Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study

Abstract

This 13-week, double-blind study evaluated the efficacy and safety of the atypical antipsychotic paliperidone palmitate (recently approved in the United States) versus placebo administered as monthly gluteal injections (after two initial doses given 1 week apart) in acutely symptomatic patients with schizophrenia. Patients (N=388) were randomly assigned (1 : 1 : 1 : 1) to paliperidone palmitate 50, 100, or 150 mg eq. or placebo. As the 150 mg eq. dose was administered to fewer patients (n=30) than planned, meaningful and definitive conclusions cannot be drawn from the results of this group. The change from baseline in Positive and Negative Syndrome Scale total score at endpoint showed improvement in both paliperidone palmitate 50 and 100 mg eq. groups but was significant only in the 100 mg eq. group (P=0.019). The paliperidone palmitate 50 (P=0.004) and 100 mg eq. (P<0.001) groups showed significant improvement in the Personal and Social Performance score from baseline to endpoint versus placebo. Common adverse events (in >or=2% of patients in any group) more frequent with paliperidone palmitate 50 or 100 mg eq. than placebo (>or=5% difference) were headache, vomiting, extremity pain, and injection site pain. Treatment with paliperidone palmitate (100 mg eq.) was efficacious and all doses tested were tolerable.

A Controlled, Evidence-Based Trial of Paliperidone Palmitate, A Long-Acting Injectable Antipsychotic, in Schizophrenia

“…These results are generally consistent with those from other recent studies of paliperidone palmitate for both the acute and maintenance treatment of patients with schizophrenia (Gopal et al, 2010;Hough et al, 2008Hough et al, , 2009Kramer et al, 2010), as well as for the oral formulation, paliperidone (Davidson et al, 2007;Kane et al, 2007;Kramer et al, 2007;Luthringer et al, 2007;Marder et al, 2007). Although in this study, paliperidone palmitate was administered gluteally, it may be administered in the deltoid muscle as well (Hough et al, 2009).…”

Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent‐onset versus more chronic schizophrenia and a history of criminal justice system involvement

“…Similarly, discontinuation of oral APs for safety or tolerability as a first treatment failure event appeared to be similar for both groups (Table 3). Overall, the AE profile of PP was consistent with that reported previously; the most notable events were well‐established risks for injection site pain, akathisia, weight gain and elevated prolactin levels 37, 38, 39. Because individual oral APs included as potential comparators in this study could be deselected and because the documented reasons for deselection were usually related to a history of AEs, relative rates for these events were likely underrepresented in this study.…”

Onset and persistence of efficacy by symptom domain with long-acting injectable paliperidone palmitate in patients with schizophrenia

“…It appears that methodological factors may in part explain differences in placebo response [64,65]. However, placebo responses of a similar magnitude and pattern to those observed in the trials examined here have been demonstrated in similarly designed PP studies in comparable, ethnically diverse patient populations [66,67]. This lends support to the generalizability of the placebo effect observed in this study and to the conclusion drawn regarding the efficacy of PP relative to placebo.…”