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
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
Induces
Inhibits

Pharmacodynamics

Mechanism of Action

Risperidone has a very high 5-HT_2A/D₂ ratio (which means it has a higher affinity for 5-HT_2A receptors than for D₂ receptors).
Antagonism of D₂, 5-HT_2A, 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

Schizophrenia
Bipolar I disorder
Bipolar II disorder
Major depressive disorder (adjunctive treatment)
Obsessive-compulsive disorder
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)
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)

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

Neuroleptic malignant syndrome

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

Mechanism of Action of Risperidone

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.

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