A Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of 3 Doses of Paliperidone Palmitate in Adults With Acutely Exacerbated Schizophrenia

Abstract

This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate (approved in the USA, August 2009) for adult patients with acutely exacerbated schizophrenia. The patients (N = 652) were randomly assigned (1:1:1:1) to paliperidone palmitate at 25, 100, or 150 mg eq. or placebo in this 13-week double-blind study. The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or gluteal [corrected] on day 8 and then once monthly (days 36 and 64). No oral supplementation was used. Target plasma levels were achieved by day 8 in all paliperidone palmitate groups. The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly (P < or = 0.034) in all the paliperidone palmitate dose-groups versus placebo. Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle. Common treatment-emergent adverse events (> or =2% of patients in any of the treatment groups) that occurred more frequently in the total paliperidone palmitate group versus the placebo group (with > or =1% difference) were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%). The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range (25, 100, or 150 mg eq.) in adult patients with acutely exacerbated schizophrenia.

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.…”

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

“…Although LAIs are typically advocated for relapse prevention in patients with chronic schizophrenia, 6 data from placebo-controlled, randomized controlled trials (RCTs) show that these agents also reduce symptoms when administered as first-line therapy in acutely ill patients. [7][8][9] Placebo-controlled RCTs have also demonstrated reduction in relapses with long-acting formulations of second-generation antipsychotics (SGAs) administered at intervals of biweekly to once every 3 months, including paliperidone palmitate (39-156 mg every 4 weeks or 273-819 mg every 3 months), olanzapine pamoate (150 or 300 mg every 2 weeks or 405 mg every 4 weeks), aripiprazole monohydrate (400 mg every 4 weeks), and aripiprazole lauroxil (441, 662, or 882 every 4 weeks or 881 mg every 6 weeks). 10,11 RCTs that have compared LAI antipsychotics with placebo in patients with schizophrenia are summarized in Table 1.…”

“…10,11 RCTs that have compared LAI antipsychotics with placebo in patients with schizophrenia are summarized in Table 1. [7][8][9][11][12][13][14][15][16][17] Notably, newer studies of SGA LAIs were sometimes discontinued prematurely on the basis of interim analyses demonstrating efficacy. 11,17 This early discontinuation may underestimate the true magnitude of improvement that would have been observed had all patients been followed for a longer period of time (eg, 1 year), as was more typical with older studies of first-generation antipsychotics (FGAs).…”

“…6 Looking at the effect of medication gaps reveals that even missing 1 to 10 days of medication leads to nearly twice the odds of hospitalization compared with a person who has no medication gaps. 7 The risk of relapse increases with more time spent off an antipsychotic. 8 There is also an increase in suicide attempt rate when atypical antipsychotic therapy is interrupted.…”

Paliperidone Palmitate Once-Monthly Reduces Risk of Relapse of Psychotic, Depressive, and Manic Symptoms and Maintains Functioning in a Double-Blind, Randomized Study of Schizoaffective Disorder

“…22 Long-acting injectable therapies, such as once-monthly paliperidone palmitate (paliperidone monthly), provide consistent therapeutic plasma concentrations over several weeks, eliminating the need for daily oral medication and facilitating monitoring of treatment adherence. 23,24 Building on efficacy data of oral paliperidone in acute management of schizoaffective disorder, 5,6 this relapse-prevention study was designed to compare paliperidone monthly given as monotherapy or with adjunctive antidepressants or mood stabilizers to placebo in patients with schizoaffective disorder.…”