The mechanism of action of Quetiapine, as with other drugs having efficacy in the treatment of schizophrenia and acute manic episodes associated with bipolar disorder, is unknown. However, it has been proposed that this drug's efficacy in schizophrenia is mediated through a combination of dopamine type 2 (D2 ) and serotonin type 2 (5HT2) antagonism. Antagonism at receptors other than dopamine and 5HT 2 with similar receptor affinities may explain some of the other effects of Quetiapine. Quetiapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Quetiapine's antagonism of adrenergic α1 receptors may explain the orthostatic hypotension observed with this drug.

Quetiapine is indicated for the treatment of Acute and chronic psychoses, including schizophrenia, Bipolar Disorder including: treatment of manic episodes satisfying DSM-IV criteria for mania associated with bipolar disorder, treatment of depressive episodes associated with bipolar disorder, maintenance treatment of bipolar I disorder, in combination with a mood stabilizer, for the prevention of recurrence of manic, depressive or mixed episodes.

Acute and chronic psychoses, including schizophrenia: Quetiapine should be administered twice daily, with or without food. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). From Day 4 onwards, the dose should be titrated to the usual effective dose range of 300-450 mg/day. However, this may be adjusted, depending on the clinical response and tolerability of the individual patient, within the range 150 to 750 mg/day.

Manic episodes associated with bipolar disorder: Quetiapine should be administered twice daily, with or without food. The total daily dose for the first four days of therapy is 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3) and 400 mg (Day 4). Further dosage adjustments up to 800mg/day by Day 6 should be in increments of no greater than 200 mg/day. The dose may be adjusted depending on clinical response & tolerability of the individual patient, within the range of 200 to 800 mg/day. The usual effective dose is in the range of 400 to 800mg/day.

Depressive episodes associated with bipolar disorder: Quetiapine should be administered once daily at bedtime, with or without food. The usual dose is 300 mg/day. The daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). Quetiapine can be titrated to 400 mg on Day 5 and up to 600mg by Day 8. Antidepressant efficacy was demonstrated with Quetiapine at 300mg and 600 mg, however no additional benefit was seen in the 600mg group during short term treatment.

Maintenance treatment of bipolar I disorder in combination with mood stabilizers: Patients who have responded to Quetiapine in combination therapy with a mood stabiliser for acute treatment of bipolar disorder should continue on Quetiapine therapy at the same dose. Quetiapine dose can be re-adjusted depending on clinical response and tolerability of the individual patient. Efficacy was demonstrated with Quetiapine (administered twice daily totalling 400mg to 800mg a day) as combination therapy with a mood stabilizer.

Quetiapine is contra-indicated in patients who are hypersensitive to it.

The most commonly reported Adverse Drug Reactions (ADRs) with Quetiapine are somnolence, dizziness, dry mouth, withdrawal (discontinuation) symptoms, elevations in serum triglyceride levels, elevations in total cholesterol (predominantly LDL cholesterol), decreases in HDL cholesterol, weight gain, decreased haemoglobin and extrapyramidal symptoms.

Overdose Effects

In clinical trials, survival has been reported in acute overdoses of up to 30 grams of Quetiapine. There is no specific antidote to Quetiapine. In cases of severe intoxication, the possibility of multiple drug involvement should be considered, and intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system. In cases of Quetiapine overdose, refractory hypotension should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents (adrenaline and dopamine should be avoided, since beta stimulation may worsen hypotension in the setting of Quetiapine-induced alpha blockade). Close medical supervision and monitoring should be continued until the patient recovers.

• Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. 
• Concomitant Illness: Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. Quetiapine may induce orthostatic hypotension especially during the initial dose-titration period. 
• Seizures: As with other antipsychotics, caution is recommended when treating patients with a history of seizures.
• Tardive Dyskinesia and Extrapyramidal Symptoms (EPS): If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of Quetiapine should be considered.
• Neuroleptic Malignant Syndrome: This syndrome has been associated with antipsychotic treatment. Quetiapine should be discontinued and appropriate medical treatment given.
• QT Prolongation: As with other antipsychotics, caution should be exercised when Quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation.
• Neutropenia: Severe neutropenia (<0.5x109/L) has been uncommonly reported in Quetiapine clinical trials. Most cases of severe neutropenia have occurred within the first two months of starting therapy with Quetiapine.
• Hyperglycemia & diabetes mellitus: Increases in blood glucose and hyperglycaemia, and occasional reports of diabetes, have been observed in clinical trials with Quetiapine.

Use in Special Populations

Elderly: As with other antipsychotics, Quetiapine should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration may need to be slower, and the daily therapeutic dose lower, than that used in younger patients, depending on the clinical response and tolerability of the individual patient. The mean plasma clearance of Quetiapine was reduced by 30% to 50% in elderly subjects when compared with younger patients.

Children and Adolescents: Quetiapine is not indicated for use in children and adolescents below 18 years of age.

Pregnancy & Lactation

The safety and efficacy of Quetiapine during human pregnancy have not been established. Therefore, Quetiapine should only be used during pregnancy if the benefits justify the potential risks and the administered dose and duration of treatment should be as low and as short as possible. The degree to which Quetiapine is excreted into human milk is unknown. Women who are breast-feeding should therefore be advised to avoid breast-feeding while taking Quetiapine.