Drug reference

Risperidone

Atypical Antipsychotic · Antipsychotic

Also known as Risperdal, Risdone, Rispax, Zisper

START

Confirm schizophrenia, bipolar, or approved indication. Baseline prolactin, fasting glucose, lipid panel, weight, ECG if cardiac risk. Screen for EPS risk factors. Start 0.5-2 mg daily.

TYPICAL MAX

8 mg/day (schizophrenia). EPS risk increases dramatically >6 mg/day. Elderly: max 3 mg/day.

STOP IF

NMS, severe TD, stroke symptoms, agranulocytosis, priapism, severe hyperglycemia/DKA, pregnancy

WATCH

EPS (AIMS scale every 6 months), prolactin (if symptoms), weight/glucose/lipids (baseline, 12 weeks, then annually), orthostatic BP, movement disorders

CDSCO approvedSchedule HJan AushadhiATC N05AX08

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 23min · absorption onset
PEAK: 1.5h · 1-2 h (oral)
t½: 20h · ~3 h (parent); ~24 h (9-OH metabolite); combined ~20 h
DURATION: 1d · 24 h (daily or BID dosing)

EXCRETION

~70% urine (metabolites); CYP2D6 primary; CYP3A4 secondary

route + CYP

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

FDA PLLR: Limited human data. Neonatal extrapyramidal and/or withdrawal symptoms reported with third-trimester exposure. Use only if benefit clearly outweighs risk.

FDA category + note

Top interactionssee all 12 →

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Available in India

306 branded formulations and 193 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Risperidone is a benzisoxazole atypical antipsychotic that acts as a combined serotonin-dopamine antagonist. It has high affinity for 5-HT2A receptors (Ki = 0.16 nM), D2 receptors (Ki = 3.3 nM), alpha-1 adrenergic receptors, and H1 histamine receptors. The 5-HT2A/D2 affinity ratio >1 is characteristic of atypical antipsychotics and is thought to reduce extrapyramidal symptoms while maintaining antipsychotic efficacy. It also blocks alpha-2 adrenergic receptors and has moderate affinity for H1 receptors. Unlike clozapine or olanzapine, risperidone has minimal anticholinergic (M1) activity. Its active metabolite, 9-hydroxyrisperidone (paliperidone), contributes significantly to the pharmacological effect.

Indications

Schizophrenia — acute and maintenance treatmentBipolar I disorder — acute manic or mixed episodes (monotherapy or adjunct)Irritability associated with autistic disorder (pediatric)Bipolar maintenance (monotherapy or with lithium/valproate)Dementia-related behavioral disturbances (off-label — black box warning)Tourette syndrome (off-label)Aggressive behavior (off-label)Treatment-resistant OCD (augmentation — off-label)

Dosing

Adult: Schizophrenia: 2 mg PO daily initially; titrate by 1-2 mg/day at ≥24h intervals; target 4-8 mg/day; max 16 mg/day. Bipolar mania: 2-3 mg PO daily initially; target 1-6 mg/day. Elderly/psychosis: 0.5 mg PO BID initially; titrate slowly.
Pediatric: Autism irritability (5-16 years, ≥20 kg): 0.5 mg PO daily; titrate by 0.5 mg at ≥4-day intervals; target 1-2.5 mg/day. Schizophrenia (13-17 years): 0.5 mg PO daily; target 3 mg/day; max 6 mg/day.
Renal adjustment: Start 0.5 mg BID; titrate by ≤0.5 mg BID; max 1.5 mg BID (3 mg/day). Active metabolite (9-OH-risperidone) accumulates in renal impairment.
Hepatic adjustment: Start 0.5 mg BID; titrate slowly. Monitor for sedation and orthostatic hypotension.
Geriatric: Start 0.5 mg BID; max 3 mg/day. Increased risk of cerebrovascular events, falls, mortality. Beers Criteria: avoid for behavioral symptoms of dementia.
Max dose: 16 mg/day (adults); 6 mg/day (pediatric schizophrenia); 3 mg/day (elderly/renal impairment)

Pharmacokinetics

Onset

Antipsychotic effect: 1-2 weeks for symptom improvement; 4-6 weeks for full effect.

Peak effect

Oral: peak plasma at 1-2 hours. Oral solution: 1 hour. M-tab: 1 hour. IM long-acting: peak at 4-6 weeks.

Duration

24 hours (supports once- or twice-daily dosing).

Half-life

Risperidone: ~3 hours (rapid). 9-hydroxyrisperidone (paliperidone, active metabolite): ~24 hours. Combined effective half-life: ~20 hours.

Bioavailability

~70% (oral). Food does not significantly affect absorption.

Protein binding

~90% (bound to albumin and alpha-1-acid glycoprotein).

Metabolism

Extensive hepatic via CYP2D6 (hydroxylation to active 9-OH-risperidone/paliperidone — primary pathway) and CYP3A4 (N-dealkylation). CYP2D6 poor metabolizers have higher risperidone and lower 9-OH-risperidone levels, with increased side effects.

Excretion

Urine: ~70% (35-45% as 9-OH-risperidone, 10% as parent drug). Feces: ~14%.

Contraindications

Hypersensitivity to risperidone or paliperidone
Dementia-related psychosis (FDA black box warning — increased mortality)
Severe CNS depression or comatose states

Side effects

Common

Extrapyramidal symptoms (EPS — akathisia, parkinsonism, dystonia; dose-related, >6 mg/day)Hyperprolactinemia (galactorrhea, amenorrhea, sexual dysfunction, gynecomastia)Sedation, somnolenceOrthostatic hypotension, dizziness (alpha-1 blockade)Weight gainConstipationInsomnia, anxietyTachycardia

Serious

Neuroleptic malignant syndrome (NMS)
Tardive dyskinesia (TD)
Cerebrovascular events, stroke (elderly with dementia)
Hyperglycemia, diabetes mellitus, diabetic ketoacidosis
Agranulocytosis, neutropenia
Seizures (dose-dependent)
Priapism (rare)
QT prolongation (rare, at high doses)
Increased mortality in dementia-related psychosis (black box warning)

Pregnancy & lactation

Pregnancy

FDA PLLR: Limited human data. Neonatal extrapyramidal and/or withdrawal symptoms reported with third-trimester exposure. Use only if benefit clearly outweighs risk.

Lactation

Excreted in breast milk (infant dose ~2.3-4.7% of maternal weight-adjusted dose). May cause infant sedation, EPS, poor feeding. Avoid breastfeeding if possible.