Paliperidone

• Schizophrenia
• Schizoaffective Disorder
• Psychotic Disorders

Paliperidone is an atypical antipsychotic medication used to treat schizophrenia and schizoaffective disorder. As the active metabolite of risperidone, it offers similar efficacy with a potentially different side effect profile and the convenience of long-acting injectable formulations.

Mechanism of Action

Paliperidone's antipsychotic effects are primarily mediated through:

• Dopamine D2 receptor antagonism: Core mechanism for treating positive symptoms
• Serotonin 5-HT2A receptor antagonism: Contributes to improved tolerability and efficacy for negative symptoms

Additional receptor activities include:

• Alpha-1 adrenergic antagonism (contributes to orthostatic hypotension)
• Histamine H1 antagonism (contributes to sedation and weight gain)
• No significant anticholinergic activity

Available Formulations

Oral Extended-Release (Invega):

• Tablets: 1.5 mg, 3 mg, 6 mg, 9 mg
• Uses OROS osmotic delivery system; do not crush, chew, or divide

Long-Acting Injectable (Monthly - Invega Sustenna):

• 39 mg, 78 mg, 117 mg, 156 mg, 234 mg prefilled syringes

Long-Acting Injectable (Every 3 Months - Invega Trinza):

• 273 mg, 410 mg, 546 mg, 819 mg prefilled syringes
• Requires stabilization on monthly injection first

Long-Acting Injectable (Every 6 Months - Invega Hafyera):

• 1092 mg, 1560 mg prefilled syringes
• Requires stabilization on monthly injection first

Medical Uses

FDA-Approved Indications:

• Schizophrenia in adults and adolescents (12-17 years, oral only)
• Schizoaffective disorder as monotherapy or adjunct to mood stabilizers/antidepressants

Long-acting injectables improve adherence and reduce relapse risk in patients with schizophrenia.

Dosing Guidelines

Oral (Schizophrenia):

• Adults: 6 mg once daily in the morning; range 3-12 mg daily
• Adolescents: 3 mg once daily; may increase to 6-12 mg daily
• Maximum: 12 mg daily (adults), 12 mg daily (adolescents with weight ≥51 kg)

Monthly Injectable (Invega Sustenna):

• Initiation: 234 mg IM deltoid day 1, then 156 mg IM deltoid day 8
• Maintenance: 39-234 mg monthly (deltoid or gluteal)

Schizoaffective Disorder:

• Similar dosing to schizophrenia
• May use as monotherapy or with mood stabilizers

Important Safety Information

Black Box Warnings:

• Increased mortality in elderly patients with dementia-related psychosis
• Not approved for dementia-related psychosis

Contraindications:

• Known hypersensitivity to paliperidone or risperidone

Warnings and Precautions:

• Tardive dyskinesia
• Neuroleptic malignant syndrome
• QT prolongation
• Hyperprolactinemia
• Metabolic changes (weight gain, hyperglycemia, dyslipidemia)
• Orthostatic hypotension
• Leukopenia/neutropenia
• Seizures

Drug Interactions

• QT-prolonging drugs: Avoid combination
• Dopamine agonists (levodopa): Antagonistic effects
• Strong CYP3A4/P-gp inducers (carbamazepine, rifampin): May decrease paliperidone levels
• Antihypertensives: Additive hypotensive effects
• CNS depressants: Additive sedation

Note: Unlike risperidone, paliperidone has minimal CYP2D6 metabolism.

Special Populations

• Renal Impairment:
  • CrCl 50-79: Max 6 mg/day oral; adjust injectable accordingly
  • CrCl 10-49: Max 3 mg/day oral; injectable not recommended
  • CrCl <10: Not recommended
• Hepatic Impairment: No adjustment for mild to moderate; not studied in severe
• Pregnancy: May cause extrapyramidal symptoms in neonates
• Elderly: Start with lower doses; avoid in dementia-related psychosis