Risperidone

From Wikipedia, the free encyclopedia

Not to be confused with reserpine.

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	5073
DrugBank	APRD00187
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

Risperdal tablets

Risperidone (pronounced Ris-PEE-rǐ-dōne and sold under the trade name Risperdal in the Netherlands, United States, Canada, the United Kingdom, Portugal, Spain and several other countries, Risperdal or Ridal in New Zealand, Sizodon or Riscalin in India, Rispolept in Eastern Europe, and Belivon, or Rispen elsewhere) is an atypical antipsychotic developed by Janssen-Cilag.

[edit] Uses

Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993^[1] for the treatment of schizophrenia. On August 22, 2007, Risperdal was approved as the only drug agent available for treatment of schizophrenia in youth ages 13–18; it was also approved that same day for treatment of bipolar disorder in youth and children ages 10–18, joining lithium. Risperidone contains the functional groups of benzisoxazole and piperidine 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. The FDA's decision was based in part on a study of autistic children with severe and enduring problems of tantrums, aggression, and self-injury; risperidone is not recommended for autistic children with mild aggression and explosive behavior without an enduring pattern.^[2] 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.^[3] In two small studies risperidone was reported to successfully treat the symptoms of phencyclidine psychosis due to acute intoxication^[4] and chronic use.^[5]

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:

[edit] Patent status

Janssen's patent on Risperdal expired on December 29, 2007, opening the market for cheaper generic versions of the drug from other companies; however, Janssen had exclusive marketing rights until June 29, 2008, as 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, 1mg/ml), and as a 25 mg, 37.5 mg and 50 mg ampoule Risperdal Consta, which is a depot injection administered once every two weeks. It is also available as a wafer known in the United States as Risperdal M-Tabs and elsewhere as Risperdal Quicklets.

[edit] Generic Availability

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

[edit] Side effects

Common side effects include akathisia, anxiety, dysphoria, insomnia, low blood pressure, muscle stiffness, muscle pain, sedation, sexual dysfunction, tremors, increased salivation, and stuffy nose. Risperidone has been associated with minimal to moderate weight gain, with one study finding that 26 to 38 percent of participants on the drug experienced weight gain.^[7][8]

Occasionally breast tenderness and eventually lactation in both genders may occur. Many antipsychotics are known to increase prolactin because they inhibit dopamine. However, risperidone is known to increase prolactin to a greater extent than most other antipsychotics, such as quetiapine. Over 40 pituitary neoplasm cases have been reported worldwide. It is thought that once risperidone raises prolactin, it may cause prolactinoma, a benign tumor of the pituitary gland. Tumors, in general, aren't considered reversible. Medical therapy (dopamine agonists) may help reduce tumor size and restore normal reproduction and pituitary function, but if unsuccessful, surgery or radiation treatment may be required. This condition may recur if the patient is switched to a different antipsychotic. Risperdone has been known to cause increased thoughts of suicide.^[9]

Risperidone can potentially cause tardive dyskinesia (TD),^[10] extrapyramidal symptoms (EPS),^[10] and neuroleptic malignant syndrome (NMS).^[10] Risperidone may also trigger diabetes and more serious conditions of glucose metabolism, including ketoacidosis and hyperosmolar coma.^[11]

[edit] Pharmacology

This drug belongs to a class of anti-psychotic drugs known as atypical neuroleptics. It is a strong dopamine antagonist. 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 experienced with the typical neuroleptics through action at 5-HT_1A. The latter action may lead to an increased release of dopamine from mesocortical neurones in the brain.

It reaches peak plasma levels quickly regardless of whether it is administered as a liquid or pill. Risperidone is metabolised fairly quickly, so this potential for nausea subsides usually in two to three hours. However, the active metabolite, 9-hydroxy-risperidone, which has similar pharmacodynamics to risperidone, lingers 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 incompliant, or consenting patients who may have disorganized thinking and cannot remember to take their daily doses.^[12] Doses range from 25 to 50 mg given as an intramuscular injection once every two weeks.

[edit] References

[edit] External links

• Drugs.com Professional information on risperidone
• Drugs.com Consumer information on risperidone
• Janssen L.P. official web site on Risperdal (risperidone)
• PubChem Substance Summary: Risperidone National Center for Biotechnology Information.