What are the effects of Seroquel (quetiapine)?

Seroquel (Quetiapine) Effects

Seroquel (quetiapine) is an atypical antipsychotic that effectively treats psychotic symptoms, agitation, and mood disorders, but carries significant risks including sedation, metabolic disturbances (weight gain, hyperglycemia, dyslipidemia), orthostatic hypotension, and tachycardia that require careful monitoring.

Therapeutic Effects

Psychiatric Indications and Efficacy

• Quetiapine is indicated for schizophrenia, bipolar disorder (including bipolar depression and mania), and agitation in dementia patients 1, 2, 3
• The drug demonstrates efficacy against both positive symptoms (hallucinations, delusions) and negative symptoms (emotional withdrawal, apathy) of schizophrenia 3, 4
• For bipolar depression, quetiapine 300-600 mg/day produces significantly greater improvements than placebo in depressive symptoms, with no difference in outcomes between the two dosages 2
• In dementia-related agitation, quetiapine is more sedating than other atypical antipsychotics, with dosing starting at 12.5 mg twice daily up to 200 mg twice daily 1

Mechanism of Action

• Quetiapine acts as an antagonist at both serotonin 5-HT2 and dopamine D2 receptors, with higher affinity for serotonin receptors 2, 4
• The antidepressant effects may relate to its metabolite norquetiapine, which inhibits noradrenaline reuptake 2
• The drug shows selectivity for mesolimbic and mesocortical dopamine systems (therapeutic areas) while minimally affecting nigrostriatal pathways (motor side effects) 4

Adverse Effects Profile

Common Side Effects

The most frequently reported adverse effects include: 5, 3

• Sedation and somnolence (most prominent effect)
• Dry mouth
• Constipation
• Dizziness
• Orthostatic hypotension
• Increased appetite and weight gain
• Tachycardia

Serious Metabolic Effects

Metabolic disturbances represent major concerns with quetiapine therapy: 5, 2

• Hyperglycemia and diabetes risk: Extremely high blood sugar can lead to ketoacidosis, coma, or death; patients should be monitored for excessive thirst, frequent urination, weakness, or fruity breath 5
• Dyslipidemia: Elevated cholesterol and triglycerides occur commonly, requiring lipid monitoring during treatment 5
• Weight gain: This is common and requires regular weight monitoring with dietary counseling 5, 6
  • However, long-term data suggest quetiapine may have a "weight-neutral" or normalizing effect, particularly beneficial in underweight or severely obese patients 6

Cardiovascular Effects

Quetiapine causes multiple cardiovascular effects requiring monitoring: 1, 5

• Orthostatic hypotension: Particularly problematic with initial dosing; patients should be warned about lightheadedness when rising 1, 5
• Tachycardia: Heart rate increases of 7 beats per minute on average in adults 5
• In children and adolescents, blood pressure increases occur and require monitoring before and during therapy 5
• QT prolongation has been reported, particularly in overdose situations 5

Neurological Effects

Quetiapine has a favorable extrapyramidal symptom (EPS) profile compared to typical antipsychotics: 1, 3, 4

• Placebo-level incidence of EPS across the entire dose range 3, 4
• Tardive dyskinesia risk exists but is lower than with typical antipsychotics 5
• Seizure risk is present, particularly at higher doses 5
• Cognitive effects may include sedation and cognitive blunting, though schizophrenia itself profoundly impacts cognition 1

Other Significant Adverse Effects

• Cataracts: Baseline and 6-month eye examinations are recommended 1, 5
• Low white blood cell count: Monitoring is prudent, though agranulocytosis is primarily associated with clozapine 1
• Elevated prolactin levels: May occur, requiring monitoring 5
• Hepatotoxicity: Transient liver enzyme elevations can occur 1
• Hypothyroidism: Thyroid function testing is recommended 5

Dosing Considerations

Adult Dosing

• For schizophrenia and agitation in dementia: Start 12.5-25 mg twice daily, titrate to 200-400 mg/day in divided doses 1
• For bipolar depression: 300-600 mg/day, with no efficacy difference between doses 2
• Dosing should be reduced in elderly patients and those with hepatic impairment 1

Pediatric Considerations

• In adolescents with schizophrenia, doses of 400-800 mg/day were studied, but higher doses (800 mg) caused more tachycardia and heart rate increases 5
• Children and adolescents require blood pressure monitoring before and during treatment 5

Critical Safety Warnings

Withdrawal Symptoms

Abrupt discontinuation causes withdrawal symptoms including: 5

• Insomnia or difficulty staying asleep
• Nausea and vomiting
• These symptoms typically resolve within one week 5

Overdose Management

In overdose situations: 5

• Death has been reported with overdoses as low as 13.6 grams
• Signs include exaggerated pharmacological effects: drowsiness, sedation, tachycardia, and hypotension
• QT prolongation may occur
• Do not use epinephrine or dopamine for hypotension, as beta-stimulation may worsen hypotension due to quetiapine's alpha-blockade 5
• Gastric lavage and activated charcoal should be considered
• No specific antidote exists; treatment is supportive 5

Monitoring Requirements

Essential monitoring parameters include: 5

• Blood glucose (baseline and periodic)
• Lipid panel (baseline and periodic)
• Weight (regular monitoring)
• Blood pressure and heart rate (especially in children/adolescents)
• Eye examinations (baseline and 6-month intervals)
• Thyroid function tests
• Complete blood count
• Liver function tests