Risperidone (Risperdal)

Class

Second-generation (atypical) antipsychotic

Mechanism

Antagonist at dopamine D2 and serotonin 5-HT2A receptors; also blocks alpha-1 adrenergic and histamine H1 receptors, contributing to sedation and orthostatic hypotension

FDA-Approved Use

Schizophrenia, bipolar disorder (acute manic or mixed episodes), irritability associated with autism spectrum disorder (ASD)

Off-Label Use

Augmentation in major depressive disorder (MDD), agitation and aggression in dementia, management of post-ictal psychosis in epilepsy, post-stroke affective lability, post-stroke aggression, agitation and aggression in neurodevelopmental conditions

Formulation

Oral tablets, orally disintegrating tablets (ODT), oral solution, long-acting injectable (Risperdal Consta)

Titration

0.25–0.5 mg p.o. daily, titrated slowly based on clinical response and tolerability

Dose Range

0.5–6 mg/day

Kinetics

Half-life ~3 hours (parent drug), active metabolite (9-hydroxyrisperidone) half-life ~20 hours; metabolized primarily via CYP2D6 and CYP3A4; steady state ~1–2 days

Common AEs

Sedation, weight gain, extrapyramidal symptoms (EPS), orthostatic hypotension, hyperprolactinemia, dizziness, fatigue

Serious/Rare AEs

Neuroleptic malignant syndrome (NMS), tardive dyskinesia, cardiac arrhythmias, leukopenia

Monitoring

Monitor weight, fasting glucose, lipids, prolactin levels, blood pressure, and EPS every 3–6 months

Black Box Warning

Increased risk of mortality in elderly patients with dementia-related psychosis

Considerations

Risperidone may be used short-term to manage psychotic symptoms following seizure clusters in post-ictal psychosis, typically at low doses. Caution is warranted in patients with Parkinson’s disease (PD), dementia (including AD and LBD), and elderly individuals due to increased risk of sedation and extrapyramidal symptoms. It may be cautiously used for short-term management of agitation or delusions following stroke, with careful fall risk assessment. Avoid use in patients highly sensitive to dopamine antagonism due to risk of severe EPS or prolactin elevation.