Risperidone (oral)

Class

Second Generation Antipsychotic

Neuroscience-based Nomenclature (NbN)

Pharmacological Target

Dopamine, serotonin, norepinephrine

Mode of Action

Receptor Antagonist (D2, 5-HT2, NE alpha-2)

Brand Name

Risperdal

Monograph

Monograph Link

Adverse Effects

  Weight gain very common
  Sedation common
  Sexual dysfunction common
  Agitation
  Anxiety
  Extrapyramidal symptoms
  Headache
  Insomnia

Serious/Life-Threatening AEs

  Tachycardia, and rare cares or cardiac arrhythmias and first-degree atrioventricular block
  Rare cases of serious hyperglycemia, including diabetic ketoacidosis and death
  Increased mortality rate vs. placebo when used in elderly patients with dementia
  Rare cases of neuroleptic malignant syndrome
  Rare venous thromboembolism

Other

  Increased mortality rates vs. placebo have been observed in elderly patients with dementia, particularly those on furosemide. Use of risperidone should not be used in this population.
  Use with caution in patients with cardiovascular or cerebrovascular disease or other conditions that would predispose them to hypotension
  Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold
  Metabolic parameters should be regularly monitored in all patients
  As with all antipsychotics, there is a risk for extrapyramidal side effects and tardive dyskniesia

Bioavailability (Oral)

70%

Volume of distribution (Vd)

1-2 L/Kg

Protein binding

  Risperidone: 88-90%
  9-hydroxyrisperidone (active metabolite): 77%

Elimination half-life (Oral)

  Extensive Metabolizers: Risperidone: 3 hours; 9-hydroxyrisperidone (active metabolite): 21 hours
  Poor Metabolizers: Risperidone: 20 hours; 9-hydroxyrisperidone (active metabolite): 30 hours

Time to peak (Tmax)

  Risperidone: 1 hour
  9-hydroxyrisperidone (active metabolite): 3 hours

Metabolism

  Risperidone: primarily CYP2D6. CYP3A4 (limited)
  9-hydroxyrisperidone (active metabolite): limited via CYP2D6 and CYP3A4

Excretion

  Urine: 70% (9-hydroxyrisperidone represents 35-45% of dose)
  Feces: 14%

Special Populations

  Renal impairment: use lower dosages
  Hepatic impairment: use lower dosages
  Cardiac impairment: use with caution
  Elderly: use with caution
  Children and adolescents: safety and efficacy in children less than 18 years have not been evaluated

Other Potential Benefits

  Antipsychotic
  Augmentation of antidepressant effect in major depressive disorder
  Augmentation of antidepressant in OCD
  Autism spectrum disorders
  Dementia

Potential for Other Drugs to Affect Risperidone

  Risperidone is mainly metabolized through CYP2D6, and to a lesser extent through CYP3A4. Both risperidone and its active metabolite 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp). Substances that modify CYP2D6 activity, or substances strongly inhibiting or inducing CYP3A4 and/or P-gp activity, may influence the pharmacokinetics of the risperidone active antipsychotic fraction.
  Strong CYP2D6 Inhibitors: Co-administration of risperidone with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active antipsychotic fraction (risperidone and 9-hydroxyrisperidone combined). Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active antipsychotic fraction (e.g., paroxetine). When concomitant paroxetine or another strong CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
  CYP3A4 and/or P-gp Inhibitors: Co-administration of risperidone with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active antipsychotic fraction. When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
  CYP3A4 and/or P-gp Inducers: Co-administration of risperidone with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active antipsychotic fraction. When concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.

Potential for risperidone to affect other drugs

  Risperidone is a CYP2D6 and CYP3A4 substrate. Studies found that risperidone did not affect the pharmacokinetics of the following: aripiprazole, lithium, valproate, and digoxin.