Changes of Mental State and Serum Prolactin Levels in Patients with Schizophrenia and Depression after Receiving the Combination Therapy of Amisulpride and Chloroprothixol Tablets.

OBJECTIVE: To investigate the changes in mental state and serum prolactin levels in patients with schizophrenia and depression after receiving the combination therapy of amisulpride and chloroprothixol tablets. METHODS: A total of 148 schizophrenic patients with depression were randomly divided into control group (N = 73) and study group (N = 75). The control group was treated with clopidothiol, and the study group was treated with amisulpride. Symptom scores, sleep quality, adverse reactions, therapeutic effects, prolactin, and progesterone levels, HAMD, PANSS, and PSP scores were compared between the two groups. RESULTS: The symptom scores of both groups were significantly reduced, but when compared to the control group, the symptom scores of the research group were significantly reduced more significantly (P < 0.05); serum GDNF levels of both groups were significantly increased, while serum NSE, IL-1, and MBP levels were significantly reduced (P < 0.05). However, the research group altered more substantially (P < 0.05) than the control group; the overall PSQI score of the research group was lower (P < 0.05) than the control group; and the incidence of adverse responses in the control and study groups was 12.3 percent and 4.0 percent. The research group had a lower rate of adverse responses (P < 0.05) than the control group, and the effective treatment of the control and research groups was 82.2 percent and 98.7%, respectively. The research group had a lower rate of adverse reactions (P < 0.05) than the control group, while the control and research groups' successful treatment rates were 82.2 percent and 98.7%, respectively. When compared to the control group, the research group had a greater treatment efficiency (P < 0.05); blood prolactin and progesterone levels were considerably lowered in both groups, but the reductions in the research group were more evident (P < 0.05). Both groups had considerably lower HAMD and PANSS scores, and both had significantly higher PSP scores, although the difference in the research group was more evident (P < 0.05). CONCLUSION: For people with schizophrenia and depression, a combination of amisulpride and chloroprothixol pills has a considerable effect. It can help patients with their clinical symptoms and sleep quality while also lowering their serum prolactin levels, which is favorable to their illness recovery. As a result, the combined treatment of amisulpride and chloroprothixol pills deserves to be promoted and used.

Modeling and Simulation for Individualized Therapy of Amisulpride in Chinese Patients with Schizophrenia: Focus on Interindividual Variability, Therapeutic Reference Range and the Laboratory Alert Level.

PURPOSE: To explain the high inter-individual variability (IIV) and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride, a population pharmacokinetic (PPK) model in Chinese patients with schizophrenia was built based on therapeutic drug monitoring (TDM) data to guide individualized therapy. PATIENTS AND METHODS: Plasma concentration data (330 measurements from 121 patients) were analyzed using a nonlinear mixed-effects modeling (NONMEM) approach with first-order conditional estimation with interaction (FOCE I). The concentrations 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 validated using goodness-of-fit, bootstrap and normalized prediction distribution error (NPDE). Recommended 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 concentration 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, respectively. Age significantly affected the clearance of amisulpride and the final model was as follows: CL/F=1.04×(AGE/32)-0.624 (L/h). To avoid exceeding the laboratory alert level (640 ng/mL), the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg/d for patients aged 60 years, 800 mg/d for those aged 40 years and 1200 mg/d for those aged 20 years, respectively. CONCLUSION: 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 individualized therapy for Chinese patients with schizophrenia.

Differential Effectiveness of Atypical Antipsychotics on Hallucinations: A Pragmatic Randomized Controlled Trial.

BACKGROUND: Most studies investigating antipsychotic effectiveness report either total psychopathology or symptom cluster findings. Studies focusing on a separate symptom, such as hallucinations, a hallmark symptom in schizophrenia, are scarce.Therefore, the current study aims to compare the antihallucinatory effectiveness of 3 pharmacologically different antipsychotics: olanzapine, amisulpride, and aripiprazole. METHODS: The present study is part of the Bergen-Stavanger-Innsbruck-Trondheim study, a 12-month prospective, randomized, pragmatic antipsychotic drug trial in active-phase schizophrenia spectrum disorders. The primary outcome of the present study was change of hallucinations as measured by item P3 (hallucinatory behavior) from the Positive and Negative Syndrome Scale in the subgroup with hallucinations at baseline. Primary analyses were intention to treat. RESULTS: A total of 144 participants were included in the study, where 105 (72%) had a score of 3 or more on the Positive and Negative Syndrome Scale P3 item at baseline, indicating the presence of hallucinations (HALL subgroup).In the HALL subgroup, a significantly less reduction of hallucinations was revealed for participants using olanzapine in weeks 12, 26, 39, and 52 when compared with amisulpride and in weeks 26 and 52 when compared with aripiprazole. In subanalyses for participants never exposed to antipsychotic drugs (antipsychotic-naive) and those who had used antipsychotics before entering the study, antihallucinatory differences were revealed only in the latter group. CONCLUSIONS: A differential antihallucinatory effect of the 3 study drugs was present. The inferior effect of olanzapine seems to be driven by the subgroup of participants exposed to antipsychotic treatment before entering the study.

The effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic paraventricular nucleus.

Antipsychotics, including amisulpride (AMI), quetiapine (QUE), aripiprazole (ARI), and olanzapine (OLA), are used to treat mental illnesses associated with psychotic symptoms. The effect of these drugs on c-Fos expression in vasopressinergic (AVP) and oxytocinergic (OXY) neurons was studied in the hypothalamic paraventricular nucleus (PVN) of rats. The presence of c-Fos in AVP and OXY perikarya was investigated in seven PVN cells segregations: the anterior (Ant), dorsal cup (Dc), wing-shaped (Wi), periventricular zone (Pe), circle-shaped core (Co) and shell of core (Sh), and the posterior (pPVN) after an acute treatment with AMI-20 mg/kg, QUE-15 mg/kg, ARI-10 mg/kg, and OLA-5 mg/kg/bw in rats. Ninety min after treatments, the animals were sacrificed by transcardial perfusion with fixative and the PVN area sliced into 35 µm thick coronal sections for immunohistochemistry. The c-Fos was processed by avidin-biotin-peroxidase complex intensified with nickel-enhanced 3,3'-diaminobenzidine tetrahydrochloride. Visualization of AVP- and OXY-synthesizing neurons was achieved by a fluorescent marker Alexa Flour 568. The c-Fos-AVP and c-Fos-OXY colocalizations were evaluated from c-Fos stained sections merged with AVP or OXY ones. AMI, QUE, ARI, and OLA, single administration distinctly increased the c-Fos expression in each of the PVN cells segregations. QUE induced the highest magnitude of activation of AVP and OXY neurons, while OLA and AMI had only moderate effects. Incontestable variabilities detected in c-Fos expression in PVN AVP and OXY neurons extend the knowledge of selected antipsychotics extra-striatal actions and may also be helpful in a presumption of their possible functional impact.

Amisulpride: A Review in Post-Operative Nausea and Vomiting.

Amisulpride intravenous (IV) injection (Barhemsys®; hereafter referred to as IV amisulpride), a selective dopamine receptor antagonist, is approved in the USA as a single IV infusion for the prevention and treatment of post-operative nausea and vomiting (PONV) in adults. Results from placebo-controlled phase III trials showed that IV amisulpride is efficacious both in the prevention of PONV (used either alone or in combination with an antiemetic of a different class) and in the treatment of PONV (irrespective of prior antiemetic prophylaxis status). When administered as a single IV infusion, amisulpride had a tolerability profile that was generally similar to that of placebo, with no significant safety concerns identified. Thus, IV amisulpride is a useful additional option in the prevention and treatment of PONV in adults, particularly for patients who have failed previous antiemetic prophylaxis and for whom effective treatment options may be limited.

Intravenous Amisulpride Does Not Meaningfully Prolong the QTc Interval at Doses Effective for the Management of Postoperative Nausea and Vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant issues in surgical patients, and additional treatment options are needed. Dopaminergic antiemetics have been popular for their efficacy, but their use has been limited by safety concerns, especially the potential for torsade de pointes arising from QT interval prolongation. Intravenous (IV) amisulpride, a dopamine D2 and D3 antagonist shown to be effective at preventing and treating PONV at doses of 5 and 10 mg, respectively, has a dose-dependent effect on QT but at 5 mg is not associated with clinically meaningful prolongation of the heart rate-corrected QT (QTc) interval. This study was designed to evaluate the QT effect of a 10-mg dose of amisulpride, alone and when simultaneously coadministered with ondansetron, an antiemetic of a different class, also known to prolong the QT interval. METHODS: In this randomized, double-blind, placebo-controlled, 3-period, crossover study, healthy male and female volunteers 18-65 years of age received IV, in a random sequence: (1) amisulpride 10 mg given twice, 2 hours apart; (2) amisulpride 10 mg and ondansetron 4 mg, given simultaneously; and (3) placebo. RESULTS: Thirty subjects were enrolled, and 29 completed all 3 treatment periods. The largest mean placebo-corrected change-from-baseline QT interval corrected for heart rate using Fridericia's formula (QTcF) (ΔΔQTcF) after the first and second amisulpride dose was 5.2 milliseconds (90% confidence interval [CI], 3.53-6.96 milliseconds) and 8.0 milliseconds (90% CI, 5.49-10.58 milliseconds), respectively. After coadministration of amisulpride and ondansetron, the largest mean ΔΔQTcF was 7.3 milliseconds (90% CI, 5.48-9.16 milliseconds). The slope of the amisulpride concentration-change-from-baseline QTcF (ΔQTcF) relationship was 0.006 ms/ng/mL (90% CI, 0.0020-0.0098). No QTc outliers (absolute QTcF value >480 milliseconds or increase from baseline >30 milliseconds) were seen in any period. CONCLUSIONS: A 10-mg dose of IV amisulpride, given alone or in combination with ondansetron, does not have a clinically significant effect on the QT interval.

The Opioid Interactions of the Antipsychotic Medications Risperidone and Amisulpride in Mice and Their Potential Use in the Treatment of Other Non-Psychotic Medical Conditions.

Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. The opioid epidemic in the USA has highlighted the need for alternative treatments for pain. Following reports on the opioid interactions of various antipsychotic medications, we speculated that the involvement of the opioid system in some of the antipsychotics' mechanism of action may suggest their potential use in the treatment of pain. Risperidone is a neuroleptic with a potent dopamine D2 and serotonin 5-HT2 receptor-blocking activity as well as a high affinity for adrenergic and histamine H1 receptors. Amisulpride is a neuroleptic which selectively blocks dopamine D2 and D3 receptors. Both had a potent antinociceptive effect on ICR mice tested with a tail flick assay. That effect on both medications was antagonized by naloxone, indicating that at least some of the antinociceptive effects were mediated by an opioid mechanism of action. Further investigation found that ß-Funaltrexamine hydrochloride (ß-FNA), naloxonazine, and nor-Binaltorphimine dihydrochloride (nor-BNI) reversed the antinociceptive effect of both risperidone and amisulpride. Naltrindole at a dose that blocked [D-Pen2,D-Pen5]enkephalin (DPDPE, δ analgesia) blocked notably amisplride effect and only partially reversed that of risperidone. Risperidone induced an antinociceptive effect, implying involvement of µ and κ-opioid and δ-opioid mechanisms. Amisulpride-induced antinociception was mediated through selective involvement of all three opioid receptor subtypes. These findings emphasize the need for clinical trials to assess the possibility of extending the spectrum of medications available for the treatment of pain.

Dopaminergic and opioidergic regulation during anticipation and consumption of social and nonsocial rewards.

The observation of animal orofacial and behavioral reactions has played a fundamental role in research on reward but is seldom assessed in humans. Healthy volunteers (N = 131) received 400 mg of the dopaminergic antagonist amisulpride, 50 mg of the opioidergic antagonist naltrexone, or placebo. Subjective ratings, physical effort, and facial reactions to matched primary social (affective touch) and nonsocial (food) rewards were assessed. Both drugs resulted in lower physical effort and greater negative facial reactions during reward anticipation, especially of food rewards. Only opioidergic manipulation through naltrexone led to a reduction in positive facial reactions to liked rewards during reward consumption. Subjective ratings of wanting and liking were not modulated by either drug. Results suggest that facial reactions during anticipated and experienced pleasure rely on partly different neurochemical systems, and also that the neurochemical bases for food and touch rewards are not identical.

Studies in rats and other species have shown that two chemical messengers in the brain regulate how much an animal desires a reward, and how pleasant receiving the reward is. In this context, chemicals called opioids control both wanting and enjoying a reward, whereas a chemical called dopamine only regulates how much an animal desires it. However, since these results were obtained from research performed on animals, further studies are needed to determine if these chemicals play the same roles in the human brain. Korb et al. show that the same brain chemicals that control reward anticipation and pleasure in rats are also at work in humans. In the experiment, 131 healthy volunteers received either a drug that blocks opioid signaling in the brain, a drug that blocks dopamine signaling, or a placebo, a pill with no effect. Then, participants were given, on several occasions, either sweet milk with chocolate or a gentle caress on the forearm. Participants rated how much they wanted each of the rewards before receiving it, and how much they liked it after experiencing it. To measure their implicit wanting of the reward, participants also pressed a force-measuring device to increase their chances of receiving the reward. Additionally, small electrodes measured the movement of the volunteer's smiling or frowning muscles to detect changes in facial expressions of pleasure. Volunteers taking either drug pressed on the device less hard than the participants taking the placebo, suggesting they did not want the rewards as much, and they frowned more as they anticipated the reward, indicating less anticipatory pleasure. However, only the volunteers taking the opioid-blocking drug smiled less when they received a reward, indicating that these participants did not get as much pleasure as others out of receiving it. These differences were most pronounced when volunteers looked at or received the sweet milk with chocolate. This experiment helps to shed light on the chemicals in the human brain that are involved in reward-seeking behaviors. In the future, the results may be useful for developing better treatments for addictions.

c-Fos and FosB/ΔFosB colocalizations in selected forebrain structures after olanzapine, amisulpride, aripiprazole, and quetiapine single administration in rats preconditioned by two different mild stressors sequences.

OBJECTIVE: Olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) belong to antipsychotics, which administration represents still most reliable way for the treatment of schizophrenic and bipolar disorders. The intention of the present study was to explore whether the acute administration of a particular antipsychotic, indicated by the presence of c-Fos, will: a) stimulate neurons already activated by a long lasting homogeneous or heterogeneous stress preconditioning, indicated by the FosB/ΔFosB (ΔFosB) expression, or b) have a stimulatory effect only on a not activated, so called silent neurons. The pattern of ΔFosB and c-Fos spatial relationship was investigated in three forebrain structures, including the septal ventrolateral nucleus (seVL), the striatal dorsolateral area (stDL), and the shell of the nucleus accumbens (shell). METHODS: The rats were divided into 10 groups and exposed to two types of stressors. Half of them was exposed to a sequence of homogeneous stressor - handling (HDL) and the other half to a heterogeneous stressor (CMS) daily for 20 days. CMS consisted of five types of stressors: crowding, air-puff, wet bedding, predator stress, and forced swimming applied in an unexpected order. On the 21st day of the experiment, the rats were free of the stress exposure and on the 22nd day, both groups of animals receive a single intraperitoneal injection of vehicle (4% DMSO in saline, 0.1 ml/100 g) or OLA (5 mg/kg), AMI (20 mg/kg), ARI (10 mg/kg), and QUE (15 mg/kg). 90 min after the drugs administration the animals were transcardially perfused, brains removed, cut into 30 µm thick coronal sections, and double stained: first with ΔFosB antibody linked with Alexa488 fluorescent dye and second with c-Fos antibody linked to Alexa596 one. Quantitative evaluation of ΔFosB and c-Fos colocalizations was performed on fluorescence photomicrographs transformed into a final picture containing only yellow, green, and red colored circles. RESULTS: The data of this investigation demonstrate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell ones, in both HDL as well as CMS preconditioned rats. The levels of ΔFosB and c-Fos colocalizations varied in the individual forebrain areas studied. From the total 22 areas measured, level of c-Fos colocalization prevailed over ΔFosB in 18 ones. However, neither c-Fos nor ΔFosB reached 100% level of colocalization in any of the forebrain areas investigated. CONCLUSION: The present findings indicate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell, in both HDL and CMS preconditioned rats, whereas the parallel occurrence of free c-Fos as well as c-Fos colocalized with ΔFosB might speak out for a possible involvement of the c-Fos activated by antipsychotics applied in dual, i.e. short- and long-lasting, functions.

Effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic supraoptic nucleus.

OBJECTIVE: The goal of this study was to reveal the impact of four types of atypical antipsychotics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI), with different receptor-affinity profile and dissociation constant, on the activity of hypothalamic supraoptic nucleus (SON) vasopressinergic and oxytocinergic neurons. METHODS: Male Sprague Dawley rats received a single injection of vehicle (VEH) (0.1 ml/100g), AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg/) or ARI (10 mg/kg). Ninety min after treatment, the animals were fixed by transcardial perfusion, the brains removed, and cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black end product. Afterwards, the sections were exposed to vasopressin (AVP) and oxytocin (OXY) antibodies and the reaction product visualized by biotin-labeled fluorescent Alexa Fluor 568 dye. The data were evaluated from c-Fos and AVP or OXY merged sections. RESULTS: The present study shows that all four antipsychotics applied induced c-Fos expression in the SON. With respect to the stimulation efficacy of the individual antipsychotics, estimated based on the quantity of c-Fos-labeled AVP and OXY neurons, could be a preferential action assigned to QUE over moderate effect of ARI and lower effect to OLA and reduced effect of AMI (VEH < AMI < OLA < ARI < QUE). CONCLUSION: The present data for the first time provide an insight into the quantitative pattern of brain activity within the clusters of SON AVP and OXY cells in response to different atypical antipsychotics single treatment.

Comparative cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China.

BACKGROUND: Both amisulpride and olanzapine are leading treatments for schizophrenia in China. This study aimed to investigate the long-term cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China. METHODS: A decision-analytic Markov model was developed to simulate the lifetime clinical and economic outcomes of schizophrenia treatment from the healthcare payer perspective. The long-term costs and QALYs were estimated. Sensitivity analyses were performed to explore the impact of variance of parameters on the results. RESULTS: Treatment with amisulpride provided an effectiveness gain of 16.59 QALYs at an average cost of USD 25,884 whereas olanzapine resulted in 16.38 QALYs at a cost of USD 34,839 over a lifetime horizon. One-way sensitivity analysis suggested that the most sensitive variable was the unit cost of olanzapine. In a probabilistic sensitivity analysis based on a Monte Carlo simulation with a lifetime horizon, the probability of amisulpride being cost-effective was 99.8% at a willingness-to-pay threshold of USD 9,322, the GDP per capita in China 2018. A scenario analysis with updated olanzapine unit cost suggested an ICER of 7,857 USD/QALY. CONCLUSIONS: Amisulpride is likely to be a cost-effective option with increased effectiveness compared with olanzapine in the treatment of schizophrenia patients in China.

A pharmacological profile of intravenous amisulpride for the treatment of postoperative nausea and vomiting.

INTRODUCTION: The issue of postoperative nausea and vomiting (PONV) remains important in surgical practice, contributing to patient distress, slower recovery, and increased use of healthcare resources. Many surgical patients report it to be a worse problem than the pain. New antiemetics of different classes are still needed to help manage PONV effectively, especially the treatment of established PONV after the failure of common prophylactic antiemetics such as 5-HT3-antagonists and corticosteroids. Intravenous amisulpride, a drug with a long history of safe use in oral form as an antipsychotic, has recently been approved in the US (trade name: Barhemsys) as an intravenous antiemetic for the prevention and treatment of PONV. AREAS COVERED: This review article summarizes the published data on the clinical pharmacology, safety, and efficacy of intravenous amisulpride as an antiemetic, supplemented by published data on oral amisulpride, where relevant to the intravenous form. Literature was obtained via the PubMed search terms 'intravenous amisulpride' and 'amisulpride AND safety.' Both primary and secondary pharmacology are covered, along with clinical pharmacokinetics (distribution, metabolism, and excretion). The review of clinical safety and efficacy includes data from four studies in the prevention of PONV, two in the treatment of PONV and two investigating effects on the QT interval of the electrocardiogram in healthy volunteers. EXPERT OPINION: Given the importance of sufficient PONV prevention for patients and the healthcare system, the availability of intravenous amisulpride is helpful, restoring the dopamine-antagonist class as a potential mainstay in both combination prophylaxis and treatment.

A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort).

BACKGROUND: Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. AIMS: We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. METHODS: All subjects included for this genome-wide association study (n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment. RESULTS: Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; ß=1.05; p=3.66 × 10-08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 (p=1.0 × 10-03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. CONCLUSION: Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.

An overview of intravenous amisulpride as a new therapeutic option for the prophylaxis and treatment of postoperative nausea and vomiting.

Introduction: Current therapies of postoperative nausea and vomiting (PONV) are based on a combination of antiemetics from different pharmacological classes. Dopamine receptor antagonists are one of the cornerstones of such multimodal antiemetic approach, with droperidol being the best studied representative of this group. Droperidol's use has significantly declined after the FDA's black-box warning in 2001 due to its QT-prolonging properties. Amisulpride is a promising antiemetic agent which could fill this gap.Areas covered: In this review, the authors discuss the pharmacological profile as well as clinical safety and efficacy of intravenous amisulpride and its relevance in the management of PONV. The article is based on a Medline, ClinicalTrials.gov, and Cochrane Library search for studies on amisulpride conducted so far.Expert opinion: Promising clinical results on Barhemsys®, an intravenous formulation of amisulpride, make it a potential future drug of choice from the dopamine receptor antagonist group, replacing droperidol after its safety concerns. Amisulpride's success on the market will mostly be determined by its cost-effectiveness and it will likely find a brighter use on the US-market, where the black-box warning led to droperidol's withdrawal, while in many European countries, droperidol is still being used as an antiemetic.

Amisulpride: Real-World Evidence of Dose Adaptation and Effect on Prolactin Concentrations and Body Weight Gain by Pharmacokinetic/Pharmacodynamic Analyses.

BACKGROUND: Amisulpride is an antipsychotic used in a wide range of doses. One of the major adverse events of amisulpride is hyperprolactinemia, and the drug might also induce body weight gain. OBJECTIVE: The aims of this work were to characterize the pharmacokinetics of amisulpride in order to suggest optimal dosage regimens to achieve the reference range of trough concentrations at steady-state (Cmin,ss) and to describe the relationship between drug pharmacokinetics and prolactin and body weight data. METHODS: The influence of clinical and genetic characteristics on amisulpride pharmacokinetics was quantified using a population approach. The final model was used to simulate Cmin,ss under several dosage regimens, and was combined with a direct Emax model to describe the prolactin data. The effect of model-based average amisulpride concentrations over 24 h (Cav) on weight was estimated using a linear model. RESULTS: A one-compartment model with first-order absorption and elimination best fitted the 513 concentrations provided by 242 patients. Amisulpride clearance significantly decreased with age and increased with lean body weight (LBW). Cmin,ss was higher than the reference range in 65% of the patients aged 60 years receiving 400 mg twice daily, and in 82% of the patients aged > 75 years with a LBW of 30 kg receiving 200 mg twice daily. The pharmacokinetic/pharmacodynamic model included 101 prolactin measurements from 68 patients. The Emax parameter was 53% lower in males compared with females. Model-predicted prolactin levels were above the normal values for Cmin,ss within the reference range. Weight gain did not depend on Cav. CONCLUSIONS: Amisulpride treatment might be optimized when considering age and body weight. Hyperprolactinemia and weight gain do not depend on amisulpride concentrations. Modification of the amisulpride dosage regimen is not appropriate to reduce prolactin concentrations and alternative treatment should be considered.

Cognitive Effects of Combined Amisulpride and Quetiapine Treatment in Patients With Refractory Schizophrenia: A Naturalistic, Prospective Study.

BACKGROUND: Regarding the treatment of patients with resistant schizophrenia, different options exit, although they are supported by limited evidence. In this study, antipsychotic polypharmacy, comprising 1200 mg of amisulpride and 600 mg of quetiapine, was used. Clinical change evaluation was performed using neurocognitive evaluations. STUDY QUESTION: The use of amisulpride and quetiapine will imply a clinical improvement in patients affected by schizophrenia, which will be specially reflected in a cognitive improvement. STUDY DESIGN: Naturalistic and prospective study. Twenty-six patients were applied and assessed by a battery of neurocognitive evaluations since the pretreatment baseline until 6-month treatment. The patients had no biological response to medication, high social maladjustment, and a long clinical history of the disease. Kane and Brenner criteria for treatment-resistant schizophrenia were applied to choose the subjects. MEASURES AND OUTCOMES: The cognitive improvement will imply a significant betterment, from the pretreatment baseline until 6-month treatment, in the following cognitive tests: Stroop Test, WAIS Coding Subtest, and Comprehensive Trail Making Test (CTMT). An improvement in the Calgary Depression Scale, Simpson-Angus Scale, and Visual Analogue Scale (EVA) will also be observed. This scales were been used during the baseline, 3 months after, and then, 6 months. RESULTS: Subjects, after 6-month treatment with amisulpride and quetiapine, did show statistically significant differences in the assessed areas: WAIS Coding Subtest (P < 0.001), CTMT A and B (CTMT A P < 0.034; CTMT B P < 0.000), and Stroop Tests: Word (P < 0.001), Word-Color (P < 0.007), and Interference (P < 0.039). Furthermore, they showed a statistically significant difference in the Calgary Depression Scale (P < 0.002), Simpson-Angus Scale (P < 0.019), and EVA (P < 0.001). CONCLUSIONS: The results of this report show a cognitive and clinical improvement in refractory patients after the administration of amisulpride and quetiapine.