Abstract
ObjectiveAntipsychotic drug sensitivity in very late-onset schizophrenia-like psychosis (VLOSLP) is well documented, but poorly understood. This study aimed to investigate blood drug concentration, D2/3 receptor occupancy and outcome in VLOSLP during open amisulpride prescribing, and compare this with Alzheimer's disease (AD).
MethodsBlood drug concentration, prolactin, symptoms and extrapyramidal side-effects (EPS) were serially assessed during dose titration. [F-18]fallypride imaging was used to quantify D2/3 receptor occupancy. Average steady-state amisulpride concentration (Caverage, ng/ml) was estimated by incorporating pharmacokinetic (PK) data into an existing population PK model (25AD participants, 20 healthy older people).
ResultsEight patients (target 20) were recruited (six women; 76+-6years; six treatment compliant; five serially sampled; three with paired imaging data). Mean+-SD symptom reduction was 7412% (50-100mg/day; 92.5+-39.4ng/ml). Mild EPS emerged at 96ng/ml (in AD, severe EPS, 50mg/day, 60ng/ml). In three participants, imaged during optimal treatment (50mg/day; 41-70ng/ml), caudate occupancy was 44-59% (58-74% in AD across a comparable Caverage).
ConclusionsDespite the small sample size, our findings are highly relevant as they suggest that, as in AD, 50mg/day amisulpride is associated with >40% occupancy and clinically relevant responses in VLOSLP. It was not possible to fully characterise concentration-occupancy relationships in VLOSLP, and it is thus unclear whether the greater susceptibility of those with AD to emergent EPS was accounted for by increased central drug access. Further investigation of age- and diagnosis-specific threshold sensitivities is warranted, to guide amisulpride prescribing in older people, and therapeutic drug monitoring studies offer a potentially informative future approach. Copyright (c) 2017 John Wiley & Sons, Ltd.