Seroquel

Quetiapine

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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	CID 5002
IUPHAR ligand ID	50
DrugBank	DB01224
ChemSpider	4827
Chemical data
Formula	C21H25N3O2S
Mol. mass	383.5099 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	9%
Metabolism	Hepatic
Half-life	6 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C(US)
Legal status	℞-only (US)
Routes	Oral
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Quetiapine (pronounced /kwɨˈtaɪ.əpiːn/ kwi-TYE-ə-peen), marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, both as a quetiapine fumarate salt of the drug, is an atypical antipsychoticschizophrenia, bipolar I mania, bipolar II depression, bipolar I depression, and used off-label for a variety of other purposes, including insomnia and anxiety disorders. used in the treatment of

Annual sales are approximately $4.7 billion worldwide, and $2.9 billion in the U.S.^[1] The patent in the U.S., which was set to expire in 2011, received a pediatric exclusivity extension, which pushed its expiration to March 26, 2012.^[2] The patent already expired in Canada. Several pharmaceutical companies are now making generic versions of quetiapine. Quepin is a generic version manufactured and marketed by Specifar ABEE, Athens, Greece.^[3]

Controversy arose over AstraZeneca's aggressive marketing of the Seroquel for off-label uses, including treatment of PTSD in veterans. Several American soldiers and veterans have died while taking Seroquel.^[4]

Contents [show] 1 Uses 1.1 Investigations 2 Pharmacology 3 Forms 3.1 Dosage 3.2 Sustained-release quetiapine 4 Side effects 4.1 Withdrawal effects 5 Overdosage 6 Recreational use 7 Federal investigations 8 Chemistry 9 References 10 Further reading 11 External links

[edit] Uses

Quetiapine (Seroquel) 25 mg tablets, next to US one-cent coin for comparison.

Quetiapine is indicated for the treatment of schizophrenia, depressive episodes associated with bipolar disorder, acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium or valproate), and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex). Quetiapine received its initial indication from the U.S. Food and Drug Administration for treatment of schizophrenia in 1997.^[5] In 2004, it received its second indication for the treatment of mania-associated bipolar disorder.^[6] It is sometimes used off-label, often as an augmentation agent, to treat conditions such as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression,^[7] Tourette syndrome,^[8] and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.^[9]

In 2005, the National Institute of Mental Health examined quetiapine and other antipsychotics to uncover the comparative efficacy of "second generation" anti-psychotics against older anti-psychotics (known as "first generation" or "typical anti-psychotics"). Such information could be important to the patients, as the newer drugs are far more expensive than their older counterparts. Published in the New England Journal of Medicine, the results of the CATIE ("clinical antipsychotic trials of interventional effectiveness") trial were somewhat mixed. 74% of trial participants (of the 1,493 people who were in different treatment groups) discontinued before the trial ended. The majority of the participants discontinued treatment due to intolerable side effects or lack of efficacy. Olanzapine (Zyprexa) was considered the most effective in terms of the time it took patients to drop out of the study, although it was associated with greater weight gain and glucoseperphenazine.^[10] The CATIE trial was supported by a grant (N01 MH90001) from the NIMH and by the Foundation of Hope of Raleigh, N.C. The individual pharmaceutical companies, whose drugs were used, donated all of the study medication. intolerability found in diabetes patients. The effects of all other treatments (such as Seroquel) were considered to be similar to the effects of the generic (and dramatically less expensive) drug,

A report in British Medical Journal in 2005 showed that quetiapine was ineffective in reducing agitation among Alzheimer's patients, whose usage of the drug constituted 29% of sales. In fact, quetiapine was found to worsen cognitive functioning in elderly patients with dementia.^[11]

Use of quetiapine to minimize the symptoms of opioid withdrawal has been studied.^[12]

[edit] Investigations

In 2007 and 2008, studies were conducted on quetiapine’s efficacy in treating generalized anxiety disorder and major depression. In April 2009, the Psychopharmacologic Drugs Advisory Committee of the US Food and Drug Administration (FDA) held a public meeting to discuss whether study results supported the FDA's approval for anxiety and depression, with risks of metabolic side effects and of tardive dyskinesia and sudden cardiac death.^[13]

In 2010 AstraZeneca was ordered to pay $520 million in a settlement with State and Federal authorities. According to the settlement AstraZeneca promoted the sale and use of Seroquel for uses not approved by the FDA, and paid illegal kickbacks to doctors. As a result of their promotional activity, physicians prescribed Seroquel for children, adolescents and dementia patients in long term care facilities.^[14]

[edit] Pharmacology

Quetiapine has the following pharmacological actions:^{[15][16][17][18]}

• D₁ (IC₅₀ = 1268nM), D₂ (IC₅₀ = 329nM), D₃, and D₄ receptor antagonist
• 5-HT_1A (IC₅₀ = 717nM), 5-HT_2A, 5-HT_2C, and 5-HT₇ receptor antagonist
• α₁-adrenergic (IC₅₀ = 94nM) and α₂-adrenergic receptor (IC₅₀ = 271nM) antagonist
• H₁ receptor (IC₅₀ = 30nM) antagonist
• mACh receptor (IC₅₀ = >5000nM) antagonist (There are contradictions on whether or not this blocks acetylcholine receptors.)

This means Quetiapine is dopamine, serotonin and adrenergic antagonist, anticholinergic substance and antihistamine. Quetiapine binds strongly to serotonin receptors. Serial PET scans evaluating the D₂ receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D₂^[19] Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side effects such as pseudo-parkinsonism as well as elevations in prolactin.^{[citation needed]} receptor.

Zyprexa (? + rex(king))

Olanzapine

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Olanzapine

Systematic (IUPAC) name
2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
Identifiers
CAS number	132539-06-1
ATC code	N05AH03
PubChem	CID 4585
IUPHAR ligand ID	47
DrugBank	DB00334
ChemSpider	10442212
Chemical data
Formula	C17H20N4S
Mol. mass	312.439
SMILES	eMolecules & PubChem
Physical data
Melt. point	195 °C (383 °F)
Solubility in water	Practically insoluble in water mg/mL (20 °C)
Pharmacokinetic data
Bioavailability	87% [1]
Metabolism	Hepatic (direct glucuronidation and CYP mediated oxidation)
Half-life	21–54 hours
Excretion	urine 57%, feces 30%
Therapeutic considerations
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	oral, intramuscular
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Zyprexa 10 mg tablets (AU)

Olanzapine (trade names Zyprexa, Zalasta, Zolafren, Olzapin, Oferta, Zypadhera or in combination with fluoxetine Symbyax) is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder.^[2] Olanzapine is structurally similar to clozapine, but is classified as a thienobenzodiazepine. The olanzapine formulations are manufactured and marketed by the pharmaceutical company Eli Lilly and Company, whose patent for olanzapine proper expires in 2011 (in October 2009 a Canadian judge ruled that the 1991 patent was invalid).^[3] Sales of Zyprexa in 2008 were $2.2B in the US alone, and $4.7B in total.^[4]

Contents [show] 1 Indications and Usage 1.1 Off-label uses 1.1.1 Prevention of psychosis 1.1.2 Use in elderly 2 Dosage and administration 3 Pharmacology 4 Metabolism 5 Side effects, adverse reactions 5.1 Metabolic effects 5.2 Animal Toxicology 6 Overdose 7 Controversy, lawsuits and settlements 8 Chemistry 9 See also 10 Notes and references 11 External links 11.1 Manufacturer site 11.2 Consumer information 11.3 Controversy

[edit] Indications and Usage

• oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with lithium or valproate)
• intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults
• oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults ^[5]

Known FDA approvals are as follows:

• approved for the treatment of the manifestations of psychotic disorders on September 6, 1996^[6]

• approved in combination with fluoxetine for the treatment of depressive episodes associated with Bipolar disorder on December 24, 2003^[7]

• approved for the long-term treatment of bipolar I disorder on January 14, 2004^[8]

• approved in combination with fluoxetine for treatment of resistant depression on March 19, 2009.^[9]

[edit] Off-label uses

Case-reports, open-label, and small pilot studies suggest efficacy of olanzapine for the treatment of some anxiety spectrum disorders (e.g. generalized anxiety disorder,^[10] panic disorder,^[11] post-traumatic stress disorder);^[12] however, olanzapine has not been rigorously evaluated in randomized, placebo-controlled trials for this use and is not FDA approved for these indications. Other common off-label uses of olanzapine include the treatment of eating disorders (e.g. anorexia nervosa) and as an adjunctive treatment for major depressive disorder without psychotic features. It has also been used for Tourette syndrome and stuttering.^[13][14] Olanzapine is also used in many addiction clinics as a sleep aid (usually 2.5–5 mg) due to its low abuse profile and zero addictive properties.

[edit] Prevention of psychosis

Olanzapine has been considered as part of an early psychosis approach for schizophrenia. The Prevention through Risk Identification, Management, and Education (PRIME) study, funded by the National Institute of Mental Health and Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for schizophrenia. The study examined 60 patients with prodromal schizophrenia, who were at an estimated risk of 36–54% of developing schizophrenia within a year, and treated half with olanzapine and half with placebo.^[15] In this study, patients receiving olanzapine had a lower risk of progressing to psychosis, although the difference did not reach statistical significance. Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain.^[16]

[edit] Use in elderly

Citing an increased risk of stroke, in 2004 the Committee on the Safety of Medicines (CSM) in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia. In the U.S., olanzapine comes with a black box warning for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis.^[17][18]

However, a BBC investigation in June 2008 found that this advice was being widely ignored by British doctors.

Risperdal (psedoscience and the psychiatric equivalent to AIDS/HIV/H4)

Risperidone

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Risperidone

Systematic (IUPAC) name
4-[2-[4-(6-fluorobenzo[d]isoxazol-3-yl)- 1-piperidyl]ethyl]-3-methyl- 2,6-diazabicyclo[4.4.0]deca-1,3-dien-5-one
Identifiers
CAS number	106266-06-2
ATC code	N05AX08
PubChem	CID 5073
IUPHAR ligand ID	96
DrugBank	DB00734
ChemSpider	4895
Chemical data
Formula	C23H27FN4O2
Mol. mass	410.485 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	70% (oral)
Metabolism	Hepatic (CYP2D6-mediated)
Half-life	3–20 hours
Excretion	Urinary
Therapeutic considerations
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	Oral and extended-release intramuscular injection
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Risperidone (pronounced Ris-PEAR-rǐ-dōne) is an atypical antipsychotic used to treat schizophreniaschizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in children with autism. The drug was developed by Janssen-Cilag and first released in 1994^[1]. It is sold under the trade name Risperdal in the Netherlands, United States, Canada, Australia, United Kingdom, Portugal, Spain, Turkey, New Zealand and several other countries, Risperdal or Ridal in New Zealand, Sizodon or Riscalin in India, Rispolept in Eastern Europe, and Russia, and Belivon, or Rispen elsewhere. (including adolescent schizophrenia),

Contents [show] 1 Indications and Uses 2 Availability 3 Side effects 4 Pharmacology 5 References 6 External links

[edit] Indications and Uses

• treatment of schizophrenia in adults
• treatment of schizophrenia in adolescents aged 13-17 years
• alone or in combination with lithium or valproate, for the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder in adults
• alone in the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder in children and adolescents aged 10-17 years
• treatment of irritability associated with autistic disorder in children and young adults
• it has also been used as a control drug for people with tourette syndrome and other tic disorders.
• treatment of major depression with psychotic features
• cure persistent or intractable hiccups^[2]

Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993 for the treatment of schizophrenia.^[3]

On August 22, 2007, risperidone was approved as the only drug agent available for treatment of schizophrenia in youth ages 13–17; it was also approved that same day for treatment of bipolar disorder in youth and children ages 10–17, joining lithium. Risperidone contains the functional groups of benzisoxazolepiperidine as part of its molecular structure. In 2003 the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006 the FDA approved risperidone for the treatment of irritability in children and adolescents with autism.^[4] The FDA's decision was based in part on a study of autistic children with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic children with mild aggression and explosive behavior without an enduring pattern.^[5] Like other atypical antipsychotics, risperidone has also been used off-label for the treatment of anxiety disorders, such as obsessive-compulsive disorder; severe, treatment-resistant depression with or without psychotic features; tourette syndrome; disruptive behavior disorders in children; and eating disorders, among others. In two small studies risperidone was reported to successfully treat the symptoms of phencyclidine (PCP) psychosis due to acute intoxication^[6] and chronic use.^[7] and

A 2009 Cochrane Library review found no evidence from randomized controlled trials that risperidone is effective for the treatment of attention-deficit hyperactivity disorder (ADHD) in people with intellectual disabilities.^[8] A multi-year UK study by the Alzheimer's Research Trust suggested that this and other neuroleptic anti-psychotic drugs commonly given to Alzheimer's patients with mild behavioural problems often made their condition worse. The study concluded that:

“

For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status and by some measures improved functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this possibility must be weighed against the unwanted effects of therapy.[9]

”

[edit] Availability

Risperdal 4 mg tablets (UK)

Janssen's patent on Risperdal expired on December 29, 2003, opening the market for cheaper generic versions of the drug from other companies, and Janssen's exclusive marketing rights expired on June 29, 2004 (the result of a pediatric extension.)

Risperidone is available as a tablet in 0.25, 0.5, 1, 2, 3 and 4 mg sizes, as an oral solution (30ml, 1 mg/ml), and as a 12.5 mg, 25 mg, 37.5 mg and 50 mg ampoule Risperdal Consta, which is a depot injectionRisperdal M-Tabs and elsewhere as Risperdal Quicklets. administered once every two weeks. It is also available as a wafer known in the United States and Canada as

Risperidone became available as a generic drug in October 2008 from Teva Pharmaceuticals, Dr. Reddy's Laboratories, Inc. and Patriot Pharmaceutics. The Patriot generic is Janssen Pharmaceutical's "authorized generic pharmaceutical."

[edit] Side effects

Risperidone has been associated with weight gain.^[10] Other common side effects include akathisia, sedation, dysphoria, insomnia, sexual dysfunction, low blood pressure, high blood pressure, muscle stiffness, muscletremors, increased salivation, constipation, and stuffy nose. pain,

Many antipsychotics are known to cause hyperprolactinemia which may lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction. However, risperidone is known to increase prolactin to a greater extent than other atypical antipsychotics. Although lactation is possible in both sexes using other antipsychotic drugs, risperidone is the biggest offender.^[11][12][13] It is thought that once risperidone raises prolactin, it may cause prolactinoma, a benign tumor of the pituitary gland. Tumors, in general, are not considered reversible. Medical therapy may help reduce tumor size and restore normal reproduction and pituitary function, however, dopamine agonists^[14] There is a higher association between pituitary neoplasms with use of risperidone and amisulpride than with other antipsychotic agents. are not likely to be prescribed to antipsychotic users, thus, surgery or radiation treatment may be required. This condition may recur if the patient is switched to a different antipsychotic. Risperidone has been known to cause increased thoughts of suicide.

Risperidone can potentially cause tardive dyskinesia (TD),^[15] extrapyramidal symptoms (EPS),^[15] and neuroleptic malignant syndrome (NMS).^[15] Risperidone may also trigger diabetes and more serious conditions of glucose metabolism, including ketoacidosis and hyperosmolar coma, according to an FDA Warning Letter issued to Janssen Pharmaceutica, Inc. on 19-Apr-04.^[16]

[edit] Pharmacology

This drug belongs to a class of antipsychotic drugs known as atypical antipsychotics that have more pronounced serotonin antagonism than dopamine antagonism, but risperidone is unique in this class because it retains dopamine antagonism. It has high affinity for D₂ dopaminergic receptors. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT_2C, linked to weight gain, 5-HT_2A,linked to its antipsychotic action and relief of some of the extrapyramidal side effects (EPS) experienced with the typical neuroleptics.

It reaches peak plasma levels quickly regardless of whether it is administered as a liquid or pill. Risperidone is metabolised fairly quickly, so the potential for nausea subsides usually in two to three hours. However, the active metabolite, 9-hydroxy-risperidone, which has similar pharmacodynamics to risperidone, remains in the body for much longer, and has been developed as an antipsychotic in its own right, called paliperidone.

An intramuscular preparation, marketed as Risperdal Consta, can be given once every two weeks. It is slowly released from the injection site. This method of administration may be used on sanctioned patients who are declining, or consenting patients who may have disorganized thinking and cannot remember to take their daily doses.^[17] Doses range from 12.5 to 50 mg given as an intramuscular injection once every two weeks.

Lexapro (symbolc misrepresentation)[Lexis-vocabulary, pro-(for, skilled]

Lexapro [Lexis(vocabulary) + Pro]

Escitalopram

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Escitalopram

Systematic (IUPAC) name
(S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
Identifiers
CAS number	128196-01-0
ATC code	N06AB10
PubChem	CID 146570
DrugBank	APRD00683
ChemSpider	129277
UNII	4O4S742ANY
Chemical data
Formula	C20H21FN2O
Mol. mass	324.392 g/mol (414.43 as oxalate)
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	80%
Protein binding	~56%
Metabolism	Liver, specifically the enzymes CYP3A4 and CYP2C19
Half-life	27–32 hours
Therapeutic considerations
Pregnancy cat.	C
Legal status	Rx Only (U.S) POM (U.K)
Routes	Oral
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Lexapro tablets

Cipralex brand escitalopram package and tablet sheet

Escitalopram (trade names Lexapro, Cipralex, Seroplex, Lexamil) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment in adults with major depressive disorder, generalized anxiety disorder, social anxiety disorder , or panic disorder. Escitalopram is the S-stereoisomer (enantiomer) of the earlier Lundbeck drug citalopram, hence the name escitalopram. Escitalopram is noted for its high selectivity of serotonin reuptake inhibition and has side effects typical for the SSRI class.

Contents [show] 1 History 2 Use in depression 3 Pharmacology 4 Side effects and drug interactions 5 Discontinuation symptoms 6 Controversy 7 References 8 Cited texts 9 See also 10 External links

[edit] History

Escitalopram was developed in a close cooperation between Lundbeck and Forest Laboratories. Its development was initiated in the summer of 1997, and the resulting new drug application was submitted to the U.S. FDA in March 2001. The short time (3.5 years) it took to develop escitalopram can be attributed to the previous extensive experience of Lundbeck and Forest with citalopram, which has similar pharmacology.^[1]evergreening"^[2] (also called "lifecycle management"^[3])– the long-term strategy pharmaceutical companies use in order to extend the lifetime of a drug, in this case of the citalopram franchise. Escitalopram is an enantiopure compound of the racemic mixture citalopram, used for the same indication, and for that reason it required less investment and less time to develop. Two years after escitalopram's launch, when the patent on citalopram expired, the escitalopram sales successfully made up for the loss. On May 23, 2006, the FDA approved a generic version of escitalopram by Teva.^[4] On July 14 of that year, however, the U.S. District Court of Delaware decided in favor of Lundbeck regarding the patent infringement dispute and ruled the patent on escitalopram valid.^[5] The FDA issued the approval of escitalopram for major depression in August 2002 and for generalized anxiety disorder in December 2003. Escitalopram can be considered an example of "

In 2006 Forest Laboratories was granted an 828 day (2 years and 3 months) extension on its US patent for escitalopram.^[6] This pushed the patent expiry from December 7, 2009 to March 14, 2012.