Evaluation of Treatment Failure in a Randomized, Open-Label Study of Paliperidone Palmitate Versus Oral Antipsychotics for Recent-Onset Schizophrenia or Schizophreniform Disorder

Background: Despite the availability of effective treatments, outcomes for patients with schizophrenia remain poor. Nonadherence is common early in the disease course, a time when the greatest deterioration occurs.

Methods: DREaM (NCT02431702), a randomized, open-label study, compared paliperidone palmitate (PP) versus oral antipsychotics (OAPs) for time to first treatment failure (TtFTF) in recent-onset schizophrenia. It included 3 phases: Part I, 2-month oral run-in; Part II, 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (PP/PP; OAP re-randomized: OAP/OAP or OAP/PP). PP/PP and OAP/OAP comprised the 18-month extended disease progression (EDP) phase.

Results: During Part II, 29.5% of participants in the PP group and 24.8% in the OAP group experienced TF; no significant difference in TtFTF between groups was observed (P=0.377). During the EDP phase, 28.6% participants in the PP/PP group and 44.4% in the OAP/OAP group experienced treatment failure (TF; NNT=6). This difference in TtFTF was not statistically significant (P=0.080). During Part III, 14.3% of participants in the PP/PP group, 15.8% in the OAP/PP group, and 28.6% in the OAP/OAP group experienced TF. This difference in TtFTF was not statistically significant (P=0.067).

Conclusions: Although differences in TtFTF were not statistically significant, numerical differences were observed in Part III and EDP favoring PP. A large persistent study effect evident in Part I may have influenced outcomes. In this context, directional effects observed at the end of the study suggest that, if introduced early in the disease course, PP treatment may improve long-term outcomes in schizophrenia.