Time to onset and time to resolution of extrapyramidal symptoms in patients with exacerbated schizophrenia treated with 3-monthly vs once-monthly paliperidone palmitate

Abstract

ObjectiveThe aim of this study was to evaluate the safety of 3-monthly paliperidone palmitate (PP3M) vs once-monthly paliperidone palmitate (PP1M) treatment with regard to extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) in patients with schizophrenia, previously stabilized on PP1M treatment.Patients and methodsData on overall incidence, time to onset (TTO), and time to resolution (TTR) of EPS-related TEAEs (overall, subclasses such as dyskinesia, dystonia, hyperkinesia, parkinsonism, and tremor) from a randomized double-blind (DB) non-inferiority study were compared between PP3M and PP1M. Subgroup analysis was performed by age (18–25, 26–50, and 50+ years) and final open-label (OL) dose (50/75, 100, and 150 mg eq.).ResultsOverall incidence of spontaneously reported EPS-related TEAEs decreased from 12.6% (PP1M) in OL phase to 8.3% (PP3M) and 7.4% (PP1M) in the DB phase; overall median TTO and TTR values were comparable between both groups. Among patients with reported EPS-related TEAEs, the median TTO for all EPS-related TEAEs was 17 days (PP1M) in OL phase and 115 days (PP3M) and 98.5 days (PP1M) in DB phase; median TTR was 36.5 days (PP1M) in OL phase and 91 days (PP3M) and 85.5 days (PP1M) in DB phase. No clear dose- or age-related differences in TTO and TTR of EPS-related TEAEs were noted.ConclusionDespite differences in apparent half-life and pharmacokinetic profiles (peak plasma exposure of PP3M formulation is 70% higher than that of PP1M formulation), both PP3M and PP1M formulations exhibited comparable incidence of EPS-related TEAEs, TTO, and TTR in patients with schizophrenia.

Tolerability profile of paliperidone palmitate formulations: A pharmacovigilance analysis of the EUDRAVigilance database

“…Significant differences but in a diminutive sense were observed for ADR cases with a complete recovery and with reactions not resolved at the time of the last follow-up between ICSRs PP-related and in the reference group. This data correlates well with the type of observed ADRs in PP-related ICSRs as several of the most frequently observed ADRs such as those relative to “Psychiatric disorders” and “Nervous system disorders” are generally characterized by long resolution periods (e.g., literature sources report a median of 91 days for extrapyramidal symptoms) ( 42 , 43 ).…”

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“…A pesar de la menor incidencia de síntomas extrapiramidales asociada con el uso generalizado de antipsicóticos atípicos, siguen siendo un problema clínicamente significativo, por lo que minimizar estos eventos es fundamental desde la perspectiva del médico, el paciente y la familia 23,25 .…”