CoChat
Sign Up
Cited by 12Schizophrenia research and treatmentPharmaceutical studies and practicesPharmacogenetics and Drug Metabolism

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

Open access
O’Neill, James R., Taylor, David M., Horowitz, Mark A.·2023·Therapeutic Advances in Psychopharmacology
DOI 10.1177/20451253231198463PMC PMC10501077
Open this paper in CoChat — free account

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1177/20451253231198463

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Even slow tapering of depot preparations by extending the dosing interval and lowering to the smallest available dose may present too fast a reduction in MOR for some patients to tolerate.

    “However, as previously demonstrated for antipsychotic depots,68,69 even slow tapering of depot preparations by extending the dosing interval and lowering to the smallest available dose may present too fast a reduction in MOR for some patients to tolerate (e.g. those who require 1% reductions per week).”

    From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [68]

    The Results (Summary of dose reduction regimens; Summary of pharmacokinetic modelling, pages not provided) model a ‘slow’ aripiprazole depot taper by extending dosing intervals and reducing to 300 mg, while noting that a tolerable rate of D2-occupancy reduction is unknown. The Limitations section says patients vary and symptoms should guide reductions. The paper does not establish that this slow regimen is too fast for patients needing 1% reductions per week, nor does its aripiprazole model establish that for depot preparations generally. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Abrupt cessation of even the smallest dose of depot may entail too rapid a reduction in MOR for some patients and so will require a switch to oral medication to complete the taper.

    “It is likely that abrupt cessation of even the smallest dose of depot may entail too rapid a reduction in MOR for some patients and so will require a switch to oral medication to complete the taper. 68”

    From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [68]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
O’Neill, J. R., Taylor, D. M., & Horowitz, M. A.
Affiliations
  • South West Yorkshire Partnership NHS Foundation Trust (GB)
  • Maudsley Hospital (GB)
  • University College London (GB)
Corresponding author
O’Neill, James R.
ORCID
Venue
Therapeutic Advances in Psychopharmacology
Publisher
SAGE Publications
Published
2023-01
Volume
13
Pages
20451253231198463-20451253231198463
ISSN
  • 2045-1253 (ISSN-L)
  • 2045-1261
DOI
10.1177/20451253231198463
PMC
PMC10501077
OpenAlex
W4386709768
Cited by
12
References
49
Citations by year
2026: 3 · 2025: 5 · 2024: 4
FWCI
0.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Therapeutic Advances in Psychopharmacology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
long-acting injectable antipsychotics, aripiprazole, gradual dose reduction, dopamine D2 receptor occupancy, abrupt discontinuation, withdrawal effects, relapse prevention, pharmacokinetic modeling, in silico modeling

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review