Risperidone

RISPERDAL

What it isD2 and broad serotonin-receptor antagonist; schizophrenia, bipolar mania, and irritability in autism.

Why this oneIts active metabolite is paliperidone, and its oral and long-acting formulations make continuity unusually flexible.

What limits itProlactin rises more than with any other second-generation agent; extrapyramidal effects become prominent as dose rises.

FDA-approved for

BOXED WARNING Increased mortality in elderly patients with dementia-related psychosis; not approved for dementia-related psychosis.

FDA dosing	Population	Start	Target	Max
Schizophrenia	Adults	2 mg/day (QD or BID)	4-8 mg/day	16 mg/day
Schizophrenia	Adolescents 13-17 yr	0.5 mg QD	3 mg/day	6 mg/day
Bipolar mania	Adults	2-3 mg/day	1-6 mg/day	6 mg/day
Bipolar mania	Children/adolescents 10-17 yr	0.5 mg QD	1-2.5 mg/day	6 mg/day
Irritability associated with autistic disorder	Pediatric >=5 yr	0.25 mg/day (<20 kg) or 0.5 mg/day (>=20 kg)	0.5 mg/day (<20 kg) or 1 mg/day (>=20 kg)	3 mg/day

Titration Schizophrenia/bipolar: increase at intervals >=24 h; autistic disorder irritability: increase at intervals >=2 weeks

Renal Severe (CrCl <30 mL/min): start 0.5 mg BID; increase in <=0.5 mg BID increments, intervals >=1 week for doses above 1.5 mg BID

Hepatic Severe (Child-Pugh 10-15): start 0.5 mg BID; titrate as in severe renal impairment

Oral solution taken directly from calibrated syringe or mixed with water, coffee, orange juice, or low-fat milk (not cola or tea)
M-TAB orally disintegrating tablet: place on tongue immediately after opening blister; do not split or chew
With strong CYP2D6 inhibitors (fluoxetine, paroxetine) reduce dose; do not exceed 8 mg/day in adults
With enzyme inducers (e.g., carbamazepine) up to double the usual dose; adjust when inducer is stopped

Cerebrovascular events, including stroke, in elderly patients with dementia-related psychosis
Neuroleptic malignant syndrome
Tardive dyskinesia
Metabolic changes: hyperglycemia/diabetes, dyslipidemia, weight gain
Hyperprolactinemia
Orthostatic hypotension
Leukopenia, neutropenia, agranulocytosis
Cognitive and motor impairment
Seizures

Pregnancy No established drug-associated risk of major birth defects; third-trimester exposure risks neonatal extrapyramidal/withdrawal symptoms.

Lactation Present in human milk (relative infant dose 2.3-4.7%); monitor infant for sedation, EPS, failure to thrive, jitteriness.

⚠ BOXED WARNING

Cost, est. cash$300–$5,000/dose or month

Generic entry2008

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability2 / 4

Sedation liability2 / 4

QT / Torsades1 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityMetabolic effects, extrapyramidal symptoms/tardive dyskinesia and agent-specific QT or orthostatic risk.

CYP2D6 substrate

CYP3A4 substrate