UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

A Population Approach to Guide Amisulpride Dose Adjustments in Older Patients With Alzheimer's Disease

Reeves, S; Bertrand, J; McLachlan, E; D'Antonio, F; Brownings, S; Nair, A; Greaves, S; ... Howard, R; + view all (2017) A Population Approach to Guide Amisulpride Dose Adjustments in Older Patients With Alzheimer's Disease. Journal of Clinical Psychiatry , 78 (7) e844-e851. 10.4088/JCP.16m11216.

[img] Text
Manuscript_J16-M11216_R1_101216.pdf - Accepted version
Access restricted to UCL open access staff

Download (465kB)

Abstract

Objective: We have previously reported high dopamine D2/3 receptor occupancies at low amisulpride concentrations in older people with Alzheimer’s disease (AD), during off-label treatment of AD-related psychosis. This post hoc analysis explored pharmacokinetic (concentration) and pharmacodynamic (prolactin, D2/3 occupancy) contributions to symptom reduction and extrapyramidal side effects (EPS) to inform AD-specific dose adjustments. Methods: Population pharmacokinetic-pharmacodynamic models were developed by combining pharmacokinetic data from a phase 1 study in 20 healthy older people with pharmacokinetic prolactin, [18F]fallypride D2/3 receptor imaging, and clinical outcome data from 28 older patients prescribed open amisulpride (25–75 mg/d) to treat AD-related psychosis. Model predictions were used to simulate dose-response and dose-EPS. Results: Symptom reduction (delusions) was associated with amisulpride concentration (P = 1.3e-05) and D2/3 occupancy (P < .01, caudate, putamen, thalamus). Model predictions suggested that across concentrations of 40–100 ng/mL, and occupancies of 40% to 70% in the caudate and thalamus and 30% to 60% in the putamen, there was a 50% to 90% probability of response and < 30% probability of EPS. Simulations, based on concentration-delusions and concentration-EPS model outputs, showed that 50 mg/d of amisulpride was the appropriate dose to achieve this target range in those aged > 75 years; increasing the dose to 75 mg/d increased the risk of EPS, particularly in those aged > 85 years of low body weight. Conclusions: These findings argue strongly for the consideration of age- and weight-based dose adjustments in older patients with AD-related psychosis and indicate that 50 mg/d of amisulpride may be both the minimal clinically effective dose and, in those aged > 75 years, the maximally tolerated dose.

Type: Article
Title: A Population Approach to Guide Amisulpride Dose Adjustments in Older Patients With Alzheimer's Disease
DOI: 10.4088/JCP.16m11216
Publisher version: http://doi.org/10.4088/JCP.16m11216
Language: English
Keywords: Pharmacokinetic-pharmacodynamic, amisulpride, D2/3 occupancy, adverse effects, antipsychotic, Alzheimer’s
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/1561234
Downloads since deposit
2Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item