risperidone

General Information

Risperidone (brand Risperdal and numerous generics) is a second-generation antipsychotic available in oral, orally disintegrating, solution, and long-acting injectable forms for schizophrenia, bipolar disorder, and irritability in autism.

This profile highlights schizophrenia, bipolar I mania/mixed episodes, and long-acting injectable maintenance where predictable dosing and depot options are valuable.

Risperidone mechanism of action centres on serotonin-dopamine antagonism with active metabolite paliperidone, enabling once-daily and long-acting strategies when cross-titrated thoughtfully.

The contrast view and the Risperidone evidence feed can help balance prolactin, metabolic, and LAI considerations alongside the bipolar disorder hub when planning mood disorder regimens.

Widely used due to efficacy and depot options, though clinicians monitor prolactin elevation, EPS, and weight gain. Often chosen for predictable oral-to-LAI conversions.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Risperidone antagonizes dopamine D2 receptors and serotonin 5-HT2A receptors, balancing psychosis control with mitigation of EPS compared to typical antipsychotics.

Additional antagonism at adrenergic α1/α2 and histamine H1 receptors contributes to hypotension and sedation, while minimal muscarinic activity limits anticholinergic effects.

• Antagonist at dopamine D2 receptors.
• Antagonist at serotonin 5-HT2A/5-HT7 receptors.
• Antagonist at adrenergic α1/α2 and histamine H1 receptors.
• Negligible muscarinic receptor affinity.

Metabolism and Pharmacokinetics

• Oral bioavailability approximately 70%; peak concentration ~1 hour after dosing; food has minimal effect.
• About 90% protein bound with modest volume of distribution (~1–2 L/kg).
• Metabolized primarily via CYP2D6 (and CYP3A4) to active metabolite 9-hydroxyrisperidone (paliperidone).
• Half-life ~3 hours for risperidone and ~21 hours for 9-hydroxyrisperidone; depot half-life 3–6 days.
• Eliminated mainly in urine (35–45% as unchanged/active metabolite) with remainder as metabolites in urine/feces.

Dosing and Administration

• Schizophrenia (adults): start 1–2 mg/day; increase by 1–2 mg/day to 4–6 mg/day (doses >6 mg/day increase EPS).
• Schizophrenia (adolescents): initiate 0.5 mg/day; titrate to 1–6 mg/day.
• Bipolar mania: start 2–3 mg/day; adjust by 1 mg increments to 2–6 mg/day; pediatric initiation 0.5 mg/day with gradual titration.
• Risperdal Consta LAI: 25 mg IM every 2 weeks with 3-week oral overlap; range 12.5–50 mg based on response.
• Renal/hepatic impairment: start 0.5 mg twice daily; titrate cautiously.
• Maximum recommended oral dose 16 mg/day; doses above 6 mg/day rarely add efficacy and markedly raise EPS/prolactin risk.

Adverse Effects

Interactions

• CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) increase exposure—consider dose reduction and monitor for EPS/prolactin effects.
• CYP3A4 inducers (carbamazepine, rifampin, St. John’s wort) decrease concentrations—may require higher doses with monitoring.
• Additive CNS depression with alcohol, benzodiazepines, opioids.
• May antagonize dopaminergic agents (levodopa); avoid in Parkinson’s disease.
• Use caution with antihypertensives due to additive hypotension.

Other Useful Information

• Implement routine metabolic monitoring (weight, fasting lipids, glucose) at baseline, 3 months, then annually.
• Short-term trial data: a 7-week double-blind study (n=60) reported greater BMI increase and more frequent appetite increase with risperidone than aripiprazole—ask about appetite early as a practical signal for metabolic risk.
• Split dosing or bedtime dosing may reduce daytime sedation and hypotension.
• Ensure oral tolerability before initiating LAI; follow manufacturer guidance for injection technique and oral overlap.
• Educate patients about prolactin-related symptoms and sexual/reproductive health effects.
• Use the LAI Navigator for depot planning and counseling when transitioning to Risperdal Consta or Perseris, and consult the Paliperidone profile when switching between parent and metabolite formulations.

References

1. RISPERDAL prescribing information — DailyMed (2025)
2. RISPERDAL CONSTA prescribing information — DailyMed (2025)
3. Assessing THE Metabolic Impact OF Aripiprazole Versus Risperidone IN THE Treatment OF Schizophrenia: A Randomized Double Blind Controlled Clinical Trial — BMC Psychiatry (2025)
4. Haddad2004 Hyperprolactinemia
5. Long Acting Injectable Risperidone: Efficacy AND Safety OF THE First Long Acting Atypical Antipsychotic — American Journal of Psychiatry (2003)
6. Acute AND Continuation Risperidone Monotherapy IN Bipolar Mania: Randomized Placebo Controlled Trials — European Neuropsychopharmacology (2005)
7. Risperidone in the treatment of schizophrenia — American Journal of Psychiatry (1994)