title: A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine.
abstract: OBJECTIVE
  The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER).
  
  
  METHODS
  Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤ 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change.
  
  
  RESULTS
  Of 396 patients, 65.2% were men, mean age was 40.0 ± 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥ 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 ± 5.2 kg at endpoint, and a clinically relevant weight gain of ≥ 7% occurred in 8.0% of patients.
  
  
  CONCLUSIONS
  Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine.
authors.affiliation: KOTLER: Beer Yaakov-Ness Ziona Mental Health Center, Beer Yaakov, Israel; and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel DILBAZ: Üsküdar University Neuropsychiatry Hospital, Istanbul, Turkey PATERAKIS: Hospital Dromokaiteio Therapeftirio, Chaidari, Athens, Greece MILANOVA: Department of Psychiatry, Medical University, Sofia, Bulgaria SMULEVICH: Research Clinical Department of Boundary Conditions and Psychosomatic Disorders, Mental Health Research; and Department of Psychiatry and Psychosomatics, I.M. Sechenov First Moscow Stare Medical University, Moscow, Russia LAHAYE: Medical Affairs EMEA, Janssen-Cilag BV, Tilburg, The Netherlands SCHREINER: Medical and Scientific Affairs EMEA, Janssen-Cilag GmbH, Neuss, Germany.
authors.forename: Moshe
authors.initials: M
authors.lastname: Kotler
authors.forename: Nesrin
authors.initials: N
authors.lastname: Dilbaz
authors.forename: Fernanda
authors.initials: F
authors.lastname: Rosa
authors.forename: Periklis
authors.initials: P
authors.lastname: Paterakis
authors.forename: Vihra
authors.initials: V
authors.lastname: Milanova
authors.forename: Anatoly B
authors.initials: AB
authors.lastname: Smulevich
authors.forename: Marjolein
authors.initials: M
authors.lastname: Lahaye
authors.forename: Andreas
authors.initials: A
authors.lastname: Schreiner
mesh_terms: D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D000068882:Paliperidone Palmitate / Q000008:administration & dosage* / Q000009:adverse effects; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D001569:Benzodiazepines; D000077152:Olanzapine; D000068882:Paliperidone Palmitate
references.citation: Schizophr Res. 2011 Aug;130(1-3):40-6
references.pmid: 21624824
references.citation: J Clin Psychopharmacol. 2010 Oct;30(5):487-95
references.pmid: 20814330
references.citation: Int Clin Psychopharmacol. 2007 Sep;22(5):299-308
references.pmid: 17690599
references.citation: J Clin Psychiatry. 2006;67 Suppl 5:9-14
references.pmid: 16822091
references.citation: J Psychiatr Pract. 2015 Jul;21(4):267-74
references.pmid: 26164052
references.citation: Curr Med Res Opin. 2006 Oct;22(10):1879-92
references.pmid: 17022845
references.citation: Expert Opin Pharmacother. 2014 Apr;15(5):593-603
references.pmid: 24491033
references.citation: Int J Psychiatry Clin Pract. 2014 Jan;18(1):58-62
references.pmid: 24047427
references.citation: BMC Psychiatry. 2011;11:21
references.pmid: 21299844
references.citation: Int Clin Psychopharmacol. 2008 Nov;23(6):343-56
references.pmid: 18854723
references.citation: Ind Psychiatry J. 2011 Jan;20(1):25-31
references.pmid: 22969177
references.citation: Neuropsychopharmacology. 2010 Jan;35(2):581-90
references.pmid: 19890258
references.citation: Neuropsychiatr Dis Treat. 2012;8:113-8
references.pmid: 22536066
references.citation: Schizophr Res. 2005 Nov 15;79(2-3):231-8
references.pmid: 15982856
references.citation: Psychiatr Serv. 2010 Apr;61(4):405-8
references.pmid: 20360281
references.citation: Neuropsychopharmacology. 2006 Oct;31(10):2318-25
references.pmid: 16823384
references.citation: J Clin Psychiatry. 2008 May;69(5):817-29
references.pmid: 18466043
references.citation: Eur Psychiatry. 2010 Mar;25(2):92-100
references.pmid: 19640686
references.citation: J Clin Psychiatry. 1997 Dec;58(12):538-46
references.pmid: 9448657
references.citation: Biol Psychiatry. 2009 Mar 15;65(6):510-7
references.pmid: 18986646
references.citation: Schizophr Res. 2005 Jul 15;76(2-3):247-65
references.pmid: 15949657
references.citation: J Nerv Ment Dis. 1994 Nov;182(11):631-8
references.pmid: 7964671
references.citation: Expert Opin Drug Deliv. 2009 Mar;6(3):319-31
references.pmid: 19317589
references.citation: Acta Psychiatr Scand. 2000 Apr;101(4):323-9
references.pmid: 10782554
references.citation: J Clin Psychiatry. 2010 May;71(5):587-98
references.pmid: 20492853
references.citation: Int J Clin Pharmacol Ther. 2010 Jun;48(6):383-99
references.pmid: 20497747
references.citation: Clin Ther. 2010 Feb;32(2):275-92
references.pmid: 20206786
references.citation: Int Clin Psychopharmacol. 2012 Sep;27(5):267-74
references.pmid: 22809972
references.citation: Lancet. 2013 Sep 14;382(9896):951-62
references.pmid: 23810019
references.citation: Cochrane Database Syst Rev. 2012;(6):CD008296
references.pmid: 22696377
references.citation: J Clin Psychopharmacol. 2012 Aug;32(4):449-57
references.pmid: 22722501
references.citation: Schizophr Bull. 1987;13(2):261-76
references.pmid: 3616518
references.citation: Schizophr Res. 2008 Jan;98(1-3):318-22
references.pmid: 17949948
references.citation: Int Clin Psychopharmacol. 2008 Jul;23(4):209-15
references.pmid: 18545059
references.citation: CNS Drugs. 2008;22(11):939-62
references.pmid: 18840034