Poster #S250 PRESCRIPTION PATTERNS PRIOR TO CLOZAPINE INITIATION IN FIRST-EPISODE PSYCHOSIS

Abstract

Background: Many antipsychotic drugs, including perphenazine, are routinely administered in a divided dosage regimen because of their relatively short plasma half-lives. Whether this is actually necessary has never been extensively investigated. The objective of this study was to evaluate the impact of once vs. twice daily dosing of perphenazine on clinical outcomes in patients with schizophrenia. Methods: Data from phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) were used. Patients with schizophrenia 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. These two groups were compared regarding the following outcomes: Effectiveness – discontinuation rate and time to discontinuation (primary outcomes): Efficacy – Positive and Negative Syndrome Scale, Clinical Global Impression – Severity scale, Calgary Depression Scale for Schizophrenia, and Drug Attitude Inventory; Safety/Tolerability – Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale, Simpson-Angus Scale, body weight, treatment emergent adverse events, and concomitant psychotropic medications; Medication Adherence – Pill count and clinician rating scale. 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 average dose of perphenazine as a covariate. Discussion: The present findings indicate that despite a pharmacokinetic rationale supporting dosing of perphenazine at least twice daily, once daily dosing produces similar clinical outcomes. These findings also suggest it may be necessary to revisit the longstanding axiom that antipsychotic dosing be established based on peripheral pharmacokinetics.