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risperidone

Brand: Risperdal, Risperdal Consta, Perseris

⚠ BBW Beers Criteria Prototype Drug
Drug Class: antipsychotic
Drug Family: antipsychotic
Subclass: atypical antipsychotic / second-generation
Organ Systems: cns

Mechanism of Action

Antagonizes D2 and 5-HT2A receptors; 5-HT2A antagonism modulates dopamine release in the nigrostriatal and mesocortical pathways, reducing EPS risk compared to typicals while maintaining antipsychotic efficacy; also blocks alpha-1, H1, and alpha-2 receptors.

dopamine D2 receptorsserotonin 5-HT2A receptors

Indications

  • schizophrenia
  • bipolar I mania
  • irritability associated with autism spectrum disorder
  • acute agitation (IM formulation)

Contraindications

  • dementia-related psychosis (black box)

Adverse Effects

Common

  • hyperprolactinemia (highest among atypicals due to D2 affinity)
  • weight gain
  • sedation
  • EPS (dose-dependent)
  • metabolic syndrome

Serious

  • tardive dyskinesia
  • NMS
  • QTc prolongation
  • orthostatic hypotension
  • hyperglycemia
  • cerebrovascular events in elderly

Pharmacokinetics (ADME)

Absorption Well absorbed; bioavailability ~70%
Distribution Protein binding 90%; Vd 1–2 L/kg
Metabolism CYP2D6 to active 9-hydroxyrisperidone (paliperidone); CYP2D6 poor metabolizers have higher risperidone levels
Excretion Renal (~70%); dose adjustment needed for CrCl <30 mL/min
Half-life 3 hours (risperidone) + 21 hours (9-OH-risperidone); effective half-life ~20 hours
Onset Days to weeks for full effect
Peak 1–2 hours
Duration 24 hours
Protein Binding 90%
Vd 1–2 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
CYP2D6 inhibitors (fluoxetine, paroxetine) increase risperidone/decrease 9-OH metabolite levels moderate
carbamazepine CYP3A4 induction reduces risperidone levels major
QTc-prolonging agents additive QTc prolongation moderate

Nursing Considerations

  1. Monitor fasting glucose, lipid panel, weight, and waist circumference at baseline and every 3–6 months — metabolic syndrome screening is standard of care
  2. Monitor for hyperprolactinemia symptoms: galactorrhea, amenorrhea, gynecomastia — risperidone has the highest prolactin-elevating effect among atypical antipsychotics
  3. Assess orthostatic blood pressure, especially on initiation; educate patients to rise slowly
  4. For Risperdal Consta (biweekly IM): oral risperidone must overlap for 3 weeks after first injection while depot levels accumulate

Clinical Pearls

  • Paliperidone (Invega) is simply the active metabolite of risperidone — 9-hydroxyrisperidone — and bypasses CYP2D6 metabolism, making it useful when drug interactions or CYP2D6 genotype is a concern
  • Risperidone has the highest risk of hyperprolactinemia among atypical antipsychotics (comparable to typicals) because unlike quetiapine and clozapine, it maintains high D2 receptor occupancy at tuberoinfundibular dopamine neurons

Safety Profile

Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Acute Agitation (IM Formulation) Antipsychotic Bipolar I Mania Irritability Associated With Autism Spectrum Disorder Schizophrenia
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