ArticleClinical pharmacology : advances and applications2012
Management of antipsychotic treatment discontinuation and interruptions using model-based simulations.
Article in Clinical pharmacology : advances and applications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Pooled it
- Prospective dose selection and acceleration of paliperidone palmitate 3-month formulation development using a pharmacometric bridging strategy.British journal of clinical pharmacology · 2016Trial
- Exploring Patient, Caregiver, and Prescriber Preferences for an Injectable Antipsychotic Administered Every 2 Months for the Maintenance Treatment of Schizophrenia: A Multicenter Qualitative Interview Study Conducted in Europe.Patient preference and adherence · 2025Article
- Precision Nanomedicine: Lapatinib-Loaded Chitosan-Gold Nanoparticles Targeting LINC01615 for Lung Cancer Therapy.The AAPS journal · 2024Article
- External Validation of the Population Pharmacokinetic Models of Amisulpride and Remedial Strategies for Delayed or Missed Doses.Drug design, development and therapy · 2024Article
- Factors associated with medication interruption among outpatients with severe mental illness exposed to COVID-19.Frontiers in public health · 2023Article
- Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview.CNS drugs · 2021Review
- How to Handle Delayed or Missed Doses: A Population Pharmacokinetic Perspective.European journal of drug metabolism and pharmacokinetics · 2020Review
- The Effects of Paliperidone Palmitate 1 Month on the Employment Status and Social Functioning of Patients with Schizophrenia.Innovations in clinical neuroscience · 2020Article
- Regularity of self-reported daily dosage of mood stabilizers and antipsychotics in patients with bipolar disorder.International journal of bipolar disorders · 2018Article
- Treatment continuation of four long-acting antipsychotic medications in the Netherlands and Belgium: A retrospective database study.PloS one · 2017Article
- Model-based clinical drug development in the past, present and future: a commentary.British journal of clinical pharmacology · 2015Review
- Efficacy, safety, and impact on hospitalizations of paliperidone palmitate in recent-onset schizophrenia.Neuropsychiatric disease and treatment · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMedication nonadherence is a well described and prevalent clinical occurrence in schizophrenia. These pharmacokinetic model-based simulations analyze predicted antipsychotic plasma concentrations in nonadherence and treatment interruption scenarios and with treatment reinitiation.
methodsStarting from steady state, pharmacokinetic model-based simulations of active moiety plasma concentrations of oral, immediate-release risperidone 3 mg/day, risperidone long-acting injection 37.5 mg/14 days, oral paliperidone extended-release 6 mg/day, and paliperidone palmitate 117 mg (75 mg equivalents)/28 days were assessed under three treatment discontinuation/interruption scenarios, ie, complete discontinuation, one week of interruption, and four weeks of interruption. In the treatment interruption scenarios, pharmacokinetic simulations were performed using medication-specific reinitiation strategies.
resultsFollowing complete treatment discontinuation, plasma concentrations persisted longest with paliperidone palmitate, followed by risperidone long-acting injection, while oral formulations exhibited the most rapid decrease. One week of oral paliperidone or risperidone interruption resulted in near complete elimination from the systemic circulation within that timeframe, reflecting the rapid elimination rate of the active moiety. After 1 and 4 weeks of interruption, minimum plasma concentrations were higher with paliperidone palmitate than risperidone long-acting injection over the simulated period. Four weeks of treatment interruption followed by reinitiation resulted in plasma levels returning to predicted therapeutic levels within 1 week.
conclusionDue to the long half-life of paliperidone palmitate (25-49 days), putative therapeutic plasma concentrations persisted longest in simulated cases of complete discontinuation or treatment interruption. These simulations may help clinicians better conceptualize the impact of antipsychotic nonadherence on plasma concentrations, and the impact of medication-specific reinitiation strategies after intermittent nonadherence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.