Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia

CNS Spectr. 2016 Dec;21(6):466-477. doi: 10.1017/S1092852916000444. Epub 2016 Sep 15.


Objective: This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).

Methods: PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.

Results: Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.

Conclusions: Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Keywords: Long-acting injectable antipsychotic; PRIDE; oral antipsychotic; paliperidone palmitate; schizophrenia.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / therapeutic use
  • Aripiprazole / therapeutic use
  • Basal Ganglia Diseases / chemically induced
  • Benzodiazepines / therapeutic use
  • Delayed-Action Preparations
  • Female
  • Haloperidol / therapeutic use
  • Humans
  • Hyperprolactinemia / chemically induced
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Olanzapine
  • Paliperidone Palmitate / administration & dosage*
  • Paliperidone Palmitate / therapeutic use
  • Perphenazine / therapeutic use
  • Proportional Hazards Models
  • Quetiapine Fumarate / therapeutic use
  • Risperidone / therapeutic use
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology
  • Treatment Failure
  • Treatment Outcome


  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Benzodiazepines
  • Quetiapine Fumarate
  • Aripiprazole
  • Perphenazine
  • Haloperidol
  • Risperidone
  • Olanzapine
  • Paliperidone Palmitate