Background: Long-acting injectable antipsychotics are typically reserved for patients with schizophrenia who have a long history of illness. Their benefit for patients recently diagnosed has not been well studied. The Paliperidone palmitate Research In Demonstrating Effectiveness (PRIDE) study compared once-monthly paliperidone palmitate (PP) to daily oral antipsychotics (OAs) in patients with schizophrenia early in their illness in an exploratory analysis.
Methods: Prospective, randomized, open-label, event monitoring board-blinded study of subjects randomized to PP or OA (assigned randomly from a prespecified list of 7 OAs) for 15 months. Treatment failure was defined as arrest/incarceration, psychiatric hospitalization, suicide, discontinuation due to inadequate efficacy or safety/tolerability, treatment supplementation due to inadequate efficacy, or increase in psychiatric services to prevent psychiatric hospitalization. Event-free probabilities estimated using Kaplan-Meier method; hazard ratios (HR) estimated using Cox proportional hazards models. Data analyzed by disease duration (≤5 [early-illness] or >5 years [chronic-illness] since diagnosis).
Results: 77 subjects had early-illness (42 PP, 35 OA); 365 had chronic-illness (183 PP, 182 OAs). Treatment failure risk was higher with OAs vs PP in both groups; early-illness: HR [95% CI] 1.73 [0.87-3.45], P=0.116; chronic-illness: 1.37 [1.02-1.85], P=0.038. Most common adverse events in early-illness group: injection-site pain (PP vs OAs; 26% vs 0%), increased weight (14% vs 6%), akathisia (14% vs 9%), insomnia (12% vs 17%), and anxiety (12% vs 6%).
Conclusions: Hazard ratios suggest that PP may have more robust effect reducing risk of treatment failure versus OAs for patients with schizophrenia early in their illness than patients with more chronic illness.