Makindo Medical Notes

💡 Key Safety Tip: Always perform an ECG and calculate QTc before initiating Quetiapine, and repeat if dose increased or other QT-prolonging agents are added. Quetiapine is a versatile atypical antipsychotic that modulates dopaminergic, serotonergic, and histaminergic pathways — balancing efficacy in mood and psychotic disorders with relatively lower extrapyramidal risk.

🧠 About

• Quetiapine is a second-generation (atypical) antipsychotic with both antipsychotic and mood-stabilising properties.
• It acts as an antagonist at D₂ (dopamine) and 5-HT₂A (serotonin) receptors, with additional effects on histamine (H₁) and α₁-adrenergic receptors.
• It is commonly used in schizophrenia, bipolar disorder, and as adjunctive therapy in major depressive disorder (MDD).
• Notably, Quetiapine has sedative properties, making it useful for agitation or insomnia — but also increasing the risk of orthostatic hypotension.

⚙️ Mechanism of Action

• Antagonist at D₂ and 5-HT₂A receptors → reduces positive symptoms (hallucinations, delusions) and improves negative symptoms (anhedonia, withdrawal).
• Partial agonism at 5-HT₁A may confer antidepressant and anxiolytic benefits.
• Antihistaminic (H₁) and α₁-adrenergic blockade → sedation and postural hypotension.
• Minimal extrapyramidal symptoms (EPS) and prolactin elevation compared to typical antipsychotics.

🎯 Indications

• Schizophrenia.
• Acute mania or mixed episodes (monotherapy or adjunctive with mood stabilisers).
• Depression in bipolar disorder.
• Adjunct in major depressive disorder (low-dose use).
• Psychosis associated with Parkinson’s disease (use cautiously due to hypotension and sedation).

💊 Doses (Oral, Immediate Release)

🔗 Interactions

• Other QT-prolonging drugs — Amiodarone, Sotalol, Methadone, Moxifloxacin, Phenothiazines (chlorpromazine, thioridazine).
• CYP3A4 inhibitors (e.g. erythromycin, ketoconazole, itraconazole) ↑ plasma levels — reduce Quetiapine dose.
• CYP3A4 inducers (e.g. carbamazepine, phenytoin) ↓ plasma levels — may reduce efficacy.
• Concurrent CNS depressants (e.g. alcohol, opioids, benzodiazepines) → enhanced sedation and respiratory depression.

⚠️ Cautions

• Baseline and periodic ECG and QTc (especially with electrolyte disturbance or cardiac disease).
• Monitor for metabolic syndrome — weight, fasting glucose, HbA1c, lipids.
• Gradual titration to reduce risk of hypotension and somnolence.
• In Parkinson’s disease: may worsen motor symptoms at higher doses.
• In elderly or dementia: ↑ mortality and stroke risk — use lowest possible dose, with close review.

🚫 Contraindications

• Prolonged QT interval or family history of congenital long QT syndrome.
• Uncorrected hypokalaemia or hypomagnesaemia.
• Severe hepatic impairment (use with caution and lower doses).

💥 Adverse Effects

• Common: Somnolence, dizziness, dry mouth, constipation, weight gain, orthostatic hypotension.
• Metabolic: Hyperglycaemia, dyslipidaemia, raised triglycerides, insulin resistance.
• Neuropsychiatric: Sedation, restlessness (akathisia), irritability, suicidal ideation (particularly early treatment).
• Endocrine: Mild hyperprolactinaemia, hypothyroidism, SIADH (rare).
• Rare: Pancreatitis, hepatitis, rhabdomyolysis, neuroleptic malignant syndrome (NMS), severe skin reactions (SJS/TEN).

🧩 Monitoring Summary

💡 Teaching Tip

• Quetiapine’s sedation comes from its antihistamine effect — helpful in agitation, but problematic in daytime function.
• Always check ECG and electrolytes before use — especially in polypharmacy, the elderly, or cardiac patients.
• Mnemonic: “Q is for Quiet” — Quetiapine calms psychosis but can make patients too sedated if titrated too fast.
• Emphasise monitoring metabolic effects — atypical antipsychotics are as much endocrine drugs as they are psychiatric ones.

📚 References

• BNF: Quetiapine
• MHRA Drug Safety Update (2019): Antipsychotics and QT prolongation
• NICE NG222 (2023): Psychosis and schizophrenia in adults
• Citrome L. Quetiapine: pharmacology, efficacy and tolerability. CNS Drugs 2020;34(2):93–108.