title: A prospective flexible-dose study of paliperidone palmitate in nonacute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents.
abstract: OBJECTIVE
  The goal of this study was to explore the tolerability, safety, and treatment response of flexible doses of once-monthly paliperidone palmitate (PP) in the subset of nonacute but symptomatic adult patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents in the PALMFlexS (Paliperidone Palmitate Flexible Dosing in Schizophrenia) study.
  
  
  METHODS
  This was an interventional, single-arm, international, multicenter, unblinded, 6-month study performed in patients with schizophrenia. Patients were categorized according to reasons for switching. In patients switching because of lack of efficacy or for other reasons, primary efficacy outcomes were the proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to last-observation-carried-forward end point) and maintained efficacy (defined as noninferiority in the change in PANSS total score at end point versus baseline [Schuirmann's test]), respectively.
  
  
  RESULTS
  A total of 593 patients (intention-to-treat population) were enrolled: 63.1% were male; their mean (SD) age was 38.4 (11.8) years; and 78.6% had paranoid schizophrenia. The main reasons for transition to PP were patient's wish (n = 259 [43.7%]), lack of efficacy (n = 144 [24.3%]), lack of compliance (n = 138 [23.3%]), and lack of tolerability (n = 52 [8.8%]) with the previous oral antipsychotic medication. The recommended PP initiation regimen (150 milligram equivalents [mg eq] day 1 and 100 mg eq day 8) was administered in 93.9% of patients. Mean PANSS total score decreased from 71.5 (14.6) at baseline to 59.7 (18.1) at end point (mean change, -11.7 [15.9]; 95% CI, -13.0 to -10.5; P < 0.0001). Sixty-four percent of patients showed an improvement of ≥20% in PANSS total score, and the percentage of patients rated mildly ill or less in Clinical Global Impression-Severity increased from 31.8% to 63.2%. Mean personal and social performance total score (SD) increased (ie, improved) significantly for all patients from baseline to end point (58.1 [13.4] to 66.1 [15.7]; P < 0.0001).
  
  
  CONCLUSIONS
  The PALMFlexS study is a pragmatic interventional study compared with randomized controlled trials, conducted in a large, more representative sample of patients with schizophrenia, and designed specifically to mimic real-world clinical situations. The findings support the results from randomized controlled studies. They also demonstrate that a clinically relevant treatment response is possible in patients who are considered to be clinically stable by their physician, supporting the use of flexibly dosed PP in such patients. Clinical trials.gov number: NCT01281527.
authors.affiliation: Medical Affairs, Janssen Cilag EMEA, Neuss, Germany. Electronic address: aschrein@its.jnj.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schreiner
authors.affiliation: Biometrics and Reporting, Janssen Cilag Benelux, Tilburg, the Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Bergmans
authors.affiliation: Medical Affairs, Janssen Cilag EMEA, Issy-les-Moulineaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cherubin
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, 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 Affairs, Janssen Cilag EMEA, Neuss, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Hargarter
mesh_terms: D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate / Q000008:administration & dosage* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D000068882:Paliperidone Palmitate
keywords: long-acting antipsychotic; nonacute; paliperidone palmitate; schizophrenia