- Last edited on February 25, 2022
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
See also article: Introduction to Pharmacology
Pharmacokinetics of Risperidone
Absorption | |
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Distribution | |
Metabolism | The active metabolite is paliperidone |
Elimination | |
Half-life | 26 hours, metabolite lasts 3-6 days |
See also article: Cytochrome (CYP) P450 Metabolism
Risperidone: Cytochrome P450 Metabolism
Substrate of (Metabolized by) | 2D6, 3A4 |
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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
- Major depressive disorder (adjunctive treatment)
- Behavioural and psychological symptoms of dementia, low doses should be used
- Autism spectrum disorder (agitation), low doses should be used
Dosing
Dosing for Risperidone
Starting | 0.5 mg to 1 mg (in elderly or children) |
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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)
See main article: Long-Acting Injectable Antipsychotics (LAIs)
- 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
See main article: Geriatric Pharmacology
Pediatric
See main article: Pediatric Pharmacology
Obstetric and Fetal
See main article: Obstetric and Fetal Pharmacology
Medically Ill
See main article: Psychotropic Dosing in the 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.