Risperidone

Risperidone (pronounced ) is a second generation or atypical antipsychotic, sold under the trade name (Risperdal). It is used to treat schizophrenia (including adolescent schizophrenia), schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism. It is associated with significant weight gain and metabolic problems, as well as tardive dyskinesia and neuroleptic malignant syndrome. Risperidone and other antipsychotics also increase the risk of death in patients with dementia. The drug was developed by Janssen-Cilag and first released in 1994.

Medical uses
Risperidone is used for the treatment of schizophrenia, bipolar disorder, and behavior problems in people with autism. In autism, however, it does not improve conversational ability or social skills, and does not appear to reduce obsessive behavior in most autistic people.

Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993 for the treatment of schizophrenia. 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 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 people with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic people with mild aggression and explosive behavior without an enduring pattern. 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 and chronic use.

Availability


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, as an oral solution, and as an ampule Risperdal Consta, which is a depot injection administered once every two weeks. It is also available as a wafer known in the United States and Canada as Risperdal M-Tabs and elsewhere as Risperdal Quicklets.

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."

Adverse effects
Risperidone has been associated with weight gain. Other common side effects include akathisia, sedation, dysphoria, insomnia, sexual dysfunction, low blood pressure, high blood pressure, muscle stiffness, muscle pain, tremors, hypersalivation, constipation, and stuffy nose. In addition, risperidone treatment can cause photosensitivity and patients should be warned to avoid prolonged exposure to the sun or to use effective sunscreen (SPF 15+). Other skin conditions have also been reported, including rash, xerosis (dry skin), acne vulgaris, alopecia (hair loss), and seborrhea. At high doses skin hyperpigmentation may also occur.

Many antipsychotics are known to cause hyperprolactinemia which may lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia (male breast development), irregular menstruation and sexual dysfunction.

Neuroleptic malignant syndrome has been reported with risperidone, and at least 2 fatal cases of neuroleptic malignant syndrome induced by risperidone have been reported. Tardive Dyskinesia, a irreversible movement disorder, has also been reported with risperidone.

Patients With Dementia
Clinical tests conducted in Canada and the United Kingdom have indicated that  the use of anti-psychotic medications such as risperidone in people with dementia, such as those suffering from Alzheimer's disease, have been linked to higher incidences of death. In addition to a higher rate of death, patients with dementia taking anti-psychotics are susceptible to serious side effects, including stroke.

Pharmacology
Risperidone has been classified as a "qualitatively atypical" antipsychotic agent with a relatively low incidence of extrapyramidal side effects (EPS) (when given at low doses) that has more pronounced serotonin antagonism than dopamine antagonism. Risperidone is unique among most other atypicals in that it has high affinity for the D2 receptor (also known as 'tight binding') whereas most other atypicals have 'loose binding' of the D2 receptor. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, 5-HT2A, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with the typical neuroleptics.


 * 5-HT1A serotonin receptors (Ki = 420nM)
 * 5-HT1D serotonin receptors (Ki = 100nM)
 * 5-HT2A serotonin receptors (Ki = 0.16nM)
 * 5-HT2C receptors (Ki = 26nM)
 * 5-HT7 irreversible antagonist
 * D1 dopaminergic receptors (Ki = 536 nM)
 * D2 dopaminergic receptors (Ki = 3.13 nM)
 * α1 adrenergic receptors (Ki = 0.8 nM)
 * α2 adrenergic receptors (Ki = 7.54 nM)
 * H1 histamine receptors (Ki = 2.23 nM)

It reaches peak plasma levels quickly regardless of whether it is administered as a liquid or pill. Risperidone is metabolized 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. Doses range from 12.5 to 50 mg given as an intramuscular injection once every two weeks.

Brand names
It is sold under the trade name Risperdal in the Netherlands, United States, Canada, Australia, United Kingdom, Portugal, Spain, Turkey, New Zealand, Saudi Arabia, Venezuela, Ireland and several other countries, Risperdal or Ridal in New Zealand and Venezuela, Sizodon or Riscalin in India, Rispolept in Eastern Europe, and Russia,Zepidone in Nigeria, Riperidone in South Korea, Risperidona in Spain and Belivon, or Rispen elsewhere.