PMID- 21600386
OWN - NLM
STAT- MEDLINE
DCOM- 20110916
LR  - 20171116
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 33
IP  - 3
DP  - 2011 Mar
TI  - Iloperidone for the management of adults with schizophrenia.
PG  - 330-45
LID - 10.1016/j.clinthera.2011.03.006 [doi]
AB  - BACKGROUND: Iloperidone is a second-generation antipsychotic drug approved in May 
      2009 by the US Food and Drug Administration (FDA) for the acute treatment of 
      schizophrenia in adults. It is a piperidinyl-benzisoxazole derivative with mixed 
      serotonin (5HT2A) and D2 dopamine antagonist properties. OBJECTIVE: The purpose 
      of this article was to review the pharmacology, pharmacokinetics, efficacy, 
      safety, and role in treatment for iloperidone in schizophrenia. METHODS: 
      Scientific and clinical data were collected through searches of PubMed, 
      ClinicalTrials.gov, International Pharmaceutical Abstracts, and the FDA, using 
      the search term iloperidone, and limited to English-language articles. Reference 
      lists were reviewed for additional publications. Dates included the beginning of 
      the database through 2010. No limits were placed on study design. RESULTS: In a 
      4-week Phase III trial, iloperidone 12 mg twice daily lowered the Positive and 
      Negative Syndrome Scale (PANSS) total scores to a significantly greater extent 
      than did placebo (-12 vs -7.1; P < 0.01). The ziprasidone active control also 
      separated from placebo (-12.3 vs -7.1; P < 0.05). A pooled analysis of 3 Phase 
      III trials compared iloperidone in divided doses to placebo. The primary outcome 
      was reduction in PANSS scores. Study 1 included iloperidone 4, 8, or 12 mg/d, 
      haloperidol as an active control, and placebo. The PANSS reduction in the 12 mg/d 
      group was significantly greater at end point versus baseline when compared with 
      placebo (-9.9 vs -4.6; P = 0.047). Study 2 included iloperidone 4 to 8 mg/d or 10 
      to 16 mg/d, risperidone 4 to 8 mg/d, or placebo. The primary efficacy measure was 
      change from baseline to end point in the Brief Psychiatric Rating Scale (BPRS). 
      Improvement from baseline on all iloperidone doses was significantly greater than 
      with placebo (4-8 mg/d group: -6.2, P = 0.012; 10-16 mg/d group: -7.2, P = 0.001; 
      placebo, -2.5). Study 3 included iloperidone 12 to 16 mg/d, risperidone 6 to 8 
      mg/d, and placebo. The results on the primary efficacy variable, reduction in the 
      BPRS score, was not significant for the 12 to 16 mg/d group versus placebo (-7.1 
      vs -5.0; P = 0.09), but was significant for the 20 to 24 mg/d iloperidone group 
      (-8.6 vs -5.0; P = 0.01) and for the risperidone group (-11.5 vs 5.0; P < 0.001). 
      A 52-week maintenance trial included iloperidone versus haloperidol as an active 
      control. The primary efficacy variable was time to relapse. Comparison of mean 
      time to relapse of the 2 arms showed no significant difference. The most common 
      adverse events (AEs) associated with iloperidone were dizziness (5.1%-23.2%), dry 
      mouth (5.2%-10.4%), somnolence (4%-13%), and dyspepsia (4.8%-7.8%). AEs appeared 
      dose related. Prescribing information recommends a starting dosage of 1 mg twice 
      daily and then titrated over 7 days to reach a target dosage of 12 to 24 mg/d. 
      The titration is necessary to reduce the risk of orthostatic hypotension-related 
      dizziness. CONCLUSIONS: Data support that when titrated slowly to a therapeutic 
      dosage, iloperidone is generally well tolerated, has a favorable safety profile, 
      and is an effective treatment option in patients with schizophrenia. Its place in 
      therapy and performance in a typical patient population remain to be established. 
      Slow initial titration and twice-daily dosing are potential disadvantages.
CI  - Copyright (c) 2011 Elsevier HS Journals, Inc. All rights reserved.
FAU - Crabtree, Brian L
AU  - Crabtree BL
AD  - Department of Pharmacy Practice, University of Mississippi School of Pharmacy, 
      Jackson, 39216, USA. crabtree@msh.state.ms.us
FAU - Montgomery, John
AU  - Montgomery J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Isoxazoles)
RN  - 0 (Piperidines)
RN  - VPO7KJ050N (iloperidone)
SB  - IM
MH  - Adult
MH  - Antipsychotic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Clinical Trials as Topic
MH  - Humans
MH  - Isoxazoles/administration & dosage/adverse effects/*therapeutic use
MH  - Piperidines/administration & dosage/adverse effects/*therapeutic use
MH  - Schizophrenia/*drug therapy
MH  - Treatment Outcome
EDAT- 2011/05/24 06:00
MHDA- 2011/09/17 06:00
CRDT- 2011/05/24 06:00
PHST- 2011/03/21 00:00 [accepted]
PHST- 2011/05/24 06:00 [entrez]
PHST- 2011/05/24 06:00 [pubmed]
PHST- 2011/09/17 06:00 [medline]
AID - S0149-2918(11)00146-9 [pii]
AID - 10.1016/j.clinthera.2011.03.006 [doi]
PST - ppublish
SO  - Clin Ther. 2011 Mar;33(3):330-45. doi: 10.1016/j.clinthera.2011.03.006.