Intramuscular long-acting paliperidone palmitate in acute patients with schizophrenia unsuccessfully treated with oral antipsychotics

Abstract

In this prospective multicentre, open-label, 6-month study (Paliperidone Palmitate Flexible Dosing in Schizophrenia [PALMFlexS]), tolerability, safety and treatment response with paliperidone palmitate (PP) were explored in patients with acute symptoms of schizophrenia following switching from previously unsuccessful treatment with oral antipsychotics. This pragmatic study was conducted in a large, more representative sample of the general schizophrenia population compared to randomized controlled pivotal trials, to specifically mimic real-world clinical situations. After initiation on Day 1 and Day 8, patients received PP once monthly at flexible doses (50-150mgeq.) intramuscularly. The primary efficacy outcome was defined as the percentage of patients achieving ≥30% improvement in PANSS total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events (TEAEs). Overall, 212 patients received PP at least once after switching from oral antipsychotics, primarily due to lack of efficacy (45.8%). Significant improvements from BL in mean (SD) PANSS total score were observed from Day 8 onwards (BL to LOCF EP: -31.0 [29.0]; p<0.0001). At endpoint, two-thirds (66.7%) and 43.5% of patients achieved a ≥30% and ≥50% improvement in mean PANSS total score, respectively. PP was associated with significant improvements across secondary measures of symptom severity, subjective well-being, medication satisfaction, illness-related disorders of activity and participation, and patient functioning (p<0.0001; BL to LOCF EP). PP was generally well tolerated, with significant reductions in ESRS total score (p<0.0001) and mainly mild-to-moderate TEAEs. TEAEs reported in ≥5% of patients were injection-site pain (13.7%), insomnia (10.8%), psychotic disorder (10.4%), headache and anxiety (both 6.1%). The PALMFlexS study findings provide valuable pragmatic clinical data on PP treatment in patients with acute schizophrenia previously unsuccessfully treated with oral antipsychotics.

Paliperidone Long-Acting Plasma Level Monitoring and a New Method of Evaluation of Clinical Stability

“…Several factors may contribute to poor adherence, including clinical symptoms as disorganization, cognitive impairments, poor insight, but also dosing frequency, adverse events, and complexity of the treatment regimen. This is the reason why long-acting injectable (LAI) formulations of antipsychotic medications are a good solution to provide sustained therapeutic plasma concentrations for several weeks, reducing the risk of non-adherence, minimizing relapse rates, and providing long-term clinical benefits [3][4][5][6].…”

Switching from oral atypical antipsychotic monotherapy to paliperidone palmitate once-monthly in non-acute patients with schizophrenia: A prospective, open-label, interventional study

“…The Paliperidone Palmitate Flexible Dosing in Schizophrenia (PALMFlexS) study was a prospective, 6-month, pragmatic, interventional study conducted in a large, more representative sample of patients with schizophrenia than those recruited in the pivotal RCTs (Hargarter et al 2015; Schreiner et al 2015b; Schreiner et al 2014a). The study was designed specifically to reflect more closely real-world clinical situations in which the transition to another antipsychotic is performed in previously unsuccessfully treated patients.…”

Real-world adherence and economic outcomes associated with paliperidone palmitate versus oral atypical antipsychotics in schizophrenia patients with substance-related disorders using Medicaid benefits

“…A more recent prospective clinical trial conducted in a more representative sample of patients (i.e., including patients with substance-related disorders) demonstrated symptom improvement associated with PP1M [17]. However, there remains a need to better understand the impact of PP1M specifically within the population of patients with schizophrenia and comorbid substance-related disorders.…”