Risperidone (Risperdal)

Pharmacokinetics of Risperidone

Absorption
Distribution
Metabolism The active metabolite is paliperidone
Elimination
Half-life 26 hours, metabolite lasts 3-6 days

Risperidone: Cytochrome P450 Metabolism

Substrate of (Metabolized by) 2D6, 3A4
Induces
Inhibits
  • Risperidone has a very high 5-HT2A/D2 ratio (which means it has a higher affinity for 5-HT2A receptors than for D2 receptors).
  • Antagonism of D2, 5-HT2A, alpha 1, alpha 2, and H1 receptors
  • After risperidone is metabolized by the liver (via CYP 2D6), the primary active metabolite is 9-hydroxyrisperidone (paliperidone) which drives the primary clinical effect.

Dosing for Risperidone

Starting 0.5 mg to 1 mg (in elderly or children)
Titration
Maximum 16 mg
Taper Slow taper
  • Risperidone comes in both an oral and long-acting intramuscular (IM) formulation (Trade name: Risperdal Consta)
  • When starting a patient on Risperdal Consta IM, it takes 21 days for the IM medication to fully take effect due to the delayed of the risperidone microspheres
    • Risperdal Consta thus requires 21 days' oral supplementation when starting treatment because release is delayed for up to 3 weeks 
  • Intramuscular risperidone 25mg is equivalent to about 2 to 3 mg oral risperidone (approximately)
  • Consta also requires refrigeration, unlike paliperidone IM (Invega) which can be stored at room temperature
  • Concomitant administration of risperidone with fluoxetine may increase the plasma concentration of risperidone by 2-3 fold.[1]
    • This is because fluoxetine is a CYP 2D6 inhibitor, and risperidone is a 2D6 substrate
  • Risperidone at higher doses (6-8mg) acts more like a high potency first-generation anti-psychotic. There is a dose-responsive relationship with dose and incidence of EPS.[2]
  • In severe renal and hepatic impairment, a lower starting dose of 0.5 mg BID should be used. May increase to dosages above 1.5 mg twice daily at intervals of one week or longer