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Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study

Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles in silico to long-acting aripiprazole to generate regimens f...

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Autores principales: O’Neill, James R., Taylor, David M., Horowitz, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501077/
https://www.ncbi.nlm.nih.gov/pubmed/37719449
http://dx.doi.org/10.1177/20451253231198463
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author O’Neill, James R.
Taylor, David M.
Horowitz, Mark A.
author_facet O’Neill, James R.
Taylor, David M.
Horowitz, Mark A.
author_sort O’Neill, James R.
collection PubMed
description Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles in silico to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted in silico modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D(2) occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D(2) occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D(2) occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D(2) occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication – 5, 2.5 and 1.25 mg for the three regimens, respectively – is required for ALAI to complete full cessation to prevent too rapid a reduction in D(2) occupancy. Oral medication should probably be maintained at a consistent dose for 3–6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication.
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spelling pubmed-105010772023-09-15 Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study O’Neill, James R. Taylor, David M. Horowitz, Mark A. Ther Adv Psychopharmacol Long-Acting Antipsychotic Treatments Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles in silico to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted in silico modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D(2) occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D(2) occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D(2) occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D(2) occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication – 5, 2.5 and 1.25 mg for the three regimens, respectively – is required for ALAI to complete full cessation to prevent too rapid a reduction in D(2) occupancy. Oral medication should probably be maintained at a consistent dose for 3–6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication. SAGE Publications 2023-09-13 /pmc/articles/PMC10501077/ /pubmed/37719449 http://dx.doi.org/10.1177/20451253231198463 Text en © The Author(s), 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Long-Acting Antipsychotic Treatments
O’Neill, James R.
Taylor, David M.
Horowitz, Mark A.
Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study
title Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study
title_full Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study
title_fullStr Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study
title_full_unstemmed Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study
title_short Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study
title_sort implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study
topic Long-Acting Antipsychotic Treatments
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501077/
https://www.ncbi.nlm.nih.gov/pubmed/37719449
http://dx.doi.org/10.1177/20451253231198463
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