Introduction
Initially approved by the FDA in 1997, quetiapine is a second-generation atypical antipsychotic used in schizophrenia, major depression, and bipolar disorder. Quetiapine demonstrates a high level of therapeutic efficacy and low risk of adverse effects during long-term treatment. It is well-tolerated and a suitable option for some patients with high sensitivity to other drugs, such as Clozapine and Olanzapine.
Uses
Quetiapine is a psychotropic agent used for the management of bipolar disorder, schizophrenia, and major depressive disorder.
Quetiapine is used in the symptomatic treatment of schizophrenia. In addition, it may be used for the management of acute manic or mixed episodes in patients with bipolar I disorder, as a monotherapy or combined with other drugs. It may be used to manage depressive episodes in bipolar disorder. In addition to the above indications, quetiapine is used in combination with antidepressant drugs for the treatment of major depression.
Some off-label uses for this drug include the management of post-traumatic stress disorder (PTSD), generalized anxiety disorder, and psychosis associated with Parkinson's disease.
Associated Conditions
Pharmacodynamics
Quetiapine improves the positive and negative symptoms of schizophrenia and major depression by acting on various neurotransmitter receptors, such as the serotonin and dopamine receptors. In bipolar disorder, it improves both depressive and manic symptoms.
A note on suicidality in young patients and administration in the elderly
Quetiapine can cause suicidal thinking or behavior in children and adolescents and should not be given to children under 10 years of age. It is important to monitor for suicidality if this drug is given to younger patients. In addition, this drug is not indicated for the treatment of psychosis related to dementia due to an increased death rate in elderly patients taking this drug.
Mechanism of Action
Although the mechanism of action of quetiapine is not fully understood, several proposed mechanisms exist. In schizophrenia, its actions could occur from the antagonism of dopamine type 2 (D2) and serotonin 2A (5HT2A) receptors. In bipolar depression and major depression, quetiapine's actions may be attributed to the binding of this drug or its metabolite to the norepinephrine transporter. Additional effects of quetiapine, including somnolence, orthostatic hypotension, and anticholinergic effects, may result from the antagonism of H1 receptors, adrenergic α1 receptors, and muscarinic M1 receptors, respectively.
Absorption
Quetiapine is rapidly and well absorbed after administration of an oral dose. Steady-state is achieved within 48 hours Peak plasma concentrations are achieved within 1.5 hours. The bioavailability of a tablet is 100%. The steady-state Cmax of quetiapine in Han Chinese patients with schizophrenia after a 300 mg oral dose of the extended released formulation was approximately 467 ng/mL and the AUC at steady-state was 5094 ng·h/mL. Absorption of quetiapine is affected by food, with Cmax increased by 25% and AUC increased by 15%.
Volume of Distribution
Quetiapine distributes throughout body tissues. The apparent volume of distribution of this drug is about 10±4 L/kg.
Protein Binding
The protein binding of quetiapine is 83%.
Route of Elimination
After an oral dose of radiolabeled quetiapine, less than 1% of unchanged drug was detected in the urine, suggesting that quetiapine is heavily metabolized. About 73% of a dose was detected in the urine, and about 20% in the feces.
Half Life
The average terminal half-life of quetiapine is about 6-7 hours.
Clearance
The clearance of quetiapine healthy volunteers in the fasted state during a clinical study was 101.04±39.11 L/h. Elderly patients may require lower doses of quetiapine, as clearance in these patients may be reduced by up to 50%. Those with liver dysfunction may also require lower doses.
Toxicity
The oral LD50 if quetiapine in rats is 2000 mg/kg.
Overdose information
Some signs and symptoms of a quetiapine overdose include sedation, drowsiness, tachycardia, and hypotension. Clinical trials demonstrate that overdoses of up to 30 grams of quetiapine did not result in death. A lethal outcome was reported in a clinical trial after an overdose of 13.6 grams of quetiapine. In the case of an acute overdose, ensure to maintain an airway and provide adequate ventilation and oxygenation. Gastric lavage following intubation (if necessary) along with activated charcoal and a laxative may be considered. The possibility of obtundation, seizure or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiac monitoring should also take place.
A note on QT-interval prolongation in an overdose
Postmarketing reports reveal increases in the cardiac QT interval in cases of quetiapine overdose, concomitant illness, and in those taking drugs that increase QT interval or affect electrolyte levels. Note that disopyramide, procainamide, and quinidine may exert additive QT-prolonging effects when administered in patients who have overdosed with quetiapine, and should be avoided.
Food Interactions
- Avoid alcohol.
- Take with or without food. If taken with food, take with a light meal.
Dosage
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.
