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

Abstract

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.

Discontinuation rates during long‐term, second‐generation antipsychotic long‐acting injection treatment: A systematic review

“…A comparison between patients treated with PP1M and patients treated with FGA also showed small differences in the rate of premature discontinuation. In the PP1M group, the most frequent cause of dropout was loss to follow‐up …”

“…The most significant finding emerging from the reviewed studies on PP1M was that the drug showed lower (or, at best, similar) dropout rates in all but one head‐to‐head comparison with several comparators, such as RIS‐LAI, FGA‐LAI, and both FGA and SGA in oral formulation …”

“…38 The most significant finding emerging from the reviewed studies on PP1M was that the drug showed lower (or, at best, similar) dropout rates in all but one head-to-head comparison with several comparators, such as RIS-LAI, FGA-LAI, and both FGA and SGA in oral formulation. 47,[49][50][51]53,55 The only study reporting the advantage of PP1M on oral antipsychotics showed several limitations, the main being a suboptimal statistical power due to the small sample size and the inclusion in the study cohort of both new and old PP1M users. 54 The main causes of drug discontinuation before the planned study end were adverse events 45,46,61,62,65 and ineffectiveness.…”

“…In the PP1M group, the most frequent cause of dropout was loss to follow-up. 49,50 A long-term study compared the effectiveness of PP1M versus haloperidol decanoate. 51 No differences in the discontinuation rate were found between the groups.…”

Long-acting injectable aripiprazole in pregnant women with schizophrenia: a case-series report

“…Furthermore, from a pharmacokinetic point of view, after a single dosage of a LAI formulation, relapse prevention derived for antipsychotic plasma levels enough to block up to 60% D2 receptors remains active for several weeks (up to 24 weeks if we use paliperidone LAI monthly). 41,42 All patients were closely monitored by multidisciplinary clinical staff to detect the presence of risk signs or complications (psychiatry, obstetricgynecology, endocrinology, and rheumatology).…”