title: 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.
authors.affiliation: Medical & Scientific Affairs, Janssen Cilag EMEA, Neuss, Germany. Electronic address: lhargart@its.jnj.com.
authors.forename: Ludger
authors.initials: L
authors.lastname: Hargarter
authors.affiliation: Medical Affairs, Janssen Cilag EMEA, Issy-les-Moulineaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cherubin
authors.affiliation: Biometrics and Reporting, Janssen Cilag Benelux, Tilburg, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Bergmans
authors.affiliation: Global Clinical Operations EMEA MAO, Janssen Cilag, Barcarena, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Keim
authors.affiliation: Department of Psychiatry and Narcology, Riga Stradins University, Riga, Latvia.
authors.forename: Elmars
authors.initials: E
authors.lastname: Rancans
authors.affiliation: Dicle University Medical Faculty, Diyarbakir, Turkey.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bez
authors.affiliation: Barcelona Clinic Schizophrenia Unit (BCSU), Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Parellada
authors.affiliation: Clinica Psichiatrica Università di Cagliari, Cagliari, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Carpiniello
authors.affiliation: Centre Hospitalier Régional Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vidailhet
authors.affiliation: Medical & Scientific Affairs, Janssen Cilag EMEA, Neuss, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schreiner
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D000068882:Paliperidone Palmitate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D019233:Retreatment; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: Acute; Efficacy; Long-acting; Paliperidone palmitate; Schizophrenia; Switching