Therapeutic D2/3 receptor occupancies and response with low amisulpride blood concentrations in very late-onset schizophrenia-like psychosis (VLOSLP)

Suzanne Reeves, Kate Eggleston, Elizabeth Cort, Emma McLachlan, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, Joel Dunn, Paul Marsden, Robert Kessler, David Taylor (+2 others)
2017 International Journal of Geriatric Psychiatry  
Objective: Antipsychotic 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). Methods: Blood drug concentration, symptoms (suspiciousness, unusual thought content, hallucinations) and extrapyramidal side-effects (EPS), were serially assessed
more » ... ng dose titration. [ 18 F]fallypride imaging was used to estimate D2/3 receptor occupancy. Average steady state drug concentration (Caverage) was estimated by incorporating pharmacokinetic (PK) data into an existing population PK model (25 AD participants, 20 healthy older people). Results: Eight patients (original target 20) were recruited (6 women; 76  6 years), 6 of whom complied with treatment: blood samples were obtained from 5; and paired imaging data from 3 participants. Mean+-SD reduction in symptoms was 74 ± 12% (Caverage 92.5+-39.4ng/ml). Mild EPS (Simpson Angus Scale, SAS, score of 4), which did not lead to treatment withdrawal, emerged at Caverage 96ng/ml (in AD, severe EPS, SAS score of 15, emerged at 60ng/ml). In 3 participants, imaged at an optimal dose of 50mg/day (Caverage 41-70ng/ml), caudate occupancy was 44-59% (compared to 58-74% in AD). Conclusions: Despite small sample size, our findings are highly relevant and suggest that, similar to AD, 50mg/day amisulpride is associated with clinically relevant responses and occupancies >40% in VLOSLP. Although the two groups overlap in terms of minimum clinically effective dose, the AD group were more susceptible to emergent EPS. It is unclear, due to small sample size, whether these differences are accounted for by a steeper concentrationoccupancy curve in AD. Therapeutic drug monitoring studies of amisulpride offer a potentially feasible approach to future investigation of age and disease-specific threshold sensitivities for EPS. Alongside this, research should focus on understanding and addressing barriers to service engagement in VLOSLP
doi:10.1002/gps.4758 pmid:28643852 fatcat:eocm6hlpabgxvckydh27spen3y