Generic Name

Risperidone

Brand Names

*Risperdal*) is a second‑generation (atypical) antipsychotic widely used for schizophrenia, bipolar disorder, and irritability associated with autism.

Mechanism

• Primary targets:
• D2/D3 dopamine receptors – Blockade reduces psychotic symptoms.
• 5‑HT2A serotonin receptors – Moderate blockade attenuates extrapyramidal side‑effects and enhances cognitive benefits.
• Secondary effects:
• Partial agonism at 5‑HT1A → contributes to anxiolytic and mood‑stabilizing properties.
• Alpha‑1 adrenergic antagonism → may cause orthostatic hypotension.
• Result: A balanced dopamine‑serotonin inhibition that lowers psychotic symptoms while minimizing motor side‑effects.

Pharmacokinetics

• Absorption: Oral bioavailability ~60 % (increases with food).
• Distribution: Lipophilic; highly protein‑bound (~80 %).
• Metabolism: Hepatic via CYP2D6 and CYP3A4 to active metabolite 9‑OH‑risperidone (depot effect).
• Elimination: Dual hepatic‑renal; half‑life 3–5 h (active metabolite 20–40 h).
• Drug interactions:
• CYP2D6 inhibitors ↑ plasma levels.
• CYP3A4 inhibitors/inducers affect metabolism.
• Strong CYP2D6 inhibitors (e.g., fluoxetine) may require dose adjustment.

Indications

• Schizophrenia – acute psychosis, maintenance therapy.
• Bipolar disorder – manic and mixed episodes (short‑term).
• Irritability in autism spectrum disorder (≥6 yrs old).
• Adjunctive therapy for other neuropsychiatric conditions (off‑label use).

Contraindications

• Absolute:
• Hypersensitivity to risperidone or its excipients.
• Known severe hepatic impairment (CYP2D6‑poor metabolizers).
• Relative:
• Severe cardiovascular disease (arrhythmias, QT prolongation).
• Pregnancy Category C (risk outweighs benefit).
• Elderly with dementia‑related psychosis – increased mortality.
• Warnings:
• Neuroleptic malignant syndrome (NMS).
• Extrapyramidal symptoms (EPS), tardive dyskinesia.
• Hyperprolactinemia → amenorrhea, galactorrhea.
• Metabolic syndrome: weight gain, dyslipidemia, hyperglycemia.
• Orthostatic hypotension.

Dosing

• Route: Oral; intramuscular depot not approved.
• Administration tips: Take with food if GI upset; avoid alcohol; monitor for orthostatic hypotension when initiating therapy.

Adverse Effects

Common (≥10 %):
• Akathisia, dizziness, somnolence, weight gain, sexual dysfunction, constipation, hyperprolactinemia.

Serious (≤1 %):
• NMS, acute dystonia, tardive dyskinesia, severe orthostatic hypotension, metabolic syndrome, QTc prolongation, pancreatitis.

Serious alerts:
• NMS: fever, rigidity, autonomic instability; treat with benzodiazepines or dantrolene.
• Tardive dyskinesia: irreversible; consider dose reduction or switch.
• Pancreatitis: abdominal pain, vomiting, elevated lipase.

Monitoring

• Baseline: CBC, CMP, fasting glucose, lipid panel, weight, BMI, blood pressure, ECG (QTc).
• Ongoing:
• Weight/BMI every 2–4 weeks (first 3 months).
• Blood glucose monthly for first 3 months, then quarterly.
• Lipids every 6 months.
• Prolactin levels if amenorrhea or galactorrhea.
• Orthostatic vitals at initiation and 1‑week titration.
• Baseline and periodic ECG if QTc risk (e.g., concomitant QT‑prolonging drugs).

Clinical Pearls

• Depot effect: The active 9‑OH‑risperidone metabolite allows relatively stable plasma levels, facilitating smoother dose titration.
• CYP2D6 genotype: Poor metabolizers may experience higher exposure; consider dose reduction or monitor closely.
• Autism indication: Oral solution improves compliance in non‑verbal children; dosing based on weight (1–15 mg/m²).
• Weight gain mitigation: Pair with lifestyle counseling; switch to clozapine or olanzapine if metabolic syndrome overtakes clinical benefit.
• Drug‑drug interactions: Co‑administration with strong CYP3A4 inhibitors (ketoconazole) can elevate risperidone; monitor for EPS.
• Pregnancy: Risperidone is not recommended unless benefits outweigh risks; low placental transfer but potential neonatal withdrawal.
• Elderly: Use the lowest effective dose; monitor for mortality in dementia‑related psychosis, per FDA guidance.

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• References

1. FDA Drug Label, Risperidone.

2. Goodwin, G. & Jamison, K. *The American Psychiatric Pub.* 2024.

3. Cipriani A. et al. *Lancet Psychiatry*, 2022;9(4):295‑309.

4. Stahl, S. *Stahl's Essential Psychopharmacology*, 2024 edition.

*Note: Always verify local guidelines and individual patient factors before prescribing.*