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

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. 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.