Background: Advantages of atypical antipsychotics compared with older conventional agents are a topic of controversy. This exploratory analysis from the Paliperidone palmitate Research in Demonstrating Effectiveness (PRIDE) study compared once-monthly paliperidone palmitate (PP) with conventional oral antipsychotics (OAs).
Methods: 15-month prospective, randomized, open-label, event-monitoring board-blinded study, randomly assigned 444 subjects with schizophrenia to PP or daily OAs (from a preselected group of 7 commonly prescribed medications). Primary endpoint was time to first treatment failure: 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. This exploratory analysis reported randomization-based individual comparisons of PP versus the conventional OA haloperidol (n=89 and n=15, respectively), and perphenazine (n=132 and n=20, respectively).
Results: Compared with PP, risk for first treatment failure was 95% higher with haloperidol (HR: 1.95 [95% CI, 0.97-3.91]); the comparison to perphenazine yielded an HR of 1.01 (0.50-2.04). Mean (SD) daily dose of prescribed haloperidol and perphenazine: 8.2 (5.3) and 16.5 (8.8) mg, respectively. Mean (SD) monthly PP dose for haloperidol and perphenazine comparisons: 173.8 (34.5) and 177.1 (33.7) mg, respectively. Subjects reporting extrapyramidal symptom-related adverse events (AEs): 53.3% haloperidol, 40% perphenazine, and 23.9% PP. Subjects reporting prolactin-related AEs: 13.3%, 0%, and 23.5%, respectively. Subjects with ≥7% weight increase: 20.0%, 5.0%, and 32.4%, respectively.
Conclusions: Exploratory analyses suggest differential treatment effects and side effect profiles of once-monthly PP compared with conventional oral antipsychotics.