Quetiapine
Systematic (IUPAC) name
2-(2-(4-dibenzo[b,f][1,4]thiazepine- 11-yl-1-piperazinyl)ethoxy)ethanol
Identifiers
CAS number	111974-69-7
ATC code	N05AH04
PubChem	5002
DrugBank	APRD00675
Chemical data
Formula	C21H25N3O2S
Mol. mass	383.5099 g/mol
Pharmacokinetic data
Bioavailability	100% in 1.5hr
Metabolism	Hepatic
Half life	6 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	Oral

Quetiapine (pronounced kwe-TYE-a-peen or kwəˈtɑɪəˌpiːn), marketed by AstraZeneca, with the brand name Seroquel, belongs to a series of neuroleptics known as "atypical antipsychotics", which have, over the last two decades, become increasingly popular alternatives to "typical antipsychotics", such as haloperidol (Haldol).

Uses

Quetiapine has the United States Food and Drug Administration (FDA) and international approvals for the treatment of schizophrenia, treatment as an adjunct to either Lithium or Divalproex, and acute mania in bipolar disorder. Additionally, in October 2006, Seroquel was approved by the FDA for the treatment of depressive episodes associated with Bipolar I (or Bipolar-II) Disorder.^[1][2] Currently, Seroquel is the only agent approved for this indication—as a single agent monotherapy. It is also used off-label to treat other disorders, such as post-traumatic stress disorder, restless legs syndrome, alcoholism, hallucinations in Parkinson's disease patients using ropinirole, Tourette syndrome,^[3] and as a sedative for those with sleep disorders or anxiety disorders.

Pharmacology

Seroquel logo

The antipsychotic effect of quetiapine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Specifically the dopamine D1 and D2;, 5-HT_1A 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.

Forms

Quetiapine is available under the brand name Seroquel. It was originally available in 25 mg, 100 mg, 200 mg, and 300 mg tablets, however 50 mg, 400 mg, and 500 mg tablets were added to increase dosing flexibility.

Quetiapine Sustained Release (Seroquel SR)

AstraZeneca has submitted New Drug Application for a sustained release version of quetiapine in the United States, Canada, and the European Union in the second half of 2006 for treatment of schizophrenia.^[4][5] AstraZeneca will retain the exclusive right to market sustained release quetiapine until year 2017.

Phase III trials are being conducted to prove quetiapine's efficacy in treating generalized anxiety disorder and major depressive disorder as of January 2007. The company expects to file New Drug Application for treating generalized anxiety disorder in the second half of 2007 and for major depressive disorder in 2008.^[6]

Dosage

Quetiapine is available in 25, 50, 100, 200, 300 and 400mg oral doses, all in tablet and gelcap forms. While the effective dose for schizophrenia is typically between 300 and 600 mg daily, doses as high as 1000 mg daily are sometimes prescribed, depending on the patients' prognosis. In Bipolar-I Disorder, Mania—the FDA approved initial dosage is 100mg, prescribed twice-daily. In Bipolar-I/II Disorder, Depression —the FDA approved initial dosage is 50mg at bedtime. While not FDA approved, dosage for sleep and dementia is typically 25 to 100 mg. Initial reaction to quetiapine may be somnolence. As such, care is taken to avoid over-exposure to the drug during the first few dosage increases, and to take the drug at bedtime where possible. For anxiety disorders the typical dosage is 25mg, one to four times per day. After receptor site binding, physicians may increase dosages (in 100mg increments daily) based on the individual needs for the patient (Target dose in acute mania = 400-800 mg/day, depressive episodes associated with bipolar I/II disorder = 300 mg/day, schizophrenia = 400-800 mg/day). Due to its low affinity for the D² receptor site, the dosage of quetiapine is often different than with other atypical antipsychotics; AstraZeneca claims that a healthcare provider can "achieve up to 600/day in less than a week." Such large doses are provided throughout a full day in divided dosing schedules.

Care is needed when starting dosages in elderly patients. The usual dosage adjustments come in four or more steps. The order usually begins with 25 mg for elderly patients or 100 mg/day in adults.

Side effects

The most common side effect of Seroquel is sedation, and is prescribed specifically (off-label) for this effect in patients with sleep disorders. Seroquel's newest indication, for Bipolar Depression, specifically calls 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. Seroquel is not classified as a controlled substance, however reports of quetiapine abuse (sometimes by insufflating, then crushed tablets) have emerged in medical literature; for the same reason, abuse of other antipsychotics, such as chlorpromazine (Thorazine®), may occur as well, but research related to the abuse of typical antipsychotics is limited.

Common side effects include: constipation, headache, and mild weight gain. Less common side effects (less than 2% of patients) include: abnormal liver tests, dizziness, upset stomach, substantial weight gain, a stuffy nose, and increased paranoia.

Of note is the somnolence/sedation that occurs with Seroquel - as this side effect is most pronounced within the first 7 days of treatment and decreases over time thereafter.

There is a significant risk of development of the incurable neurological disorder tardive dyskinesia with any prolonged use of any neuroleptic drug. However, quetiapine is believed to be less likely to cause tardive dyskinesia^[7][8] somewhat less often than typical antipsychotics based on the data sources which point to placebo-level incidence of extrapyramidal side effects (a claim that only Seroquel can make, based on current research).

The rare, but life-threatening, neuroleptic malignant syndrome may also result from quetiapine use.

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 causal association between quetiapine therapy and this side effect. (Reference needed to April 2006 results of CATIE study.) However, the Seroquel® website[1] still recommends that you have your eyes examined every six months.

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

Notes and references

External links

• Seroquel Patient Reports
• MedlinePlus DrugInfo uspdi-203124
• Compound #1802: Quetiapine ChemBank
• Seroquel on RxList
• BOLDER II study says that Quetiapine more effective than other drugs
• The Down Side of Happy Pills: Living life medicated.
• Intranasal Quetiapine Abuse