| Indication |
For the treatment of schizophrenia in adults and in adolescents,
ages 13 to 17, and for the short-term treatment of manic or mixed
episodes of bipolar I disorder in children and adolescents ages 10 to
17. May also be used to manage symptoms of inappropriate behavior due to
aggression and/or psychosis in patients with severe dementia. |
| Pharmacodynamics |
Risperidone is an atypical antipsychotic medication. It is most
often used to treat delusional psychosis (including schizophrenia), but
risperidone is also used to treat some forms of bipolar disorder and
psychotic depression. It also has shown some success in treating
symptoms of Asperger's Syndrome and autism. Risperidone is now the most
commonly prescribed antipsychotic medication in the United States. |
| Mechanism of action |
Blockade of dopaminergic D2 receptors in the limbic system
alleviates positive symptoms of schizophrenia such as hallucinations,
delusions, and erratic behavior and speech. Blockade of serotonergic
5-HT2 receptors in the mesocortical tract, causes an excess
of dopamine and an increase in dopamine transmission, resulting in an
increase in dopamine transmission and an elimination of core negative
symptoms. Dopamine receptors in the nigrostriatal pathway are not
affected by risperidone and extrapyramidal effects are avoided. Like
other 5-HT2 antagonists, risperidone also binds at
alpha(1)-adrenergic receptors and, to a lesser extent, at histamine H1
and alpha(2)-adrenergic receptors. |
| Absorption |
Well absorbed. The absolute oral bioavailability of risperidone is
70% (CV=25%). The relative oral bioavailability of risperidone from a
tablet is 94% (CV=10%) when compared to a solution. |
| Volume of distribution |
|
| Protein binding |
Risperidone, ~88% bound; 9-hydroxyrisperidone, ~77% bound. |
| Metabolism |
Extensively metabolized by hepatic cytochrome P450 2D6 isozyme
to 9-hydroxyrisperidone, which has approximately the same receptor
binding affinity as risperidone. Hydroxylation is dependent on
debrisoquine 4-hydroxylase and metabolism is sensitive to genetic
polymorphisms in debrisoquine 4-hydroxylase. Risperidone also undergoes
N-dealkylation to a lesser extent. |
| Route of elimination |
Risperidone is extensively metabolized in the liver.In healthy
elderly subjects, renal clearance of both risperidone and
9-hydroxyrisperidone was decreased, and elimination half-lives were
prolonged compared to young healthy subjects. |
| Half life |
20-24 hours |
| Clearance |
Not Available |
| Toxicity |
Symptoms of overdose include drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. LD50=82.1mg/kg (orally in mice). |
