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Paliperidone

  • Second-generation antipsychoticsSecond-generation antipsychotics

The active metabolite of risperidone, given as an extended-release tablet or a long-acting injection for schizophrenia and schizoaffective disorder.

Updated

Also called: 9-hydroxyrisperidone

Quick facts

Group
Second-generation antipsychotics
Target
Dopamine D2 and serotonin 5-HT2A receptors
Used for
Schizophrenia in adults and adolescents
Key effects
Restlessness · Sleepiness · Weight gain
Monitor
Weight · Movement disorders · Kidney function
ATC
N05AX13

No doses: the clinician sets them by the current guideline.

Mechanism of action

The figure shows risperidone in the human D2 receptor; paliperidone is risperidone with one added hydroxyl group and blocks the same site.

Target in 3D: Dopamine D2 and serotonin 5-HT2A receptors. PDB structure 6CM4 (RCSB PDB, public domain). View the structure at RCSB PDB

Paliperidone is 9-hydroxyrisperidone, the main active metabolite of risperidone. Like risperidone it blocks dopamine D2 receptors in the mesolimbic pathway, which reduces hallucinations and delusions, and blocks serotonin 5-HT2A receptors, which lessens extrapyramidal effects at usual doses. D2 block in the pituitary raises prolactin; alpha-1 and H1 block cause orthostatic dizziness and sedation.

  1. Blocks D2 receptors in mesolimbic pathways
  2. Blocks 5-HT2A receptors, easing motor side effects
  3. Positive psychotic symptoms decrease
  4. Pituitary D2 block raises prolactin

Indications

  • Schizophrenia in adults and adolescents Schizophrenia →
  • Schizoaffective disorder in adults

Adverse effects

Common

  • Restlessness (akathisia), stiffness, slow movement
  • Sleepiness, headache
  • Weight gain
  • Breast enlargement or discharge, missed periods, sexual problems (raised prolactin)
  • Dizziness on standing

Contraindications

  • Hypersensitivity to paliperidone or risperidone
  • Behavioural problems of dementia (not approved)

Key interactions

Other QT-prolonging drugs
Added QT prolongation.
CYP3A4/P-glycoprotein inducers (carbamazepine, rifampicin)
Lower paliperidone levels; the dose may need changing.
Alcohol and other CNS depressants
More drowsiness.

What is monitored

  • Weight, waist, glucose and lipids
  • Movement disorders (abnormal involuntary movements)
  • Prolactin-related symptoms
  • Kidney function; ECG when there are cardiac risks

Administration and safety

  • Extended-release tablet once daily in the morning, swallowed whole, never split, chewed or crushed.
  • The empty tablet shell may appear in the stool; this is expected.
  • Avoided in severe narrowing of the gut, because the tablet does not deform.
  • The long-acting injection is given intramuscularly by a health worker on a fixed schedule.

Pregnancy and breastfeeding

Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms; use weighs benefit and risk.

Nursing care

  • Before: record weight, blood pressure, glucose, lipids and kidney function.
  • During: watch for stiffness, restlessness, abnormal movements and fever.
  • Teach to rise slowly, avoid overheating and avoid alcohol.
  • Ask about breast changes, periods and sexual function.

Pharmacokinetics

Absorption
Extended-release tablet releases the drug through the day; also a monthly or longer-acting intramuscular injection (palmitate).
Elimination
The dose is reduced in kidney impairment; not recommended when kidney function is very low.

Test yourself

Think of the answer, then tap the question to see it.

What is the relationship between paliperidone and risperidone?

Paliperidone is 9-hydroxyrisperidone, risperidone's main active metabolite.

Why is paliperidone's dose reduced in kidney disease?

It is cleared mainly by the kidneys, so levels rise when kidney function falls.

Which hormone rises with paliperidone, and what symptoms follow?

Prolactin: breast enlargement or discharge, missed periods and sexual dysfunction.

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More Pharmacology questions →

Connections

← Back to the class: Second-generation antipsychotics

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Paliperidone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); PALIPERIDONE tablet, extended release (DailyMed (U.S. National Library of Medicine), 2026); Structure of the D2 Dopamine Receptor Bound to the Atypical Antipsychotic Drug Risperidone (RCSB Protein Data Bank, 2018); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.