Paliperidone (Invega, Invega Sustenna, Invega Trinza)

Class

Second-generation (atypical) antipsychotic

Mechanism

Active metabolite of risperidone; antagonizes dopamine D₂ and serotonin 5-HT₂A receptors; moderate affinity for α₁-adrenergic and histamine H₁ receptors

FDA-Approved Use

Schizophrenia, schizoaffective disorder

Off-Label Use

Augmentation in bipolar disorder, psychosis in dementia, management of behavioral dysregulation

Formulation

Oral extended-release tablets, long-acting injectable (Sustenna monthly, Trinza every 3 months)

Titration

Oral: 3 mg daily, titrated up to 6–12 mg daily as tolerated; Injectable: dosing per manufacturer protocol following oral stabilization

Dose Range

Oral 3–12 mg/day; injectable doses per standard intervals after stabilizatio

Kinetics

Primarily excreted unchanged renally; minimal hepatic metabolism; half-life approximately 23 hours (oral), extended with injectables

Common AEs

Extrapyramidal symptoms (EPS), insomnia, hyperprolactinemia, weight gain, metabolic changes including glucose dysregulation

Serious/Rare AEs

Increased prolactin levels may cause galactorrhea, sexual dysfunction, or gynecomastia; potential QT prolongation

Monitoring

Regular assessment for EPS, prolactin levels if clinically indicated, metabolic monitoring (weight, lipids, glucose), and periodic ECG in high-risk patients

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis

Considerations

Paliperidone’s long-acting injectable formulations are advantageous for patients with poor medication adherence, including those with intellectual disability or severe cognitive impairment. Monitor closely for EPS and prolactin-related side effects, especially in elderly patients and those with Parkinson’s disease.