Introduction
Risperdal (risperidone) is an atypical antipsychotic medication belonging to the benzisoxazole class. Developed by Janssen Pharmaceuticals, it received FDA approval in 1993 and has since become a cornerstone in the treatment of various psychiatric conditions. As a second-generation antipsychotic, it offers efficacy comparable to traditional antipsychotics with a potentially improved side effect profile, particularly regarding extrapyramidal symptoms.
Mechanism of Action
Risperidone exerts its therapeutic effects through potent antagonism of serotonin 5-HT2A and dopamine D2 receptors. Its high 5-HT2A/D2 receptor binding ratio distinguishes it from first-generation antipsychotics and contributes to its atypical properties. Additional activity includes antagonism at α1-adrenergic, α2-adrenergic, and H1 histaminergic receptors. The drug's metabolite, 9-hydroxyrisperidone (paliperidone), possesses similar pharmacological activity, contributing to the overall clinical effect.
Indications
FDA-approved indications:
- Schizophrenia in adults and adolescents (age 13-17)
- Bipolar I disorder (acute manic or mixed episodes) as monotherapy or adjunctive therapy to lithium or valproate in adults and children (age 10-17)
- Irritability associated with autistic disorder in children and adolescents (age 5-16)
Off-label uses (with varying evidence):
- Behavioral and psychological symptoms of dementia (with caution)
- Treatment-resistant depression (as adjunctive therapy)
- Tourette's syndrome
- Other psychiatric conditions requiring antipsychotic intervention
Dosage and Administration
Schizophrenia:- Adults: Initial dose 2 mg/day, may increase to 4-8 mg/day (maximum 16 mg/day)
- Adolescents: Initial dose 0.5 mg/day, target range 3-6 mg/day
- Adults: Initial dose 2-3 mg/day, may increase to 1-6 mg/day
- Children: Initial dose 0.5 mg/day, target range 2.5-6 mg/day
- Children: Initial dose 0.25 mg/day (<20 kg) or 0.5 mg/day (≥20 kg), target range 0.5-3 mg/day
- Renal impairment: Reduce initial dose by 50% in severe impairment
- Hepatic impairment: Use caution, consider dose reduction
- Elderly: Start with 0.5 mg twice daily, increase gradually
- CYP2D6 poor metabolizers: Reduce dose by approximately 50%
Pharmacokinetics
Absorption: Completely absorbed after oral administration, unaffected by food. Absolute bioavailability is 70%. Peak plasma concentrations occur within 1-2 hours. Distribution: Volume of distribution is 1-2 L/kg. Plasma protein binding is approximately 90% (risperidone binds to albumin and α1-acid glycoprotein). Metabolism: Extensive hepatic metabolism primarily via CYP2D6 to 9-hydroxyrisperidone (active metabolite). CYP3A4 plays a minor role. Elimination: Terminal elimination half-life is approximately 20 hours (risperidone) and 24 hours (9-hydroxyrisperidone). Excretion primarily renal (70%) and fecal (14%).Contraindications
- Hypersensitivity to risperidone or any component of the formulation
- History of neuroleptic malignant syndrome with risperidone
- Concomitant use with drugs that prolong QT interval in patients with cardiac conditions
- Dementia-related psychosis in elderly patients (increased mortality risk)
Warnings and Precautions
Black Box Warnings:- Increased mortality in elderly patients with dementia-related psychosis
- Not approved for use in patients with dementia-related psychosis
- Cerebrovascular adverse events in elderly patients with dementia
- Neuroleptic malignant syndrome (monitor for hyperpyrexia, muscle rigidity, autonomic instability)
- Tardive dyskinesia (periodically reassess need for continued treatment)
- Metabolic changes (weight gain, hyperglycemia, dyslipidemia)
- Hyperprolactinemia (monitor for galactorrhea, amenorrhea, gynecomastia)
- Orthostatic hypotension (particularly during initial dose titration)
- Seizures (use caution in patients with seizure disorders)
- Dysphagia (aspiration risk)
- Cognitive and motor impairment (caution when operating machinery)
- Priapism (requires immediate medical attention)
- Body temperature regulation disturbances
Drug Interactions
Major interactions:- CYP2D6 inhibitors (fluoxetine, paroxetine): Increase risperidone concentrations
- CYP3A4 inducers (carbamazepine, rifampin): Decrease risperidone concentrations
- Other CNS depressants: Enhanced sedative effects
- Antihypertensive agents: Additive hypotensive effects
- Drugs that prolong QT interval: Increased risk of cardiac arrhythmias
- Levodopa and dopamine agonists: Antagonized effects
Adverse Effects
Common (≥10%):- Somnolence (15-30%)
- Parkinsonism (15-20%)
- Headache (10-15%)
- Insomnia (10-15%)
- Agitation (10-15%)
- Anxiety (10-15%)
- Weight gain
- Dizziness
- Constipation
- Nausea
- Dyspepsia
- Rhinitis
- Increased prolactin levels
- Akathisia
- Dystonia
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Seizures
- Diabetes mellitus
- Hyperglycemia
- Diabetic ketoacidosis
- Cerebrovascular events
- Venous thromboembolism
- Priapism
- Leukopenia/neutropenia
Monitoring Parameters
Baseline:- Complete medical and psychiatric history
- Physical examination with weight, height, BMI
- Vital signs (blood pressure, heart rate)
- Fasting blood glucose/HbA1c
- Lipid profile
- Prolactin level (if symptomatic)
- ECG (if cardiac risk factors present)
- Assessment for movement disorders
- Weight/BMI (monthly for first 3 months, then quarterly)
- Blood pressure (regularly, especially during titration)
- Fasting glucose and lipids (at 3 months, then annually)
- Symptom assessment for extrapyramidal symptoms
- Prolactin monitoring (if clinically indicated)
- Treatment response evaluation
- Adverse effect assessment
Patient Education
Key points to discuss:- Take medication as prescribed; do not stop abruptly
- May cause drowsiness—avoid driving or operating machinery until effects known
- Rise slowly from sitting/lying position to prevent dizziness
- Report any unusual movements, muscle stiffness, or fever immediately
- Monitor weight regularly and report significant changes
- Be aware of potential for increased blood sugar (report excessive thirst, urination)
- Avoid alcohol and other CNS depressants
- Use effective contraception (may affect menstrual cycles)
- Keep all follow-up appointments for monitoring
- Store at room temperature, away from moisture
- Elderly: Increased risk of falls, stroke, and mortality
- Pediatric: Monitor growth and development closely
- Pregnancy: Discuss risks/benefits with provider (Category C)
- Breastfeeding: Not recommended (excreted in human milk)
References
1. FDA Prescribing Information: Risperdal (risperidone) 2. Lehne, R. A. (2013). Pharmacology for Nursing Care. Elsevier Health Sciences 3. Stahl, S. M. (2013). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications 4. Kane, J. M., et al. (2003). Efficacy and safety of risperidone versus placebo in patients with schizophrenia. Journal of Clinical Psychopharmacology 5. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier 6. Marder, S. R., et al. (1994). The effects of risperidone on the five dimensions of schizophrenia. American Journal of Psychiatry 7. National Institute for Health and Care Excellence (NICE) guidelines 8. American Psychiatric Association Practice Guidelines
This monograph is for educational purposes only and does not replace professional medical advice. Always consult healthcare providers for personalized medical decisions.