weight gain (approximately 2.1 kg in short-term trials) 1, 4, 7

Serious Metabolic and Endocrine Effects

Weight gain and metabolic disturbances represent the most significant clinical concerns with quetiapine:

• Extreme weight gain can occur and is the most common significant problem with atypical antipsychotics 1, 2
• Hyperglycemia and diabetes mellitus, including diabetic ketoacidosis, coma, and death in extreme cases 4
• Dyslipidemia with elevated cholesterol and triglycerides 4
• Baseline and ongoing monitoring is mandatory: BMI, waist circumference, blood pressure, HbA1c, fasting glucose, and lipid panel at baseline, 4 weeks, 3 months, and annually thereafter 6, 9

Cardiovascular Effects

Cardiovascular monitoring is essential due to multiple potential complications:

• Orthostatic hypotension (4-7% of patients), particularly at treatment initiation 1, 9, 4
• Tachycardia, with mean heart rate increases of 7 bpm in adults 4
• QT prolongation has been reported, requiring caution in patients with cardiovascular risk factors 1, 6, 9
• In children and adolescents, blood pressure increases require monitoring before and during treatment 4

Neurological Effects

Quetiapine has a favorable extrapyramidal symptom profile compared to typical antipsychotics:

• Extrapyramidal symptoms (EPS) occur at rates similar to placebo and significantly less than haloperidol 1, 4, 7
• Tardive dyskinesia can occur and may not resolve even after discontinuation 1, 9, 4
• Neuroleptic malignant syndrome is a rare but potentially fatal complication 1, 9
• Seizures may occur, particularly at higher doses, with potentially elevated risk in youth 9

Hematologic Effects

While rare, serious blood disorders require vigilance:

• Agranulocytosis can occur with any antipsychotic, including quetiapine 1, 6
• Leukopenia and neutropenia have been reported, with potentially higher risk in youth 1, 9
• One case of precipitous drop in absolute neutrophil count and platelets occurred in a 12-year-old 1

Hepatic Effects

Liver function monitoring is recommended:

• Transient elevations in hepatic transaminases occur and often resolve with continued treatment 1, 7
• Baseline and periodic liver function tests are prudent, especially given reports of fatty infiltrates associated with obesity in adolescents 1

Ocular Effects

Eye examination protocols exist due to animal study findings:

• Cataracts developed in dogs during quetiapine studies 1, 2
• The FDA recommends baseline and 6-month follow-up eye examinations, though cataracts have not been reported in humans 1, 9

Special Population Considerations

Elderly patients require particular caution:

• Black box warning: Increased mortality in elderly patients with dementia-related psychosis 6
• Higher risk of sedation, cognitive impairment, and orthostatic hypotension 9
• Dose reduction is recommended, starting at 25 mg/day with slower titration 9, 7

Children and adolescents show distinct patterns:

• Greater heart rate increases (12.8-13.4 bpm at 400-600 mg/day) compared to adults 4
• Potentially higher risk of neutropenia and seizures compared to adults 9
• Common side effects include nausea, increased appetite, vomiting, and rapid heart rate 4

Withdrawal Effects

Abrupt discontinuation should be avoided:

• Insomnia, nausea, and vomiting can occur with sudden cessation 4
• Symptoms typically resolve within one week of onset 4

Cognitive Effects

Unlike typical antipsychotics, quetiapine may improve cognition:

• Benefits in fine motor function, memory, and executive function have been demonstrated in adults 1
• Fewer cognitive difficulties compared to traditional neuroleptics 1