PMID- 21481243
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20220318
IS  - 1744-859X (Electronic)
IS  - 1744-859X (Linking)
VI  - 10
IP  - 1
DP  - 2011 Apr 11
TI  - Onset of efficacy with acute long-acting injectable paliperidone palmitate 
      treatment in markedly to severely ill patients with schizophrenia: post hoc 
      analysis of a randomized, double-blind clinical trial.
PG  - 12
LID - 10.1186/1744-859X-10-12 [doi]
AB  - BACKGROUND: This post hoc analysis (trial registration: ClinicalTrials.gov 
      NCT00590577) assessed onset of efficacy and tolerability of acute treatment with 
      once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic 
      initiated by day 1 and day 8 injections, in a markedly to severely ill 
      schizophrenia population. METHODS: Subjects entering the 13-week, double-blind 
      trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of 
      paliperidone, respectively]) or placebo. This subgroup analysis included those 
      with a baseline Clinical Global Impressions-Severity (CGI-S) score indicating 
      marked to severe illness. PP subjects received a 234-mg day 1 injection 
      (deltoid), followed by their assigned dose on day 8 and monthly thereafter 
      (deltoid or gluteal). Thus, data for PP groups were pooled for days 4 and 8. 
      Measures included Positive and Negative Syndrome Scale (PANSS), CGI-S, Personal 
      and Social Performance (PSP), and adverse events (AEs). Analysis of covariance 
      (ANCOVA) and last-observation-carried-forward (LOCF) methodologies, without 
      multiplicity adjustments, were used to assess changes in continuous measures. 
      Onset of efficacy was defined as the first time point a treatment group showed 
      significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92) versus 
      placebo, which was maintained through end point. RESULTS: A total of 312 subjects 
      met inclusion criterion for this subgroup analysis. After the day 1 injection, 
      mean PANSS total scores improved significantly with PP (all received 234 mg) 
      versus placebo at day 4 (P = 0.012) and day 8 (P = 0.007). After the day 8 
      injection, a significant PANSS improvement persisted at all subsequent time 
      points in the 234-mg group versus placebo (P < 0.05). PANSS improvements were 
      greater from day 36 through end point in the 156-mg group (P < 0.05) and only at 
      end point in the 39-mg group (P < 0.05). CGI-S and PSP scores improved 
      significantly in the 234-mg and 156-mg PP groups versus placebo at end point (P < 
      0.05 for both, respectively); improvement in the 39-mg group was not significant. 
      The most common AEs for PP-treated subjects (>/=10%, any treatment group) were 
      headache, insomnia, schizophrenia exacerbation, injection site pain, and 
      agitation. CONCLUSIONS: In this markedly to severely ill population, acute 
      treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 
      4. After subsequent injections, observed improvements are suggestive of a 
      dose-dependent effect. No unexpected tolerability findings were noted.
FAU - Alphs, Larry
AU  - Alphs L
AD  - Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ, USA. 
      lalphs@its.jnj.com.
FAU - Bossie, Cynthia A
AU  - Bossie CA
FAU - Sliwa, Jennifer K
AU  - Sliwa JK
FAU - Ma, Yi-Wen
AU  - Ma YW
FAU - Turner, Norris
AU  - Turner N
LA  - eng
SI  - ClinicalTrials.gov/NCT00590577
PT  - Journal Article
DEP - 20110411
PL  - England
TA  - Ann Gen Psychiatry
JT  - Annals of general psychiatry
JID - 101236515
PMC - PMC3082227
EDAT- 2011/04/13 06:00
MHDA- 2011/04/13 06:01
PMCR- 2011/04/11
CRDT- 2011/04/13 06:00
PHST- 2010/12/21 00:00 [received]
PHST- 2011/04/11 00:00 [accepted]
PHST- 2011/04/13 06:00 [entrez]
PHST- 2011/04/13 06:00 [pubmed]
PHST- 2011/04/13 06:01 [medline]
PHST- 2011/04/11 00:00 [pmc-release]
AID - 1744-859X-10-12 [pii]
AID - 10.1186/1744-859X-10-12 [doi]
PST - epublish
SO  - Ann Gen Psychiatry. 2011 Apr 11;10(1):12. doi: 10.1186/1744-859X-10-12.