Comparison of long-acting and oral antipsychotic treatment effects in patients with schizophrenia, comorbid substance abuse, and a history of recent incarceration: An exploratory analysis of the PRIDE study.

INTRODUCTION: Comorbid substance abuse is known to blunt response to treatment for underlying psychiatric disorders, but it has not been investigated in schizophrenia when comparing the effects of long-acting injectable antipsychotics with those of oral antipsychotics. METHODS: This exploratory analysis compared once-monthly paliperidone palmitate (PP1M) with daily oral antipsychotics on time to treatment failure in patients with schizophrenia and a history of incarceration. Subjects were stratified into substance abuse (reported substance or alcohol misuse in the past 30days on the baseline Addiction Severity Index-Lite Version and/or met criteria for a current MINI diagnosis of a substance abuse disorder) and nonabuse cohorts. RESULTS: In the substance abuse cohort, treatment failure was observed in 56.2% (73/130) and 64.2% (86/134) of subjects in the PP1M and oral antipsychotic groups, respectively. For the nonabuse cohort, treatment failure was observed in 36.5% (35/96) and 53.6% (45/84) of subjects in the PP1M and oral antipsychotic groups, respectively. Median (95% confidence interval [CI]) time to first treatment failure was 291 (179-428) days and 186 (94-296) days in the PP1M and oral antipsychotic groups, respectively. Median (95% CI) time to first treatment failure was >450 and 284 (147 to >450) days in the respective treatment groups. CONCLUSION: Greater treatment effects were evident with PP1M compared with oral antipsychotics in both cohorts. The observed beneficial effect of PP1M was attenuated in the substance-abuse cohort, further reinforcing both the need for and value of continued research to optimize patient care in these complex patient populations.

A pragmatic analysis comparing once-monthly paliperidone palmitate versus daily oral antipsychotic treatment in patients with schizophrenia.

BACKGROUND: Persons with schizophrenia often come in contact with the criminal justice system (CJS). This analysis of subjects with schizophrenia and a history of contact with the CJS estimated and compared mean cumulative function (MCF) of treatment failure events when treated with paliperidone palmitate (PP) or oral antipsychotics (OAs). All events identified during the full study period of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) trial were evaluated. METHODS: Subjects were randomly assigned to flexibly dosed, monthly, injectable PP (78-234 mg) or daily OA in a 15-month prospective, open-label, multicenter US study (May 5, 2010-December 9, 2013). Subjects could continue participation after a treatment failure event. Multiple treatment failures in individual subjects were analyzed as recurrent events. Analyses estimated MCF of treatment failure events and MCF of institutionalizations (arrests, incarcerations, or psychiatric hospitalizations) during the 15-month study period. RESULTS: The ITT population included 226 (PP) and 218 (OA) subjects, of whom 41.2% and 40.4%, respectively, completed 15 months of follow-up. The MCF of treatment failures and institutionalizations differed significantly in favor of PP compared with OA (P=0.007 and P=0.005, respectively). Overall, TEAEs were reported by 86.3% of subjects in the PP group and 81.7% in the OA group. CONCLUSIONS: This pragmatic analysis suggests that, compared with OA, PP is not only more effective in delaying median time to treatment failure, but it also reduces the number of treatment failures and institutionalizations per person-year follow-up. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov identifier: NCT01157351.