title: Paliperidone palmitate versus risperidone long-acting injection in markedly-to-severely ill schizophrenia subjects: onset of efficacy with recommended initiation regimens.
abstract: OBJECTIVE
  To examine onset of efficacy of two long-acting injectable atypical antipsychotics in markedly-to-severely ill schizophrenia subjects.
  
  
  METHODS
  This subgroup analysis included 292 subjects with baseline Clinical Global Impressions-Severity scores of markedly ill or worse from a 13-week, randomized, double-dummy noninferiority study (NCT00589914). Subjects received either: 1) paliperidone palmitate (PP; 234 mg day 1 and 156 mg day 8 [corresponding to 150 and 100 milligram equivalents of paliperidone, respectively], both administered in deltoid muscle, followed by once-monthly flexible dosing in deltoid or gluteal muscle) and risperidone long-acting injection (RLAI)-matched placebo injections; or, 2) RLAI (25 mg, days 8 and 22; followed by biweekly flexible dosing) and PP-matched placebo injections. RLAI subjects received oral risperidone days 1-28; PP subjects received oral placebo. Because of RLAI's release profile, data through day 22 correspond to oral risperidone. Assessments included Positive and Negative Syndrome Scale (PANSS) and adverse event (AE) reports. Paired t-tests assessed within-group changes.
  
  
  RESULTS
  LS mean (SE) PANSS total scores improved significantly (both p<.001) with PP and oral risperidone by day 4 (-5.0 [0.6] and -3.4 [0.6], respectively) through day 22; and with PP and RLAI through end point (-21.5 [1.9] and -18.6 [1.9], respectively). The between-group difference was significant only at day 4 (p=.006). Proportion of subjects with a .30% reduction in PANSS total score was not significantly different between the two groups at day 4 and was significantly greater with paliperidone palmitate than oral risperidone at days 15 and 22 (26.1% versus 12.7%, p=.013; 41.6% versus 32.0%, p=.048, respectively). Most common AEs (.5% in either treatment group): headache (PP 6.3% and RLAI 14.0%), insomnia (10.6% and 10.7%), somnolence (7.8% and 1.3%), akathisia (7.0% and 5.3%), schizophrenia (8.5% and 5.3%), agitation (5.6% and 2.0%), and injection site pain (5.6% and 1.3%).
  
  
  CONCLUSIONS
  Using the recommended dosing regimens for PP and RLAI, both PP and oral risperidone (used during RLAI initiation) improved symptoms of schizophrenia in markedly-to-severely ill subjects at days 4-22.
authors: Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
authors: Dong-Jing
authors: DJ
authors: Fu
authors: Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
authors: Cynthia A
authors: CA
authors: Bossie
authors: Janssen Pharmaceuticals, Titusville, NJ, USA.
authors: Jennifer
authors: J
authors: Kern Sliwa
authors: Johnson & Johnson Consumer Products US, Horsham, PA, USA.
authors: Yi-Wen
authors: YW
authors: Ma
authors: Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
authors: Larry
authors: L
authors: Alphs
mesh_terms: D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D000068882:Paliperidone Palmitate; D010168:Palmitates / Q000008:administration & dosage / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D010168:Palmitates; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: Comparative; Efficacy; Initiation Regimens; Markedly Ill; Onset; Paliperidone Palmitate; Risperidone Long-Acting; Schizophrenia