Sperdal

Approved Uses:

• Schizophrenia: Adults and adolescents (13–17 years) for the treatment of schizophrenia.
• Bipolar I Disorder—Mania/Mixed Episodes: Adults and pediatric patients (10–17 years), as monotherapy or adjunctive to lithium or valproate.
• Irritability in Autism Spectrum Disorder: Children and adolescents (5–16 years) presenting with aggression, self-injury, or tantrums.

Important Off‑Label Uses:

• Schizoaffective Disorder (psychotic and mood symptoms)
• Behavioral Disturbances in Dementia (used with caution)
• Tourette’s Syndrome
• Adjunct in Severe Conduct Disorder or OCD (when standard therapies fail)

Formulations: Oral tablets, orally disintegrating tablets (ODT), and oral solution.

Adults:

• Schizophrenia: Start 1 mg twice daily; increase to 2 mg BID on Day 2, then up to 4–8 mg total daily in 1–2 doses; maximum 16 mg/day.
• Bipolar Mania: Start 2–3 mg once daily; maintenance dosage is 1–6 mg/day.

Elderly or those with comorbidities:

• Initiate at 0.5 mg BID; titrate slowly, monitoring blood pressure and EPS.

Pediatrics:

• Schizophrenia (13–17 yrs): Start 0.5 mg once daily; titrate to 3 mg/day.
• Bipolar Mania (10–17 yrs): Start 0.5 mg/day; target 1–6 mg/day.
• Autistic Irritability (5–16 yrs):
• <20 kg: Start 0.25 mg/day
• ≥20 kg: Start 0.5 mg/day
• Titrate up to 2.5 mg/day.

Renal or Hepatic Impairment:

• Begin at 0.5 mg BID; titrate cautiously with close monitoring.

Risperidone is a second-generation (atypical) antipsychotic that functions primarily as an antagonist at dopamine D₂ and serotonin 5‑HT₂A receptors. It also binds to α₁-adrenergic and H₁-histamine receptors, and to a lesser extent 5‑HT₁A and α₂-adrenergic receptors. Dopamine antagonism helps reduce psychotic symptoms, while serotonin antagonism addresses negative symptoms and reduces extrapyramidal side effects. Additional receptor blockade contributes to mood stabilization and behavior modulation.

• Absorption: Rapidly absorbed; peak levels reached in 1–2 hours.
• Bioavailability: ~70% (oral).
• Distribution: ~90% plasma protein bound; widely distributed.
• Metabolism: Primarily via CYP2D6 to active metabolite 9‑hydroxyrisperidone (paliperidone).
• Half-Life:
• Risperidone: 3–20 hours (varies by CYP2D6 status)
• 9‑Hydroxyrisperidone: ~21–30 hours
• Elimination: ~70% via kidneys, ~14% via feces.

• Pregnancy (Category C): Possible neonatal EPS or withdrawal symptoms if exposed during third trimester. Use only if clearly necessary.
• Breastfeeding: Excreted in breast milk. Monitor infants for sedation, feeding difficulties, or extrapyramidal signs. Exercise caution—consider alternatives.

• Primary Class: Atypical (Second‑Generation) Antipsychotic
• Subclass: Benzisoxazole derivative

• Hypersensitivity to risperidone or similar compounds
• Severe CNS depression
• History of neuroleptic malignant syndrome
• Not approved for elderly patients with dementia-related psychosis due to increased mortality risk

• Increased mortality in elderly dementia patients—use is contraindicated.
• Neuroleptic Malignant Syndrome (NMS): Monitor for fever, rigidity, altered consciousness.
• Tardive Dyskinesia: Risk increases with long-term use—assess regularly.
• Orthostatic Hypotension: Particularly in volume-depleted or elderly patients; monitor BP.
• Metabolic Effects: Monitor weight, blood glucose, lipids (risk of hyperglycemia and dyslipidemia).
• Hematologic: Monitor CBC for leukopenia, neutropenia, eosinophilia.
• Seizures/Prolactin Increase: Use caution in susceptible individuals.

Common:

• CNS: Somnolence, insomnia, dizziness, anxiety, headache
• GI: Nausea, vomiting, constipation, increased appetite
• Endocrine: Elevated prolactin—galactorrhea, amenorrhea, gynecomastia
• Metabolic: Weight gain, hyperglycemia
• Neurological: EPS—tremor, rigidity, akathisia

Serious:

• NMS, tardive dyskinesia, QT prolongation, orthostatic hypotension, seizures, agranulocytosis, suicidal ideation (especially in children/adolescents)

Onset & Severity:

• EPS generally appear early; metabolic changes develop over weeks to months

• CYP2D6 Inhibitors (e.g., fluoxetine): Increase risperidone levels
• CYP3A4 Inducers (e.g., carbamazepine): Reduce effectiveness
• CNS Depressants: Additive sedation with alcohol, benzodiazepines
• Antihypertensives: Additive hypotensive effects
• Dopaminergics: Antagonistic interaction reduces effect of levodopa
• QT-Prolonging Agents: Increased risk of arrhythmias

• FDA & EMA: Reinforced boxed warning on dementia-related mortality risk.
• Monitoring Recommendations: Updated on metabolic parameters (weight, glucose, lipids).
• Clinical Guidelines: Risperidone remains first-line for schizophrenia, bipolar mania, and autistic irritability; recommended by APA and NICE.

• Temperature: Store at 20–25 °C (68–77 °F); transient excursions between 15–30 °C acceptable.
• Humidity & Light: Protect from moisture and excessive light.
• Handling: Keep oral solution in original bottle until use; stable for 6 weeks after opening.
• Refrigeration: Not necessary.
• ODT Formulations: Handle with dry hands and avoid splitting.