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.

Abilify (Phi)(ability)

Double play on words (Phi, Ability), comp. lexapro

 Aripiprazole

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Aripiprazole

Systematic (IUPAC) name
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one
Identifiers
CAS number	129722-12-9
ATC code	N05AX12
PubChem	CID 60795
IUPHAR ligand ID	34
DrugBank	APRD00638
ChemSpider	54790
UNII	82VFR53I78
Chemical data
Formula	C23H27Cl2N3O2
Mol. mass	448.385
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	87%
Protein binding	>99%
Metabolism	liver
Half-life	75h (active metabolite : 94h)
Excretion	feces and urine
Therapeutic considerations
Licence data	EU EMA:Link, US FDA:link
Pregnancy cat.	C (USA)
Legal status	℞ Prescription only
Routes	oral (via tablets, orodispersable tablets, and oral solution); intramuscular
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Aripiprazole (pronounced /ˌɛərɨˈpɪprəzoʊl/ AIR-i-PIP-rə-zohl; brand names: Abilify, Abilify Discmelt, Aripiprex) is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression. It was approved by the US Food and Drug Administration (FDA) for schizophrenia on November 15, 2002, for acute manic and mixed episodes associated with bipolar disorder on October 1, 2004, as an adjunct for major depressive disorder on November 20, 2007 and to treat irritability in children with autistic disorder in children on 20 November 2009.^[1][2] Aripiprazole was developed by Otsuka in Japan, and in the United States, Otsuka America markets it jointly with Bristol-Myers Squibb.

Contents [show] 1 Indications and usage 1.1 Schizophrenia 1.2 Bipolar disorder 1.3 Major depression (Unipolar depression) 1.4 Autism 1.5 Cocaine dependency 2 Pharmacology 3 Pharmacokinetics 4 Patent status 5 Side effects 6 Overdosage 7 Drug interactions 8 Dosage forms 9 Synthesis 10 References 11 External links

[edit] Indications and usage

[edit] Schizophrenia

Aripiprazole has been approved by the FDA for the treatment of schizophrenia.^[3]

[edit] Bipolar disorder

Aripiprazole has been approved by the FDA for the treatment of acute manic and mixed episodes, in both pediatric patients aged 10–17 and in adults.^[4] Several double-blind, placebo-controlled trials support this use.^[5][6][7][8] In addition, it is often used as maintenance therapy, either on its own or in conjunction with a mood stabilizer such as lithium or valproate. This use is also supported by a handful of studies.^[9][10]haloperidol at reducing manic symptoms,^{[11][unreliable source?]} and is much better tolerated by patients.^[12] Aripiprazole is at least as effective as
Aripiprazole's use as a monotherapy in bipolar depression is more controversial. While a few pilot studies have found some effectiveness^[13][14] (with one finding a reduction in anhedonia symptoms^[15]), two large, double-blind, placebo-controlled studies found no difference between aripiprazole and placebo.^[16] One study reported depression as a side effect of the drug.^[17]

[edit] Major depression (Unipolar depression)

In 2007, aripiprazole was approved by the FDA for the treatment of unipolar depression when used adjunctively with an antidepressant medication.^[18] It has not been FDA-approved for use as monotherapy in unipolar depression.

[edit] Autism

In 2009, the United States FDA approved Abilify to treat irritability in persons with autism.^[19] It was approved on the basis of two studies that showed it reduced aggression towards others, self-injury, quickly changing moods, irritability, and temper tantrums in autistic males and females 6–17 years of age.

[edit] Cocaine dependency

Perhaps owing to its mechanism of action relating to dopamine receptors, there is some evidence to suggest that aripiprazole blocks cocaine-seeking behaviour in animal models without significantly affecting other rewarding behaviours (such as food self-administration). ^[20]

[edit] Pharmacology

D2 Partial Agonist (Ki = 0.34 nM) D3 Antagonist (?)

5-HT1A Partial Agonist (Ki = 0.34 nM) 5-HT2A Antagonist (Ki = 0.8 nM) 5-HT2C Partial Agonist (Ki = 15 nM) 5-HT7 Antagonist (Ki = 39 nM)

SRI (?) Antihistamine (Ki = 61 nM) α-adrenergic antagonist (Ki = 57 nM) mACh receptor antagonist (?)

Aripiprazole's mechanism of action is different from those of the other FDA-approved atypical antipsychoticsclozapine, olanzapine, quetiapine, ziprasidone, and risperidone). Rather than antagonizing the D₂ receptor, aripiprazole acts as a D₂ partial agonist (K_i = 0.34 nM).^[21][22] Aripiprazole is also a partial agonist at the 5-HT_1A receptor (K_i = 1.65 nM), and like the other atypical antipsychotics displays an antagonist profile at the 5-HT_2A receptor (K_i = 0.8 nM).^[23][24] It also antagonizes the 5-HT₇ receptor (K_i = 39 nM) and acts as a partial agonist at the 5-HT_2C receptor (K_i = 15 nM), both with high affinity. The latter action may underlie the minimal weight gain seen in the course of therapy.^[25] Aripiprazole has moderate affinity for histamine (K_i = 61 nM) and α-adrenergic (K_i = 57 nM) receptors and for the serotonin transporter, and no appreciable affinity for cholinergic muscarinic receptors.^[26] (e.g.,
D₂ and D₃ receptor occupancy levels are high, with average levels ranging between ~71% at 2 mg/day to ~96% at 40 mg/day.^[27][28] Most atypical antipsychotics bind preferentially to extrastriatal receptors, but aripiprazole appears to be less preferential in this regard, as binding rates are high throughout the brain.^[29]
Recently, it has been demonstrated that in 5-HT₇ receptor knockout mice, aripiprazole does not reduce immobility time in the forced swim test (FST), and actually increases it.^[30][31] This implicates 5-HT₇amisulpride.^[30][31][32] antagonism as playing a major role in aripiprazole's antidepressant effects, similarly to
Aripiprazole produces 2,3-dichlorophenylpiperazine (DCPP) as a metabolite similarly to how trazodone and nefazodone reduce to 3-chlorophenylpiperazine (mCPP) and niaprazine converts to 4-fluorophenylpiperazine^[33] It is unknown whether DCPP contributes to aripiprazole's pharmacology in any way, but the possibility cannot be excluded. (pFPP).

[edit] Pharmacokinetics

Aripiprazole displays linear kinetics and has an elimination half-life of approximately 75 hours. Steady-state plasma concentrations are achieved in about 14 days. C_max (maximum plasma concentration) is achieved 3–5 hours after oral dosing. Bioavailability of the oral tablets is about 90% and the drug undergoes extensive hepatic metabolization (dehydrogenation, hydroxylation, and N-dealkylation), principally by the enzymes CYP2D6 and CYP3A4. Its only known active metabolite is dehydro-aripiprazole, which typically accumulates to approximately 40% of the aripiprazole concentration. The parenteral drug is excreted only in traces, and its metabolites, active or not, are excreted via feces and urine.^[26] When dosed daily, brain concentrations of aripiprazole will increase for a period of 10–14 days, before reaching stable constant levels. This phenomenon is due to the long half life of aripiprazole, and is responsible for many of the adverse side effects that appear after multiple days of dosing (whereas the first dose normally does not cause these side effects).

[edit] Patent status

Otsuka's US patent on aripiprazole expires on October 20, 2014;^[34] however, due to a pediatric extension, a generic will not become available until at least April 20, 2015.^[4] Barr Laboratories (now Teva Pharmaceuticals) initiated a patent challenge under the Hatch-Waxman Act in March 2007.^[35] As of 14 August 2009, this challenge is still in court. (2009 -08-14)^[update]

[edit] Side effects

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Akathisia^[36], headache, unusual tiredness or weakness, nausea, vomiting, an uncomfortable feeling in the stomach, constipation, light-headedness, insomnia, sleepiness, shaking, and blurred vision.
Uncontrollable twitching or jerking movements, tremors, seizure, and weight gain. Some people may feel dizzy, especially when getting up from a lying or sitting position, or may experience a fast heart rate.
Neuroleptic malignant syndrome (Combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness, and sudden change in blood pressure and heart rate.)
Aripiprazole also causes sexual dysfunction.
Tardive dyskinesia (As with all antipsychotic medication, patients using aripiprazole may develop the permanent neurological disorder tardive dyskinesia.^[37][38][39])
Stroke (While taking aripiprazole some elderly patients with dementia have suffered from stroke or 'mini' stroke.)
Other elderly patients may experience high blood sugar or the onset or worsening of diabetes.
Allergic reaction (such as swelling in the mouth or throat, itching, rash), increased production of saliva, speech disorder, nervousness, agitation, fainting, reports of abnormal liver test values, inflammation of the pancreas, muscle pain, weakness, stiffness, or cramps.

[edit] Overdosage

Children or adults who ingested acute overdoses have usually manifested central nervous system depression ranging from mild sedation to coma; serum concentrations of aripiprazole and dehydroaripiprazole in these patients were elevated by up to 3-4 fold over normal therapeutic levels, yet no deaths have yet been recorded.^[40]

[edit] Drug interactions

Aripiprazole is a substrate of CYP2D6 and CYP3A4. Coadministration with medications that inhibit (e.g. paroxetine, fluoxetine) or induce (e.g. carbamazepine) these metabolic enzymes are known to increase and decrease, respectively, plasma levels of aripiprazole.^[41] As such, anyone taking Abilify should be aware that their dosage of Abilify may need to be decreased.
Aripiprazole may change the subjective effects of alcohol. One study^[42] found that aripiprazole increased the sedative effect and reduced the sense of euphoria normally associated with alcohol consumption. However, another alcohol study^[43] found that there was no difference in subjective effect between a placebo group and a group taking aripiprazole.

[edit] Dosage forms

• Intramuscular injection, solution: 7.5 mg/mL (1.3 mL)
• Solution, oral: 1 mg/mL (150 mL) [contains propylene glycol, sucrose 400 mg/mL, and fructose 200 mg/mL; orange cream flavor]
• Tablet: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg
• Tablet, orally disintegrating: 10 mg [contains phenylalanine 1.12 mg; creme de vanilla flavor]; 15 mg [contains phenylalanine 1.68 mg; creme de vanilla flavor]

[edit] Synthesis

U.S. Patent 5,006,528

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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.