title: Efficacy and safety of paliperidone extended release in adolescents with schizophrenia: a randomized, double-blind study.
abstract: OBJECTIVE
  To evaluate the efficacy, safety, and tolerability of paliperidone extended release (ER) relative to aripiprazole in adolescent schizophrenia.
  
  
  METHODS
  In this multicenter, double-blind, phase 3 study (screening [≤3 weeks], with an acute treatment period [8 weeks] and a maintenance period [18 weeks]), adolescents (12-17 years old) with schizophrenia (DSM-IV diagnosis; Positive and Negative Symptom Score [PANSS] total score 60-120) were randomized (1:1) to once-daily paliperidone ER (6 mg per day [days 1-7], flexibly dosed 3, 6, or 9 mg per day from week 2 to end of study [EOS]), or to aripiprazole (2 mg per day [days 1 and 2], 5 mg per day [days 3 and 4], 10 mg per day [days 5-7], flexibly dosed 5, 10, or 15 mg per day [week 2 to EOS]).
  
  
  RESULTS
  Overall, 76% of enrolled patients (174/228) completed the study (paliperidone ER, 75% [85/113]; aripiprazole, 77% [89/115]). There was no significant difference in change in PANSS total scores from baseline to day 56 (primary endpoint) (paliperidone ER versus aripiprazole, -19.3 [13.80] versus -19.8 [14.56], p = .935); responders, 67.9% versus 76.3%, p = .119) and day 182 (-25.6 [16.88] versus -26.8 [18.82], p = .877; responders, 76.8% versus 81.6%, p = .444). All secondary endpoints (maintenance of clinical stability, change in PANSS-negative symptoms, Clinical Global Impression-Severity, and Personal and Social Performance scores) were similar in both treatment groups. The most common (>10% patients) treatment-emergent adverse events for paliperidone ER were akathisia, headache, somnolence, tremor, and weight gain, and for aripiprazole were worsening of schizophrenia and somnolence. Extrapyramidal symptoms including dystonia and hyperkinesia occurred in >2% in paliperidone ER-treated versus aripiprazole-treated patients.
  
  
  CONCLUSIONS
  Paliperidone ER did not demonstrate superior efficacy to aripiprazole in treating adolescent schizophrenia. Both drugs showed clinically meaningful improvements in symptom and functional measurements and were generally tolerable. Clinical Trial Registration Information-An Efficacy and Safety Study of Extended-Release (ER) Paliperidone in Adolescent Participants With Schizophrenia; http://clinicaltrials.gov; NCT01009047.
authors.affiliation: Janssen Research and Development, LLC, Titusville, NJ. Electronic address: asavitz@its.jnj.com.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Savitz
authors.affiliation: Janssen Research and Development, LLC, Titusville, NJ.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Lane
authors.affiliation: Janssen Research and Development, LLC, Titusville, NJ.
authors.forename: Isaac
authors.initials: I
authors.lastname: Nuamah
authors.affiliation: Janssen Research and Development, LLC, Titusville, NJ.
authors.forename: Srihari
authors.initials: S
authors.lastname: Gopal
authors.affiliation: Janssen Research and Development, LLC, Titusville, NJ.
authors.forename: David
authors.initials: D
authors.lastname: Hough
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000068180:Aripiprazole / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003692:Delayed-Action Preparations; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006261:Headache; D006801:Humans; D007194:India; D008297:Male; D000068882:Paliperidone Palmitate / Q000008:administration & dosage* / Q000009:adverse effects; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States; D015430:Weight Gain
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D000068180:Aripiprazole; D000068882:Paliperidone Palmitate
keywords: aripiprazole; flexibly dosed; paliperidone extended-release; schizophrenia