Brands, Medical Use, Clinical Data
Brands / Synonyms
Risperdal; Risperdal Consta; Risperdal M-Tab; Risperidal M-Tab; Risperidona [Spanish]; Risperidone [Usan:Ban:Inn]; Risperidonum [Latin]; Risperin; Rispolept; Rispolin; Sequinan
For the treatment of schizophrenia.
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.
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.
Symptoms of overdose include drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. LD50=82.1mg/kg (orally in mice).
Biotrnasformation / Drug Metabolism
RISPERDAL® (risperidone) is contraindicated in patients with a known hypersensitivity
to the product.
The interactions of RISPERDAL® and other drugs have not been systematically evaluated.
Given the primary CNS effects of risperidone, caution should be used when RISPERDAL® is taken in
combination with other centrally acting drugs and alcohol.
Because of its potential for inducing hypotension, RISPERDAL® may enhance the
hypotensive effects of other therapeutic agents with this potential.
RISPERDAL® may antagonize the effects of levodopa and dopamine agonists.
Amytriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic
fraction. Cimetidine and ranitidine increased the bioavailability of risperidone, but only marginally increased the
plasma concentration of the active antipsychotic fraction.
Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.
Carbamazepine and Other Enzyme Inducers
In a drug interaction study in schizophrenic patients, 11 subjects received risperidone titrated to 6
mg/day for 3 weeks, followed by concurrent administration of carbamazepine for an additional 3 weeks. During
co-administration, the plasma concentrations of risperidone and its pharmacologically active metabolite,
9-hydroxyrisperidone, were decreased by about 50%. Plasma concentrations of carbamazepine did not appear to be
affected. The dose of risperidone may need to be titrated accordingly for patients receiving carbamazepine,
particularly during initiation or discontinuation of carbamazepine therapy. Co-administration of other known enzyme
inducers (e.g., phenytoin, rifampin, and phenobarbital) with risperidone may cause similar decreases in the combined
plasma concentrations of risperidone and 9-hydroxyrisperidone, which could lead to decreased efficacy of risperidone
Fluoxetine and Paroxetine
Fluoxetine (20 mg QD) and paroxetine (20 mg QD) have been shown to increase the plasma concentration
of risperidone 2.5-2.8 fold and 3-9 fold respectively. Fluoxetine did not affect the plasma concentration of
9-hydroxyrisperidone. Paroxetine lowered the concentration of 9-hydroxyrisperidone an average of 13%. When either
concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re-evaluate the dosing of
RISPERDAL®. The effects of discontinuation of concomitant fluoxetine or paroxetine therapy on the
pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied.
Repeated oral doses of risperidone (3 mg BID) did not affect the exposure (AUC) or peak plasma
concentrations (Cmax) of lithium (n=13). Valproate Repeated oral doses of risperidone (4 mg QD) did not
affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided
doses) compared to placebo (n=21). However, there was a 20% increase in valproate peak plasma concentration
(Cmax) after concomitant administration of risperidone.
RISPERDAL® (0.25 mg BID) did not show a clinically relevant effect on the
pharmacokinetics of digoxin.
Drugs That Inhibit CYP 2D6 and Other CYPIsozymes
Risperidone is metabolized to 9-hydroxyrisperidone by CYP 2D6, an enzyme that is polymorphic in the
population and that can be inhibited by a variety of psychotropic and other drugs. Drug interactions that reduce the
metabolism of risperidone to 9-hydroxyrisperidone would increase the plasma concentrations of risperidone and lower
the concentrations of 9-hydroxyrisperidone. Analysis of clinical studies involving a modest number of poor
metabolizers (n 70) does not suggest that poor and extensive metabolizers have different rates of adverse effects. No
comparison of effectiveness in the two groups has been made.
In vitro studies showed that drugs metabolized by other CYPisozymes, including 1A1, 1A2, 2C9,
2C19, and 3A4, are only weak inhibitors of risperidone metabolism. There were no significant interactions between
risperidone and erythromycin.
Drugs Metabolized by CYP 2D6
In vitro studies indicate that risperidone is a relatively weak inhibitor of CYP 2D6.
Therefore, RISPERDAL® is not expected to substantially inhibit the clearance of drugs that are
metabolized by this enzymatic pathway. In drug interaction studies, risperidone did not significantly affect the
pharmacokinetics of donepezil and galantamine, which are metabolized by CYP 2D6.