Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine‑resistant treatment‑refractory schizophrenia:a 12‑week randomized,double‑blind,placebo‑controlled trial

Background:Although clozapine is an effective option for treatment-resistant schizophrenia(TRS),there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine.The main purpose of this randomized,double-blind,placebocontrolled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia(CTRS)patients.Methods:A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride(amisulpride group)or clozapine plus placebo(placebo group).Positive and Negative Syndrome Scale(PANSS),Scale for the Assessment of Negative Symptoms(SANS),Clinical Global Impression(CGI)scale scores,Repeatable Battery for the Assessment of Neuropsychological Status(RBANS),Treatment Emergent Symptom Scale(TESS),laboratory measurements,and electrocardiograms(ECG)were performed at baseline,week 6,and week 12.Results:Compared with the placebo group,amisulpride group had a lower PANSS total score,positive subscore,and general psychopathology subscore at week 6 and week 12(PBonferroni<0.01).Furthermore,compared with the placebo group,the amisulpride group showed an improved RBANS language score at week 12(PBonferroni<0.001).Amisulpride group had a higher treatment response rate(P=0.04),lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group(PBonferroni<0.05).There were no differences between the groups in body mass index(BMI),corrected QT(QTc)intervals,and laboratory measurements.This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients.

Repetitive transcranial magnetic stimulation combined with olanzapine and amisulpride for treatment-refractory schizophrenia

BACKGROUND Treatment-refractory schizophrenia(TRS),accounting for approximately 30%of all schizophrenia cases,has poor treatment response and prognosis despite treatment with antipsychotic drugs.AIM To analyze the therapeutic effectiveness of repetitive transcranial magnetic stimulation(rTMS)combined with olanzapine(OLZ)and amisulpride(AMI)for TRS and its influence on the patient’s cognitive function.METHODS This study enrolled 114 TRS patients who received treatment at the First Affiliated Hospital of Zhengzhou University between July 2019 and July 2022.In addition to the basic OLZ+AMI therapy,54 cases of the control group(Con group)received modified electroconvulsive therapy,while 60 cases of the research group(Res group)received rTMS.Data on therapeutic effectiveness,safety(incidence of drowsiness,headache,nausea,vomiting,or memory impairment),Positive and Negative Symptom Scale,Montreal Cognitive Assessment Scale,and Schizophrenia Quality of Life Scale were collected from both cohorts for comparative analyses.RESULTS The Res group elicited a higher overall response rate and better safety profile when compared with the Con group.Additionally,a significant reduction was observed in the post-treatment Positive and Negative Symptom Scale and Schizophrenia Quality of Life Scale scores of the Res group,presenting lower scores than those of the Con group.Furthermore,a significant increase in the Montreal Cognitive Assessment Scale score was reported in the Res group,with higher scores than those of the Con group.CONCLUSION The treatment of TRS with rTMS and OLZ+AMI is effective and safe.Moreover,it can alleviate the patients’mental symptoms,improve their cognitive function and quality of life,and has a high clinical application value.

Modeling and simulation for individualized therapy of amisulpride in Chinese patients with schizophrenia:focus on inter interindi⁃vidual variability,therapeutic reference range and laboratory alert level

OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.