Quetiapine
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| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 100% in 1.5hr |
| Metabolism | Hepatic |
| Elimination half-life | 6 hours |
| Excretion | Renal |
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| ECHA InfoCard | 100.131.193 |
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| Formula | C21H25N3O2S |
| Molar mass | 383.5099 g/mol g·mol−1 |
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.[2][3] 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,[4] and as a sedative for those with sleep disorders.
Chemistry
Quetiapine (shown in figure) is 11-[4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1,4]thiazepine, 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-[2-(4-dibenzo [b,f] [1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol fumarate (2:1) (salt).
Pharmacology
The antipsychotic effect of quetiapine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Specifically the D&mdash1;1, 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 D&² 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 and 400 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.[5][6] 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.[7]
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 doses. 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
As quetiapine is a sedative, the most common side effect is sedation, and is prescribed specifically (off-label) for this effect in patients with sleep disorders. It is one of the most sedating of all anti psychotic drugs, rivaling even the most sedating older antipsychotics. 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 rather mild sedative side effects, 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.
Other common side effects include: agitation, constipation, memory problems (anterograde amnesia in particular is very common), headache, abnormal liver tests, dizziness, upset stomach, substantial weight gain, a stuffy nose, and increased paranoia. They have the tendency to weaken with time, being most pronounced during the first week of treatment.
Two rare but serious side effects from quetiapine are neuroleptic malignant syndrome and tardive dyskinesia. However, quetiapine is believed to be less likely to cause tardive dyskinesia[8][9] than typical antipsychotics based on the data sources which point to placebo-level incidence of extrapyramidal side effects. 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
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ astrazeneca.com October 20, 2006, retrieved November 19, 2006.
- ^ Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression: A Double-blind, Placebo-controlled Study (The BOLDER II Study). Journal of Clinical Psychopharmacology, December 2006, retreived November 19, 2006.
- ^ Quetiapine treatment of children and adolescents with Tourette's disorder. Fall 2003, retrieved January 27, 2007.
- ^ AstraZeneca Submits an NDA For Sustained Release Formulation SEROQUEL SR™. For the treatment of [[schizophrenia. July 18, 2006, retrieved January 1, 2007
- ^ AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation SEROQUEL SR™ for the Treatment of Schizophrenia. October 19, 2006, retrieved January 1, 2007
- ^ AstraZeneca—Pipeline Summary—New chemical entities and line extensions. Retrieved January 5, 2007
- ^ "Quetiapine-related tardive dyskinesia".
- ^ "Tardive dyskinesia with quetiapine".