Amisulpride doses and plasma levels in different age groups of patients with schizophrenia or schizoaffective disorder

Abstract

Because of a unique pharmacodynamic profile, amisulpride seems appropriate for treatment of elderly patients with schizophrenia. In a large-scale naturalistic therapeutic drug monitoring study, daily amisulpride dose, trough and dose-corrected amisulpride plasma levels, co-medication, clinical effectiveness (CGI) and side effects (UKU) were compared between age groups in 395 patients with schizophrenia or schizoaffective disorder (46% women; mean age 39.1 +/- 14.2 years, range 18-83 years) under amisulpride therapy. Mean amisulpride doses (574 +/- 269 mg/day), plasma levels (304 +/- 274 ng/mL), dose-corrected amisulpride plasma levels (C/D ratios, 0.52 +/- 0.41 ng/mL:mg), clinical response (at least moderate improvement, 71.6%), and side effects (any side effect, 32.2%; extrapyramidal symptoms, 14.9%) were comparable between age groups (P > 0.25). At higher age, significantly more benzodiazepines (P = 0.04), non-benzodiazepine hypnotics (P = 0.004) and non-psychotropic medications (P < 0.0001) were prescribed. The naturalistic study showed higher C/D ratios in women (P = 0.019) and a slight increase of C/D ratios with age (P = 0.026), but no substantial age-dependent effects on amisulpride doses or plasma levels. In patients above 60 years, clinical response was associated with lower amisulpride plasma levels (P = 0.016) at comparable doses. Neither the age-dependent decrease of amisulpride clearance nor the significantly higher prevalence of co-morbidity and co-medication seem to be the reasons for definite clinical concerns against amisulpride treatment of elderly if contraindications are seriously taken.

A systematic review and combined meta‐analysis of concentration of oral amisulpride

“…Several studies indicated that there was a weak correlation between dose and amisulpride concentration. The correlation r was in the range of 0.46–0.89 . The subgroup analyses suggested that the pooled plasma/serum concentration of females was higher than that in males ( P = .002, I 2 = 67.6%) in 7 studies .…”

“…Following a full‐text review of the remaining 228 studies, 214 studies were excluded; thus, 14 studies (12 in English and 2 in Chinese) were included in the analyses. Included articles comprised 8 TDM reports, 2 multiple fixed‐dose studies, 2 single photon emission computed tomography and 2 positron emission tomography studies . All included studies came from Germany, France, Belgium, UK, Norway, Czech Republic and China, which were published during 1998–2019.…”

“…A study conducted in Germany with 99 patients suggested that compared with males, females have higher plasma concentrations with similar doses, while no significant difference between sexes was observed in other studies . With respect to age, a study by Wang et al found that elderly people aged >65 years have higher dose‐corrected serum levels in China, while in a study by Muller et al, no substantial age‐dependent effects on amisulpride doses or plasma levels were observed . In other studies, higher amisulpride plasma levels were measured in those receiving comedication with clozapine and lithium …”

“…In Bowskill's study, daily dose explained only 42% of the variation in amisulpride plasma concentration after log10 transformation of dose . A study conducted in Germany with 99 patients suggested that compared with males, females have higher plasma concentrations with similar doses, while no significant difference between sexes was observed in other studies . With respect to age, a study by Wang et al found that elderly people aged >65 years have higher dose‐corrected serum levels in China, while in a study by Muller et al, no substantial age‐dependent effects on amisulpride doses or plasma levels were observed .…”

“…With respect to age, a study by Wang et al found that elderly people aged >65 years have higher dose‐corrected serum levels in China, while in a study by Muller et al, no substantial age‐dependent effects on amisulpride doses or plasma levels were observed . In other studies, higher amisulpride plasma levels were measured in those receiving comedication with clozapine and lithium …”