Atypical (Second-generation) Antipsychotic — Active Metabolite of Risperidone Pregnancy: Use only if benefit outweighs risk — neonatal EPS and withdrawal. Depot cannot be removed if adverse effects occur.

Paliperidone

Brand names: Invega (oral), Xeplion (monthly IM depot), Trevicta (3-monthly IM depot)

Adult dose

Dose: Oral (Invega): 6mg OD in morning initially; usual range 6–12mg OD; maximum 12mg OD. IM depot (Xeplion): 150mg IM deltoid on day 1, 100mg IM deltoid on day 8, then 75mg IM deltoid or gluteal monthly (adjust 25–150mg based on response).

Route: Oral (extended-release) / IM depot (monthly or 3-monthly)

Frequency: Once daily (oral); monthly (Xeplion); 3-monthly (Trevicta)

Max: 12mg OD (oral); 150mg/month (Xeplion depot)

Active metabolite of risperidone. Extended-release oral formulation — tablet shell excreted intact (warn patients). Depot formulation improves adherence — Xeplion requires no oral run-in if tolerability to oral risperidone/paliperidone established. Cannot be used in severe renal impairment (renally excreted, like amisulpride).

Paediatric dose

Route: Oral

Frequency: Once daily

Max: 12mg OD

Invega oral licensed from age 12 years for schizophrenia. Seek specialist child and adolescent psychiatry opinion.

Dose adjustments

Renal

eGFR 50–80: maximum 6mg OD (oral); 75mg/month (depot). eGFR 10–49: maximum 3mg OD (oral); depot not recommended. eGFR <10: avoid.

Hepatic

No dose adjustment required for mild-moderate hepatic impairment — minimal hepatic metabolism.

Clinical pearls

Paliperidone extended-release tablet: the tablet shell is excreted intact — patients may see the empty tablet in their stool. Counsel them that this is expected and does not mean the drug was not absorbed (osmotic pump delivery system)
Xeplion depot: requires initiation schedule (150mg D1, 100mg D8) — initiates a therapeutic level rapidly. Good option when adherence is the primary concern
Renally excreted — like amisulpride, dose adjustment mandatory in CKD (unusual for antipsychotics)
Compared to risperidone: paliperidone ER has less first-pass variability, less CYP2D6 interaction burden, simpler metabolism

Contraindications

Severe renal impairment (eGFR <10)
Hypersensitivity to paliperidone or risperidone
QTc prolongation

Side effects

Hyperprolactinaemia (prominent — as per risperidone)
EPSE (akathisia, parkinsonism)
QTc prolongation
Insomnia, agitation
Weight gain (less than olanzapine/quetiapine)
Orthostatic hypotension
Injection site pain (depot)

Interactions

QT-prolonging drugs — additive risk
Carbamazepine, rifampicin — CYP induction reduces paliperidone levels; increase dose
Levodopa — antagonism

Monitoring

ECG (QTc)
Prolactin level (if symptoms)
eGFR (dose adjustment)
EPSE assessment
Weight and metabolic parameters
Injection site (depot)

Reference: BNFc; BNF 90; NICE CG178 (Psychosis and Schizophrenia). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways