title: Impact of once- versus twice-daily perphenazine dosing on clinical outcomes: an analysis of the CATIE data.
abstract: OBJECTIVE
  The objective of this study was to evaluate the impact of once- versus twice-daily dosing of perphenazine, which has a plasma half-life of 8-12 hours, on clinical outcomes in patients with schizophrenia.
  
  
  METHODS
  Data from phase 1 of the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) conducted between January 2001 and December 2004 were used in this post hoc analysis. Patients with schizophrenia (DSM-IV) randomly allocated to treatment with perphenazine were also randomly assigned to once-daily (N = 133) or twice-daily (N = 124) dosing and followed over 18 months. Discontinuation rate and time to discontinuation were used as primary outcomes to compare the 2 groups. The following clinical outcomes were analyzed as secondary measures: efficacy-Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity scale, Calgary Depression Scale for Schizophrenia, and Drug Attitude Inventory and safety/tolerability-Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale, Simpson-Angus Scale, and body weight. Data on treatment-emergent adverse events, concomitant psychotropic medications, and medication adherence (pill count and clinician rating scale) were also analyzed for each group.
  
  
  RESULTS
  No significant differences were found in any outcome measures between the once-daily and twice-daily dosing groups, which remained the same when using the mean dose of perphenazine as a covariate.
  
  
  CONCLUSIONS
  Perphenazine is routinely administered in a divided dosage regimen because of its relatively short plasma half-life. However, the present findings challenge such a strategy, suggesting that once-daily represents a viable treatment option. Results are discussed in the context of more recent evidence that challenges the need for high and continuous dopamine D2 receptor blockade to sustain antipsychotic response.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00014001.
authors.affiliation: Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario, M5T 1R8, Canada hirotak@dk9.so-net.ne.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Gagan
authors.initials: G
authors.lastname: Fervaha
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
authors.forename: David
authors.initials: D
authors.lastname: Grönte
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017321:Clinical Trials, Phase I as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010546:Perphenazine / Q000008:administration & dosage* / Q000009:adverse effects; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010546:Perphenazine