Atypical antipsychotic – active metabolite of risperidone
ATC code: N05AX13 (Paliperidone)
9-hydroxyrisperidone – the main active metabolite of risperidone, marketed as a separate drug. A D2 dopamine and 5-HT2A serotonin receptor antagonist. Compared with risperidone, more stable pharmacokinetics via OROS (osmotic release oral system) and long-acting injectables (Xeplion monthly, Trevicta every 3 months, Byannli every 6 months). Less CYP metabolism – suitable in hepatic disease. Predominantly renally excreted.
First line
First-line for schizophrenia per 2020 and NG178. Starting dose 6 mg once daily in the morning (OROS form – do not break), therapeutic range 3–12 mg. Long-acting injectables are the main advantage over risperidone: Xeplion (paliperidone palmitate) monthly, Trevicta every 3 months, Byannli every 6 months – convenient with adherence issues. The Huhn 2019 network meta-analysis showed efficacy comparable to risperidone; prolactin-related effects are similar.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Paliperidone is an antipsychotic, the active metabolite of risperidone. It is prescribed only for schizophrenia and schizoaffective disorder ( 2020 guidelines). For acute stress, paliperidone does not work: no clinical studies of such use exist. The drug has serious side effects: extrapyramidal symptoms (tremor, muscle stiffness), QT-interval prolongation, hyperprolactinemia, metabolic syndrome. In elderly patients with dementia, it increases mortality ( boxed warning). If paliperidone was prescribed for stress, consider seeking a second opinion.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Direct links to regulator labels. Open in a new tab.
Boxed warning
FDA boxed warning: increased mortality in elderly patients with dementia treated with atypical antipsychotics. Not for dementia-related psychosis.
T3 use carries neonatal extrapyramidal and withdrawal risk.
Moderate milk concentrations. Use during lactation cautiously with monitoring of infant sedation, weight gain, and extrapyramidal symptoms.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Paliperidone is evaluated for the following indications with varying evidence strength: Schizophrenia (evidence tier A), Stress and anxiety (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Paliperidone (≥ 1 in 100): Drowsiness, Hyperprolactinemia (galactorrhea, amenorrhea, sexual dysfunction), Weight gain, Extrapyramidal disorders, Orthostatic hypotension, Tachycardia. See the Safety section for uncommon and serious reactions.
FDA category C. T3 use carries neonatal extrapyramidal and withdrawal risk.
Moderate milk concentrations. Use during lactation cautiously with monitoring of infant sedation, weight gain, and extrapyramidal symptoms.
Paliperidone is contraindicated in: Paliperidone or risperidone hypersensitivity; Dementia in older adults; Parkinson's disease, Lewy body dementia; QT prolongation; Pregnancy – with caution. Full list in the Safety section.
FDA boxed warning: increased mortality in elderly patients with dementia treated with atypical antipsychotics. Not for dementia-related psychosis.