Action

Unknown. Antipsychotic effects may occur through antagonism of dopamine D₂ and serotonin 5-HT₂ receptors. Other effects may result partly from antagonism of other receptors, such as histamine H₁ and alpha₁-adrenergic receptors.

Availability

Tablets: 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg

Tablets (extended-release): 50 mg, 150 mg, 200 mg, 300 mg, 400 mg

Indications and dosages

➣ Schizophrenia

Adults: Initially, 25 mg P.O. b.i.d., on day 1, increased by 25 to 50 mg given two to three times daily on days 2 and 3 to range of 300 to 400 mg by day 4. Further adjustments can be made in increments of 25 to 50 mg b.i.d. in intervals of not less than 2 days. Recommended dosage range is 150 to 750 mg/day. Or, 300 mg P.O. (extended-release tablet) once daily, preferably in evening; dosage should be titrated to 400 to 800 mg based on response and tolerability. Dosage increases may be done at 1-day intervals at increments of up to 300 mg.

Children and adolescents ages 13 to 17: Immediate-release tablets administered twice daily, with total daily dosage for initial 5 days of therapy as 50 mg P.O. on day 1, 100 mg on day 2, 200 mg on day 3, 300 mg on day 4, and 400 mg on day 5. After day 5, adjust dosage within recommended range of 400 to 800 mg/day based on response and tolerability. Make dosage adjustments in increments of no greater than 100 mg/day. Based on response and tolerability, may administer three times daily.

➣ Acute manic episodes associated with bipolar I disorder

Adults: Immediate-release tablets administered twice daily, with total daily dosages as 100 mg P.O. on day 1, 200 mg on day 2, 300 mg on day 3, and 400 mg on day 4. Increase in increments of no more than 200 mg/day up to 800 mg/day by day 6. Recommended dosage range is 400 to 800 mg/day. May be given as monotherapy or as adjunctive therapy with lithium or divalproex. Or, extended-release tablets 300 mg P.O. on day 1,600 mg on day 2, and 400 to 800 mg on day 3. Recommended dosage range is 400 to 800 mg/day.

Children and adolescents ages 10 to 17: Immediate-release tablets administered twice daily, with total daily dosage for initial 5 days of therapy as 50 mg P.O. on day 1,100 mg on day 2, 200 mg on day 3,300 mg on day 4, and 400 mg on day 5. After day 5, adjust dosage within recommended range of 400 to 600 mg/day based on response and tolerability. Adjust dosage in increments of no more than 100 mg/day. Based on response and tolerability, may administer three times daily.

➣ Depression associated with bipolar disorder

Adults: Immediate-release or extended-release tablets administered once daily at bedtime as 50 mg P.O. on day 1, 100 mg on day 2, 200 mg on day 3, and 300 mg on day 4. Maximum dosage is 300 mg/day.

➣ Adjunctive treatment of major depressive disorder

Adults: Initially, 50 mg (extended-release) P.O once daily in the evening on days 1 and 2 and 150 mg (extended-release) P.O. once daily on days 3 and 4 as adjunct to existing antidepressive therapy. Recommended dosage is 150 to 300 mg/day.

Dosage adjustment

• Hepatic impairment

• History of hypotensive reactions

• Elderly or debilitated patients

Off-label uses

• Bipolar disorder

• Mania

• Obsessive-compulsive disorder

• Posttraumatic stress disorder

• Psychosis related to Parkinson's disease

Contraindications

• None

Precautions

Use cautiously in:

• diabetes mellitus, hepatic impairment, cardiovascular disease (including family history of QT-interval prolongation, congestive heart failure, and cardiac hypertrophy), cerebrovascular disease, dehydration, hypovolemia, Alzheimer's dementia, hypothyroidism

• history of seizures, suicide attempt, or hypotensive reactions

• history of cardiac arrhythmias such as bradycardia, hypokalemia or hypomagnesemia, concurrent use of other drugs that prolong the QTc interval, congenital QT-interval prolongation (avoid use)

• concurrent use of drugs known to cause electrolyte imbalance

• elderly or debilitated patients

• pregnant patients

• children (safety not established).

Administration

• Monitor fasting blood lipids before treatment.

• Give immediate-release tablets with or without food; give extended-release tablets without food or with a light meal.

Don't confuse Seroquel with Serzone (an antidepressant).

Adverse reactions

CNS: dizziness, sedation, cognitive impairment, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, seizures, suicide

CV: tachycardia, palpitations, peripheral edema, ­orthostatic hypotension, hypertension, QT-interval prolongation

EENT: cataracts, ear pain, rhinitis, pharyngitis

GI: constipation, dyspepsia, dry mouth, anorexia

Hematologic: leukopenia

Metabolic: hypothyroidism

Respiratory: cough, dyspnea

Skin: diaphoresis

Other: weight gain, flulike symptoms, acute withdrawal symptoms with abrupt cessation

Interactions

Drug-drug. Antihistamines, opioids, sedative-hypnotics, other CNS depressants: additive CNS depression

Antibiotics (such as gatifloxacin, moxifloxacin), antipsychotics (such as chlorpromazine, thioridazine, ziprasidone), Class 1A antiarrhythmics (such as procainamide, quinidine), Class III antiarrhythmics (such as amiodarone, sotalol), drugs known to prolong QTc interval (such as levomethadyl acetate, methadone, pentamidine): increased risk of prolonged QTc interval

Antihypertensives: increased risk of hypotension

Barbiturates, carbamazepine, corticosteroids, phenytoin, rifampin, thioridazine: increased clearance and decreased efficacy of quetiapine

Dopamine agonists, levodopa: antagonism of these drugs' effects

Erythromycin, fluconazole, itraconazole, ketoconazole, other CYP450-3A4 inhibitors: increased quetiapine effects

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase: asymptomatic elevations

Total cholesterol, triglycerides: increased levels

Urine tricyclic antidepressant assay: false-positive screen

White blood cells: decreased count

Drug-behaviors. Alcohol use: increased CNS effects

Patient monitoring

Monitor neurologic status, especially for signs and symptoms of tardive dyskinesia, suicidal ideation, or neuroleptic malignant syndrome.

• Be aware that patient should undergo lens examination when starting treatment and at 6-month intervals during long-term treatment.

• Monitor blood pressure for orthostatic hypotension.

Monitor patient closely for prolonged QT interval.

• Monitor fasting blood lipids periodically during treatment.

Monitor CBC and differential in patients with preexisting low white blood cell (WBC) count; discontinue drug at first sign of WBC decrease in absence of other causes.

Patient teaching

• Tell patient to take immediate-release tablets with or without food and to take extended-release form preferably in the evening, swallowed whole, without food or with a light meal.

• Instruct patient not to crush, break, or chew extended-release tablets.

Teach patient to recognize and immediately report signs and symptoms of neuroleptic malignant syndrome (such as high fever, sweating, unstable blood pressure, stupor, muscle rigidity, changes in mood or behavior and tardive dyskinesia) and prolonged QT interval.

• Instruct patient to move slowly when sitting up or standing, to avoid dizziness from sudden blood pressure decrease.

Tell patient not to stop taking drug abruptly. Tell him dosage must be tapered.

• Caution patient not to drink alcohol.

• Instruct patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.