Quetiapine exerts its therapeutic effects through its action on multiple neurotransmitter systems in the brain. Its key mechanisms include:

1. Dopamine Receptor Antagonism:
   • Quetiapine blocks dopamine D2 receptors in the mesolimbic pathway, reducing positive symptoms of schizophrenia such as hallucinations and delusions.
   • It has a lower affinity for D2 receptors compared to first-generation antipsychotics, which contributes to its reduced risk of extrapyramidal side effects (EPS).
2. Serotonin Receptor Antagonism:
   • Quetiapine strongly blocks serotonin 5-HT2A receptors, which is thought to improve negative symptoms (e.g., social withdrawal, apathy) and cognitive symptoms of schizophrenia.
   • This action also contributes to its efficacy in mood stabilization.
3. Other Receptor Interactions:
   • Quetiapine has affinity for adrenergic α1 and α2 receptors, histamine H1 receptors, and muscarinic M1 receptors, which contributes to its side effect profile (e.g., sedation, orthostatic hypotension, anticholinergic effects).
4. Mood Stabilization:
   • By modulating dopamine and serotonin activity, quetiapine helps stabilize mood in bipolar disorder, particularly in manic, mixed, and depressive episodes.

Quetiapine is approved for a variety of clinical conditions, including:

1. Schizophrenia:
   • Treatment of acute and chronic schizophrenia in adults.
2. Bipolar Disorder:
   • Management of acute manic or mixed episodes.
   • Maintenance treatment to prevent recurrence of manic or depressive episodes.
   • Treatment of bipolar depression.
3. Adjunctive Therapy for Major Depressive Disorder (MDD):
   • Used in combination with antidepressants for adults with MDD who have not responded adequately to antidepressant therapy alone.
4. Generalized Anxiety Disorder (GAD):
   • Treatment of generalized anxiety disorder in some regions (off-label in others).
5. Other Uses:
   • Insomnia (off-label use, particularly at low doses).
   • Agitation and aggression in dementia (off-label use, with caution due to increased mortality risk in elderly patients).

The dosage of quetiapine varies depending on the indication, patient age, and clinical response. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Schizophrenia:
   • Adults: Start with 25 mg twice daily, increasing gradually to a target dose of 300–800 mg daily in divided doses.
2. Bipolar Disorder:
   • Acute Mania: Start with 50 mg twice daily, increasing to 400–800 mg daily in divided doses.
   • Bipolar Depression: Start with 50 mg once daily, increasing to 300 mg daily.
   • Maintenance: 300–800 mg daily in divided doses.
3. Adjunctive Therapy for MDD:
   • Adults: Start with 50 mg once daily, increasing to 150–300 mg daily.
4. Generalized Anxiety Disorder (GAD):
   • Adults: Start with 50 mg once daily, increasing to 150–300 mg daily.

Important Considerations:

• Quetiapine is available in immediate-release (IR) and extended-release (XR) formulations.
• Dose adjustments may be necessary for patients with hepatic or renal impairment.
• Regular monitoring of weight, blood glucose, and lipid levels is recommended due to the risk of metabolic side effects.

Quetiapine is associated with a range of side effects, some of which can be serious. Common side effects include:

1. Central Nervous System:
   • Sedation, dizziness, and somnolence.
   • Extrapyramidal symptoms (EPS) are less common than with first-generation antipsychotics but can still occur.
2. Metabolic Effects:
   • Weight gain, hyperglycemia, and dyslipidemia, which increase the risk of metabolic syndrome and type 2 diabetes.
3. Cardiovascular:
   • Orthostatic hypotension and tachycardia.
4. Gastrointestinal:
   • Constipation, dry mouth, and increased appetite.
5. Other:
   • Elevated prolactin levels, leading to gynecomastia, galactorrhea, or menstrual irregularities.

Serious Side Effects:

• Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening condition characterized by fever, muscle rigidity, and autonomic instability.
• Tardive Dyskinesia: A potentially irreversible movement disorder associated with long-term use of antipsychotics.
• Increased Mortality in Elderly Patients with Dementia: Quetiapine is associated with an increased risk of stroke and death in elderly patients with dementia-related psychosis.

Quetiapine requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Metabolic Monitoring:
   • Regular monitoring of weight, blood glucose, and lipid levels is essential to detect and manage metabolic side effects.
2. Pregnancy and Lactation:
   • Quetiapine should be used during pregnancy only if the potential benefits outweigh the risks. It is excreted in breast milk, so breastfeeding is generally not recommended.
3. Elderly Patients:
   • Lower doses are recommended due to increased sensitivity to side effects, particularly sedation and orthostatic hypotension.
4. Cardiovascular Risk:
   • Use with caution in patients with a history of cardiovascular disease or risk factors for QT prolongation.
5. Suicidal Risk:

Monitor for worsening depression or suicidal thoughts, particularly in patients with mood disorders

Quetiapine has a moderate potential for drug interactions due to its metabolism via cytochrome P450 enzymes (primarily CYP3A4). Key interactions include:

1. CYP3A4 Inhibitors:
   • Ketoconazole and erythromycin can increase quetiapine levels, increasing the risk of side effects.
2. CYP3A4 Inducers:
   • Carbamazepine and phenytoin can decrease quetiapine levels, reducing its efficacy.
3. Central Nervous System Depressants:
   • Alcohol, benzodiazepines, and opioids can enhance sedation and respiratory depression.
4. Antihypertensives:
   • Quetiapine may enhance the hypotensive effects of antihypertensive medications.
5. Other Interactions:
   • Levodopa and dopamine agonists: Reduced efficacy due to dopamine receptor antagonism.

Quetiapine is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Seroquel (a well-known brand in the United States and other regions).
• Seroquel XR (extended-release formulation).
• Ketipinor.
• Quetiapine Accord.