risperidone
atypical antipsychotic· Brands: Risperdal, Risperdal Consta, Risperdal M-TabIMPO
Mechanism of action
Risperidone is an atypical antipsychotic that acts as a dopamine D2 and serotonin 5-HT2A receptor antagonist. Its antipsychotic effect is thought to involve D2 antagonism in mesolimbic pathways, while 5-HT2A blockade may reduce extrapyramidal side effects and improve negative symptoms. It also has affinity for alpha1 adrenergic and histamine H1 receptors, contributing to its adverse effect profile.
Pharmacokinetics
Risperidone is well absorbed orally and undergoes extensive hepatic metabolism via CYP2D6 to its active metabolite, 9-hydroxyrisperidone (paliperidone). The parent drug and metabolite are pharmacologically similar. Elimination is primarily renal, with a half-life of about 3 hours for risperidone and 24 hours for the active moiety. Steady-state is reached within 5 days.
Indications & dosing
Schizophrenia
Start at 2 mg daily and titrate in steps of 2 mg every 2 to 3 days. Usual maintenance range 4 to 8 mg daily.
- adult · PO: 2–8 mg once daily · Start at 2 mg daily and titrate in steps of 2 mg every 2 to 3 days. Usual maintenance range 4 to 8 mg daily.
Bipolar mania
For acute manic episodes, initiate at 2 to 3 mg daily, titrate in steps of 1 to 2 mg daily.
- adult · PO: 2–6 mg once daily · For acute manic episodes, initiate at 2 to 3 mg daily, titrate in steps of 1 to 2 mg daily.
Irritability associated with autistic disorder
Initial dose is weight based: 0.25 mg daily if <20 kg, 0.5 mg daily if ≥20 kg. Titrate slowly in increments of 0.25 to 0.5 mg at intervals of at least 1 week.
- pediatric · PO: 0.25–1.5 mg once daily · Initial dose is weight based: 0.25 mg daily if <20 kg, 0.5 mg daily if ≥20 kg. Titrate slowly in increments of 0.25 to 0.5 mg at intervals of at least 1 week.
Contraindications & precautions
- Known hypersensitivity to risperidone or paliperidone · Cross-reactivity may occur.
- Significant cardiovascular disease, e.g. heart failure, bradycardia, or hypokalaemia · Risperidone can cause QT prolongation and orthostatic hypotension; use with caution.
- Elderly patients with dementia-related psychosis · Increases risk of cerebrovascular events and all-cause mortality.
- Use with caution in elderly patients with dementia, as there is an increased risk of cerebrovascular events and mortality.
- Monitor blood pressure for orthostatic hypotension, especially during dose titration and in elderly or debilitated patients.
- Use with caution in patients with a history of QT prolongation, bradycardia, or concurrent use of QT-prolonging drugs.
- Taper the dose slowly when discontinuing to avoid withdrawal symptoms or rebound psychosis.
- Monitor for signs of hyperprolactinaemia, which may cause galactorrhoea, amenorrhoea, or infertility.
Adverse effects
- Extrapyramidal symptoms (e.g. pseudoparkinsonism, dystonia)
- Sedation / somnolence
- Weight gain
- Orthostatic hypotension
- Hyperprolactinaemia (symptoms: galactorrhoea, menstrual disturbance)
- QT prolongationserious
- Neuroleptic malignant syndromeserious
- Tardive dyskinesiaserious
Interactions
- fluoxetinemajorIf co-prescription is necessary, consider reducing the risperidone dose and monitor for signs of extrapyramidal symptoms, sedation, and hypotension. Monitor blood pressure and ECG if risk factors for QT prolongation. When discontinuing fluoxetine, risperidone levels may fall, requiring dose adjustment. Consider alternative antidepressants with less CYP2D6 inhibition.
Renal & hepatic adjustment
- eGFR 30–59: Start with 0.5 mg twice daily, titrate cautiously. Consider reducing the maintenance dose by half.
- eGFR 0–29: Start with 0.5 mg once daily, titrate very slowly. Use with caution and monitor renal function.
- Hepatic impairment (mild): No dosage adjustment usually required. Use with caution.
- Hepatic impairment (moderate): Start with 0.5 mg twice daily, titrate slowly. Reduce maintenance dose if necessary.
- Hepatic impairment (severe): Use with caution. Consider starting at 0.5 mg once daily and titrate very slowly. No specific dose recommended.
Monitoring, pregnancy & toxicity
- Blood pressure (sitting and standing) · Baseline and regularly during titration
- Extrapyramidal symptoms (rigidity, tremor, akathisia) · During dose titration and with any dose change
- Weight and BMI · Baseline and periodically
- Blood glucose and lipid profile · Baseline and periodically, especially in those with risk factors
- Prolactin levels · If symptoms of hyperprolactinemia (galactorrhea, amenorrhea)
- ECG (QT interval) · Baseline in those with risk factors, and following dose increases
- Pregnancy: Risperidone should be used during pregnancy only if the expected benefit justifies the potential risk. If used in the third trimester, monitor the neonate for extrapyramidal or withdrawal symptoms.
- Toxicity: Extrapyramidal symptoms (acute dystonia, parkinsonism, akathisia) · Reduce dose or switch to another antipsychotic. Administer anticholinergic agent (e.g., procyclidine) for acute dystonia.
- Toxicity: Hypotension and tachycardia · Supportive care: place patient supine, give IV fluids, monitor blood pressure and heart rate.
- Toxicity: QT prolongation · Monitor ECG, correct electrolyte abnormalities, discontinue risperidone if severe or symptomatic.
- Toxicity: Sedation and central nervous system depression · Supportive care: ensure airway, monitor vital signs, consider activated charcoal if recent ingestion.
Clinical notes
Risperidone is used for schizophrenia, bipolar mania, and irritability associated with autistic disorder. It is available in oral and long-acting injectable formulations. Doses are titrated gradually to reduce extrapyramidal symptoms. Common adverse effects include weight gain, metabolic changes, hyperprolactinaemia, and orthostatic hypotension. Caution is needed in the elderly and those with cardiovascular disease. Monitor blood pressure and prolactin levels. Long-acting formulations require a lag period before full effect; oral cover may be needed initially.
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BNF; local formulary