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Impact of once- versus twice-daily perphenazine dosing on clinical outcomes: an analysis of the CATIE data.

AbstractOBJECTIVE:
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.
METHOD:
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.
TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT00014001.
AuthorsHiroyoshi Takeuchi, Gagan Fervaha, Hiroyuki Uchida, Takefumi Suzuki, Robert R Bies, David Grönte, Gary Remington
JournalThe Journal of clinical psychiatry (J Clin Psychiatry) Vol. 75 Issue 5 Pg. 506-11 (May 2014) ISSN: 1555-2101 [Electronic] United States
PMID24569099 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
Copyright© Copyright 2014 Physicians Postgraduate Press, Inc.
Chemical References
  • Antipsychotic Agents
  • Perphenazine
Topics
  • Adult
  • Antipsychotic Agents (administration & dosage, adverse effects)
  • Clinical Trials, Phase I as Topic
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Medication Adherence
  • Middle Aged
  • Perphenazine (administration & dosage, adverse effects)
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic
  • Schizophrenia (drug therapy)
  • Time Factors
  • Treatment Outcome

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