Section 3.1.2.2 Quetiapine

General Description

Quetiapine (Seroquel) is an antipsychotic drug belonging to a new chemical class, the dibenzodiazepine derivatives. For pharmacodynamics, quetiapine is an antagonist at the serotonin 2-A, dopamine 2, alpha 1 and 2, and histamine 1 receptors. The antipsychotic actions appear to involve a combination of serotonin and dopamine antagonism.

The antipsychotic efficacy of quetiapine was initially established in short-term (6 week) studies of schizophrenic inpatients. The effectiveness of quetiapine in long-term studies has not been systematically evaluated. Nevertheless, quetiapine appears to be effective in treating positive and negative symptoms in schizophrenic and schizoaffective disorders.

Indications for Medication

Quetiapine is approved for the treatment of schizophrenia and other psychotic disorders. The other psychotic disorders include schizophreniform disorder, schizaffective disorder, delusional disorder, brief psychotic disorder, psychotic disorder NOS, manic episodes, and major depressive episodes with psychotic features.

Studies have shown similar efficacy with the positive symptoms of schizophrenia, and increased efficacy with the negative symptoms of schizophrenia. Quetiapine may be useful in patients who are treatment resistant to traditional dopamine antagonists and/or patients who have a history of adverse reactions to other, more typical antipsychotic medications.

Clinical Guidelines

The therapeutic range for quetiapine is 150-750mg a day. Patients may be started on a dose of 25mg BID and the dose may be increased by 25-50 mg every several days. The initial target dose is 300-400 mg. A daily schedule of BID/TID dosing is recommended for this medication. Preparations include 25 mg, 100 mg, and 200 mg tablets.

The most effective therapeutic range for quetiapine has yet to be established. The maximum dosage of 750mg a day may be reached with treatment- resistant psychotic patients if they have not responded to the lower 300-400 mg range. Safety in doses greater than 750mg a day has not been demonstrated.

Quetiapine is rapidly absorbed with a peak plasma concentration within 90 minutes, and it has a half-life of 6 hours. Quetiapine is eliminated by hepatic metabolism via the cytochrome 450 enzymes. There are no active metabolites from hepatic metabolism. Clearance is reduced by 40% in elderly patients, so dosage reductions are needed in elderly populations.

Adverse Effects

Quetiapine has been associated with cataracts in chronic dog studies. Lens changes have also been observed in patients during long-term quetiapine treatment, but a causal relationship to quetiapine use has not been established. Nevertheless, the possibility of lenticular changes cannot be excluded at this time. Therefore, when the psychiatrist has established that quetiapine has been effective and that it is going to be continued, it is recommended to obtain a "baseline" examination of the lens by methods adequate to detect cataract formation, such as slit lamp exam or other appropriately sensitive methods, and at 6 month intervals during chronic treatment.

Quetiapine is associated with orthostatic hypotension during the initial dose titration due to the alpha ? blockade. Somnolence may occur due to H 1 blockade. Patients who are involved in the operation of hazardous machinery/cars should be cautioned on this side effect until they are certain that quetiapine does not impair their motor or cognitive skills.

Quetiapine is associated with minimal EPS, minimal weight gain, and no anticholinergic side effective. Quetiapine may be associated with tardive dyskinesia and neuroleptic malignant syndrome; but these adverse effects should occur less with quetiapine than with the traditional antipsychotic medications.

Quetiapine is generally well tolerated. Dyspepsia and abdominal pain may occur with this medication. Cholesterol and triglycerides elevations may occur in the 10-17% range. But there is no sustained elevation of prolactin.

Patients should be advised to notify their physicians if they intend to become pregnant during medication therapy. Quetiapine is a Category C drug and should be used with caution in pregnancy. Quetiapine passes into breast milk. Quetiapine should not be used with nursing mothers.

Drug-Drug Interactions

Quetiapine has a low potential for drug-drug interactions. For overdose, quetiapine has a high margin of safety. Patients overdosing on 1200 mg to 9600 mg have survived with no permanent impairments.

Quetiapine may need to be increased if administered with phenytoin. Phenytoin can increase elimination by a 5-fold factor. To maintain control of psychotic symptoms, quetiapine should be increased, possibly toward the 750 mg daily limit. Any dosages above 750 mg should be well documented with clear detailed rationale.

The consent form for this medication is "Major Tranquilizer - Low Potency".