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Seroquel



Quetiapine (kwe-TYE-a-peen), marketed by AstraZeneca with the brand name Seroquel, is one of the atypical antipsychotics. Quetiapine has FDA and international approvals for the treatment of schizophrenia and acute mania in bipolar disorder. It is used "off-label" to treat other disorders, such as post-traumatic stress disorder, obsessive compulsive disorder, anxiety disorders, hallucinations in Parkinson's disease patients using Requip, and as a sedative for those with sleep disorders. It also is effective to treat depressive episodes associated with bipolar depression, in which AstraZeneca is seeking FDA approval for monotherapy treatment for Bipolar depression.


Chemistry


Quetiapine (shown in figure) is 11--1-piperazinyl]dibenzothiazepine, C21H25N3O2S. Dosages are based on milligrams of this base. The Seroquel formulation is as a fumarate salt with the chemical formula C42H50N6O4S2  -C4H4O4 and systematic name 2- thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol fumarate (2:1) (salt).

Seroquel Drug
Pharmacology
The antipsychotic effect of quetiapine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Specifically the D1, D2, 5-HT1A and 5-HT2 receptor subtypes are antagonized. Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor. Theoretically, this allows for normal physiological surges of dopamine to elicit their normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side effects such as pseudo-parkinsonism and elevations in prolactin.

Quetiapine also has an antagonistic effect on the histamine H1 receptor. This may be responsible for the sedative effect of the drug.

Dosage
While the mean effective dose is typically between 300 and 600 mg daily, it is offered in 25, 100, 200 and 300 mg oral doses. Initial dosage may be as low as 25 to 50 mg, prescribed in divided doses throughout the day (typically evening and morning). Initial reaction to Quetiapine may be somnolence. As such, care is taken to avoid over exposure to the drug during the first few doses. After a patient becomes more familiar with the effects, the dosage may be slowly "ramped up." AstraZeneca claims that a healthcare provider can "achieve up to 800mg/day in less than a week." Such large doses are provided throughout a full day in divided, roughly equal doses.

When starting dosages in elderly patients. The usual dosage adjustments come in four steps, and more if needed. Usually starting at 25mg at night. Then going to 50mg at night, 25mg at day and 50 at night, 50mg in the day and then 50mg at night. The dosage may be increased if needed. This dosaging is similar to the dosage required for younger adults.

Side effects
The most common side effect is sedation. Seroquel will put the patient into a drowsy state, and will help the patient fall asleep. Even though official guidelines call for the quetiapine dosage to be divided throughout the day, many prescriptions call for the entire dose to be taken before bedtime because of its sedative effects. Although quetiapine is approved by the FDA for the treatment of schizophrenia and bipolar disorder, it is frequently prescribed for "off-label" purposes including insomnia or the treatment of anxiety disorders. Because of its sedative properties, reports of quetiapine abuse (sometimes by snorting crushed tablets intranasally) have emerged in the medical literature (such abuse is common with other antipsychotics, such as Thorazine).

Other common side effects include: agitation, memory problems, headache, abnormal liver tests, dizziness, upset stomach, and stuffy nose feeling.

Quetiapine is believed to be less likely to cause extrapyramidal side effects and tardive dyskinesia than typical antipsychotics. As with other antipsychotics, extrapyramidal side effects are a problem for some.

Weight gain can be a problem for some patients using quetiapine, by causing the patient's appetite to persist even after meals. However, this effect may occur to a lesser degree compared to some other atypical antipsychotics such as olanzapine or clozapine. Like other atypical antipsychotics, there is some evidence suggesting a link to the development of diabetes, however this remains unclear and controversial.

Studies conducted on beagles have resulted in the formation of cataracts -- while there are reports of cataracts occurring in humans, controlled studies including thousands of patients have not demonstrated a clear casual association between this side effect and quetiapine therapy.

As with some other antipsychotics, Quetiapine may lower the seizure threshold, and should be taken with care in combination with drugs such as Bupropion.

Other useful drug information: Strattera | Luvox | Benicar | Amiodarone | Alprazolam | Evista | Prometrium

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