Paliperidone
Invega · INVEGA SUSTENNA
Second-Generation AntipsychoticGeneric availableTDM data
Paliperidone palmitate is hydrolyzed to paliperidone . Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone is unclear. However, the drug's therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2A ) receptor antagonism.
Compare Paliperidone →FDA-Approved Indications
- Schizophrenia (adults)
- Schizoaffective disorder — mono or adjunct to mood stabilizers/antidepressants (adults)
Common Off-Label Uses
- Bipolar disorder
- Agitation in dementia (limited direct evidence; extrapolated from risperidone data)
What Sets This Drug Apart
- Active metabolite of risperidone (9-OH-risperidone) with minimal hepatic CYP metabolism — 59% excreted unchanged in urine; advantage when CYP2D6/3A4 interactions are a concern
- Highest prolactin elevation of any SGA in NMA data (mean 44-48 ng/mL vs placebo, exceeding even risperidone); persistent on chronic dosing
- Only SGA FDA-approved for schizoaffective disorder (both as monotherapy and adjunctive to mood stabilizers/antidepressants)
- Available as monthly (Sustenna), quarterly (Trinza), and 6-monthly (Hafyera) long-acting injectables — the longest-interval LAI options among SGAs
- OROS extended-release oral tablet carries a GI narrowing warning (non-deformable shell); LAI forms do not carry this warning
- Contraindicated in moderate-to-severe renal impairment (CrCl <50 mL/min) due to predominantly renal elimination
Boxed Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated wi