What is the overview of paliperidone (Invega) for treating schizophrenia and other psychotic disorders?

Paliperidone Overview for Treating Schizophrenia and Psychotic Disorders

Paliperidone is an effective atypical antipsychotic medication for treating schizophrenia and schizoaffective disorder, with demonstrated efficacy for both positive and negative symptoms while offering the advantage of once-daily dosing and available long-acting injectable formulations. 1, 2

Mechanism of Action and Pharmacology

• Paliperidone (9-hydroxyrisperidone) is the major active metabolite of risperidone
• Primary mechanism: Antagonism of dopamine D2 and serotonin 5-HT2A receptors 3
• Available as extended-release oral tablets and long-acting injectable formulations
• Less extensive hepatic metabolism compared to most other antipsychotics 4
• Extended-release formulation allows for once-daily dosing without need for initial dose titration 4

FDA-Approved Indications

Paliperidone is FDA-approved for:

• Treatment of schizophrenia in adults and adolescents (ages 12-17) 2
• Treatment of schizoaffective disorder as monotherapy or adjunct to mood stabilizers/antidepressants 2

Dosing Recommendations

For Schizophrenia:

• Adults: Initial dose 6 mg/day; recommended range 3-12 mg/day; maximum 12 mg/day 2
• Adolescents:
  • Weight <51kg: Initial 3 mg/day; range 3-6 mg/day; maximum 6 mg/day 2
  • Weight ≥51kg: Initial 3 mg/day; range 3-12 mg/day; maximum 12 mg/day 2

For Schizoaffective Disorder:

• Adults: Initial dose 6 mg/day; recommended range 3-12 mg/day; maximum 12 mg/day 2

Administration:

• Tablets should be swallowed whole, not chewed, divided, or crushed 2
• Take at the same time each day, preferably in the morning

Clinical Efficacy

• Schizophrenia: Efficacy established in three 6-week trials in adults and one 6-week trial in adolescents 2, 5
• Schizoaffective Disorder: Efficacy established in two 6-week trials in adults 2, 3
• Pooled analysis of three 6-week studies showed significant improvement in PANSS total scores, PANSS subscale factors, and Personal and Social Performance scale scores at all doses compared to placebo 5
• According to the latest treatment guidelines, paliperidone may be considered as a second-line treatment for patients whose first-line treatment was a D2 partial agonist (like aripiprazole) 1

Place in Treatment Algorithm

According to current guidelines 1, 6:

1. First-line treatment: Antipsychotic monotherapy for 4-6 weeks at therapeutic dose
2. If inadequate response: Switch to a different antipsychotic with a different pharmacodynamic profile
   • For patients whose first-line treatment was a D2 partial agonist, paliperidone may be considered as a second-line option 1
3. If still inadequate response after second antipsychotic trial: Consider clozapine

Common Side Effects

• Metabolic effects: Weight gain, hyperglycemia, dyslipidemia 6
• Endocrine effects: Hyperprolactinemia (more common than with other atypical antipsychotics) 4, 7
• Neurological effects: Extrapyramidal symptoms, akathisia, risk of tardive dyskinesia 7
• Cardiovascular effects: QT prolongation, orthostatic hypotension 2
• Other common effects: Headache, dizziness, somnolence, insomnia, nausea 3

Special Populations and Considerations

• Elderly patients with dementia-related psychosis: Increased mortality risk (boxed warning) 2
• Renal impairment: Dosage adjustment required in mild renal impairment (CrCL 50-80 mL/min) 8
• Hepatic impairment: No dose adjustment needed for mild to moderate impairment; insufficient data for severe impairment 2
• Pregnancy: Limited data available; use only if benefits outweigh potential risks

Long-Acting Injectable Formulation

• Available as paliperidone palmitate for monthly or 3-monthly administration
• Useful for patients with adherence issues 7
• Initiation regimen for monthly injection: 150 mg eq. on Day 1 and 100 mg eq. on Day 8, both in deltoid muscle 8
• Maintenance doses range from 25-150 mg eq. monthly 8

Monitoring Recommendations

• Regular assessment of metabolic parameters (weight, blood glucose, lipids)
• Monitoring for extrapyramidal symptoms and tardive dyskinesia
• Prolactin levels if clinically indicated (sexual dysfunction, menstrual irregularities)
• ECG monitoring in patients with risk factors for QT prolongation
• Blood pressure monitoring, particularly when initiating treatment

Common Pitfalls to Avoid

• Inadequate trial duration: Ensure at least 4 weeks at therapeutic dose before determining efficacy 1, 6
• Overlooking hyperprolactinemia: Monitor for symptoms, especially in women 7
• Neglecting metabolic monitoring: Regular assessment of weight, glucose, and lipids is essential
• Improper administration: Tablets must be swallowed whole to maintain extended-release properties 2
• Premature polypharmacy: Antipsychotic monotherapy should be optimized before considering combination therapy 1

Paliperidone represents an important treatment option for schizophrenia and schizoaffective disorder, with the convenience of once-daily dosing and availability in both oral and long-acting injectable formulations to help address adherence challenges that are common in these disorders.