Risperidone (Risperdal)

Primer

Risperidone (Trade name: Risperdal) is an antipsychotic in the atypical antipsychotic class commonly used in the treatment of schizophrenia, bipolar disorder, and major depressive disorder. It has indications for various others psychiatric disorders, including obsessive compulsive disorder and behavioural and psychological symptoms of dementia.

Pharmacokinetics

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

Pharmacodynamics

Mechanism of Action

  • 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.

Toxicity

Indications

Dosing

Dosing for Risperidone

Starting 0.5 mg to 1 mg (in elderly or children)
Titration
Maximum 16 mg
Taper Slow taper

Formulations

  • Risperidone comes in both an oral and long-acting intramuscular (IM) formulation (Trade name: Risperdal Consta)

Intramuscular (Long-Acting Injectable)

  • Can be administered via deep intramuscular (IM) deltoid or gluteal injection
  • 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

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

  • 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
  • Sertraline is a moderate CYP2D6 inhibitor and may increase levels of risperidone, but not the metabolite 9-hydroxyrisperidone.[2]

Side Effects

Adverse Events

Clinical Pearls

  • 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.[3]

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

Medically Ill

  • 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

Resources

References

1) Spina, E., Avenoso, A., Scordo, M. G., Ancione, M., Madia, A., Gatti, G., & Perucca, E. (2002). Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia: a clinically relevant pharmacokinetic drug interaction. Journal of clinical psychopharmacology, 22(4), 419-423.
2) Puangpetch, A., Vanwong, N., Nuntamool, N., Hongkaew, Y., Chamnanphon, M., & Sukasem, C. (2016). CYP2D6 polymorphisms and their influence on risperidone treatment. Pharmacogenomics and personalized medicine, 9, 131.
3) Kapur S, Remington G, Zipursky RB, Wilson AA, Houle S. The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. Life Sci. 1995;57(10):PL103-7.