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Objective: To determine if the cardiac function and "endocrinium" of Chinese patients are associated with dopamine D 2 ( DRD2 ) ( rs6276 ) and DRD3 ( rs6280, rs963468 ) genetic polymorphisms when treated with amisulpride., Methods: This study enrolled 148 patients with schizophrenia who took amisulpride orally for 8 weeks. DRD2 (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms were detected with TaqMan-MGB allelic discrimination., Results: Analysis by multivariate covariance analysis (MANCOVA) showed that after adjusting for age, gender, and the baseline level, the increase in the level of aspartate aminotransferase (AST) and creatine kinase (CK) in the rs6276 AG group was higher than that in the AA and GG groups. Similarly, the changed estradiol (E 2 ) level in rs6276 GG and rs963468 GG groups was higher than that in the other two groups. Adjusting for covariates, the increased triglyceride (TG) level in rs6276 GG and rs963468 GG groups was the highest among their different genotype groups. The increase in the level of "AST" in the rs6280 TT group was higher than that in the CC and CT groups upon adjusting for covariates. Similarly, MANCOVA showed that the increase in the level of "CK" in the rs6280 CT group was higher than that in the CC and CT groups. Besides, the increased level of "PRL" in the rs6280 CC group and rs963468 GG group was higher than that in their other two genotypes groups., Conclusion: DRD2 ( rs6276 ) and DRD3 ( rs6280, rs963468 ) polymorphisms can affect amisulpride tolerability since they are associated with the observed adverse reactions, including cardiac dysfunction and endocrine disorders in Chinese patients with schizophrenia., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Extensive research has been undertaken to predict treatment response (TR) to antipsychotics. Most studies address TR to antipsychotics in general and as monotherapy, however, it is unknown whether patients might respond favourably to a combination of antipsychotics., Aims: This study aimed to identify differential predictors for TR to monotherapy with amisulpride or olanzapine compared to a combination of antipsychotics., Methods: Post-hoc analysis was conducted of data collected from the COMBINE-study, a double-blind, randomized, controlled trial. Demographic and disease-related measures were gathered at baseline to predict TR after eight weeks defined by the Positive and Negative Syndrome Scale. Missing values were accounted for by a random replacement procedure. Attrition effects and multicollinearity were analysed and sets of logistic regression models were calculated for different treatment groups., Results: Of the 321 randomized patients, 201 completed procedures until week eight and 197 were included in the analyses. For all treatment groups, early TR after two weeks and high subjective well-being under antipsychotics at baseline were robust predictors for TR. The propensity for early side effects also indicated a higher risk of later non-response. Specific parameter estimates were rather similar between treatment groups., Conclusion: Early TR, drug-related subjective well-being, and early side effect propensity evolved as predictors for later TR whether to monotherapy or combination strategy. Accordingly, due to a lack of differential predictors, early and close monitoring of targeted and unwanted effects is indicated to guide respective treatment decisions., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Harmaline is one of the β-carboline derivative compounds that is widely distributed in the food chain and human tissues. Harmine, a dehydrogenated form of harmaline, appeared to have a higher concentration in the brain, and appeared to be elevated in essential tremor (ET) and Parkinson's disease. Exogenous harmaline exposure in high concentration has myriad consequences, including inducing tremor, and causing neurodegeneration of Purkinje cells in the cerebellum. Harmaline-induced tremor is an established animal model for human ET, but its underlying mechanism is still controversial. One hypothesis posits that the inferior olive-cerebellum pathway is involved, and CaV 3.1 T-type Ca 2+ channel is a critical target of action. However, accumulating evidence indicates that tremor can be generated without disturbing T-type channels. This implies that additional neural circuits or molecular targets are involved. Using in vitro slice Ca 2+ -imaging and patch clamping, we demonstrated that harmaline reduced intracellular Ca 2+ and suppressed depolarization-induced spiking activity of medium spiny striatal neurons (MSN), and this effect of harmaline can be partially attenuated by sulpiride (5 µM). In addition, the frequencies of spontaneous excitatory post-synaptic currents (sEPSCs) on MSNs were also significantly attenuated. Furthermore, the induced tremor in C57BL/6 J mice by harmaline injections (i.p. 12.5-18 mg/kg) was also shown to be attenuated by sulpiride (20 mg/kg). This series of experiments suggests that the dorsal striatum is a site of harmaline toxic action and might contribute to tremor generation. The findings also provide evidence that D2 signaling might be a part of the mechanism underlying essential tremor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The challenges posed by treatment-resistant schizophrenia and depressive symptoms have led to ongoing difficulties despite the availability of antipsychotics and antidepressants. This review addresses the potential of amisulpride analogs, particularly SEP-4199, in addressing these challenges through enhanced efficacy and reduced side effects., Areas Covered: This review focuses on the pharmacological profile of amisulpride analogs, exemplified by LB-102 and its derivative SEP-4199. PubMed gathered articles (up to 10 March 2023) on 'amisulpride,' 'schizophrenia,' 'bipolar disorder,' and 'major depressive disorder;' ClinicalTrials.gov tracked SEP-4199 and LB-102 trials. LB-102, a newly identified N-methylated analog of amisulpride, exhibits enhanced lipophilicity at lower doses, as demonstrated in a phase 1 study, indicating significant promise for therapeutic applications. The discovery of SEP-4199, a non-racemic analog composed of R - and S-enantiomers in an 85:15 ratio, is discussed, emphasizing its potential to enhance antidepressant effects while minimizing extrapyramidal side effects via selective D2 receptor binding. Recent phase 2 trials have demonstrated SEP-4199's efficacy in treating depressive symptoms in bipolar disorder I, capitalizing on D2-mediated anti-anhedonic and D3-mediated reward effects., Expert Opinion: The development of SEP-4199 presents a potential breakthrough for managing depressive symptoms in bipolar disorder I. Further exploration of D2 and D3 receptor-mediated effects could lead to improved treatment strategies.

Background: Anhedonia is a frequent cause of functional im p airment in psychosis. Although it is plausible that medication-induced D2 receptor blockade could diminish hedonic responding, there is little experimental research testing this hypothesis in humans., Methods: To inspect possible effects of partial D2 blockade on hedonic experiences, we administered 300 mg of Amisulpride or placebo to 85 participants in a randomized, double-blind, placebo-controlled trial. Participants were then subjected to an emotional evocation task utilizing standardized pictorial pleasant, neutral, and unpleasant stimuli., Results: We observed lower positivity ratings in the Amisulpride group compared to placebo across all stimulus categories (p = .026, f = 0.25) and no group differences in negativity or arousal ratings. The Amisulpride group also showed lower electrodermal responses across all stimulus categories compared to placebo (p = .017, f = 0.27). The electrodermal response was especially diminished for pleasant stimuli., Conclusion: We interpret our findings as evidence that D2 blockade via Amisulpride can reduce at-the-moment hedonic responsivity in healthy volunteers. If these results can be confirmed in drug-naïve clinical samples, this would indicate that antipsychotic medication contributes to clinical anhedonia, probably via antagonistic effects at the dopamine D2 receptor., Competing Interests: Declaration of competing interest We have no conflict of interest to report. We declare that no third-party funding was utilized for this project. Costs of the study were covered exclusively by regular university funds from the universities of Marburg and Hamburg. Therefore, there was no influence of funding on study design; data collection; data analysis and interpretation; writing of the report; or on the decision to submit this report for publication., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We present a case of a 23-year-old male Caucasian patient admitted to the emergency department because of an acute onset of difficulty of articulation, weakness of the left arm, throat- and neck pain. An emergency CT & MRI of the brain showed no abnormalities. The Patient had started visiting a new neurologist three weeks before admission and received Sulpiride against Tourette syndrome (TS) in a rapid escalation manner over a short period. Sulpiride induced dystonia and other neurological symptoms that were clinically masked by dystonic and clonic tics of the known TS. 5 mg Biperiden (anticholinergic agent) was slowly injected intravenously under monitor condition. The Patient reported an immediate disappearance of articulation difficulties, left arm movement, and cervical and neck pain. After discontinuing Sulpiride the patient did not develop such attacks anymore and could be discharged the next day. This case shows the development of dystonia in correlation to the use of Sulpiride, which involved the cervical region, the laryngeal muscles, and the left upper extremity. Our case is of particular interest to neurologists and psychiatrists, because of their involvement in the treatment of TS. Therefore, young neurologists must be aware of such complications when thinking of differential diagnosis in movement disorders particularly in TS., Competing Interests: Die Autorinnen und Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use., Objectives: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019)., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials., Data Collection and Analysis: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification., Main Results: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I 2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I 2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome., Authors' Conclusions: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Aims: Amisulpride, a first-line schizophrenia treatment, has shown large interindividual variability in plasma/serum levels, often outside the reference range (100-320 ng/mL). This study aims to clarify the impact of dose, sex, age and related factors for the interpatient variability in amisulpride plasma/serum concentration., Methods: Both English and Chinese databases were searched from their inception to May 16, 2019, using the terms: amisulpride and (plasma OR serum OR blood OR "drug monitoring" OR concentration). Studies reporting concentrations and either a dose, associated factor, clinical outcome or side effect were included., Results: Fourteen studies with 1628 participants were eventually included. Eligible articles yielded data on drug concentration and dose, averaging 333.9 (95% confidence interval [CI]: 294.5-373.3) ng/mL and 636.2 (95% CI: 549.7-722.6) mg/d, respectively. The calculated mean concentration-to-dose (C/D) ratio was 0.60 (95% CI: 0.52-0.67) (ng/mL)/mg. Subgroup analysis suggested that female patients on combined lithium-amisulpride have higher concentration levels and C/D ratios. Age was slight positive associated with C/D ratio while not for plasma level. Smoker patients have high concentration level than nonsmoking patients but not for C/D. Responsive and nonresponsive groups did not differ in concentration and C/D., Conclusion: Pooled concentration levels of amisulpride were higher than recommended with wide individual variation, especially in older patients, female patients and patients taking amisulpride combined with lithium. The specific therapeutic reference range for amisulpride may require reconstruction, which should consider the influence of age, sex, kidney function, drug-drug interactions, different dose regimens and sampling times in future study., (© 2020 The British Pharmacological Society.)

Purpose: Discontinuation of offending drugs can prevent drug-induced parkinsonism (DIP) before it occurs and reverse or cure it afterwards. The aim of this study was to investigate the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide claims data., Materials and Methods: We selected DIP patients of ages ranging from 40 to 100 years old with the G21.1 code from the Korean National Service Health Insurance Claims database from 2009 to 2015. The annual standardized prevalence of DIP was explored from 2009 to 2015. Trends were estimated using the compound annual growth rate (CAGR) and the Cochran-Armitage test for DIP over the course of 6 years. Additionally, the utilization of offending drugs was analyzed., Results: The annual prevalence of DIP was 4.09 per 100000 people in 2009 and 7.02 in 2015 (CAGR: 9.42%, p <0.001). Levosulpiride use before and after DIP diagnosis showed a clear trend for decreasing utilization (CAGR: -5.4%, -4.3% respectively), whereas the CAGR for itopride and metoclopramide increased by 12.7% and 6.4%, respectively. In 2015, approximately 46.6% (858/1840 persons) of DIP patients were prescribed offending drugs after DIP diagnosis. The most commonly prescribed causative drug after DIP diagnosis was levosulpiride., Conclusion: The prevalence of DIP has increased. To prevent or decrease DIP, we suggest that physicians reduce prescriptions of benzamide derivatives that have been most commonly used, and that attempts be made to find other alternative drugs. Additionally, the need for continuing education about offending drugs should be emphasized., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

One of the possible long-term consequences of antipsychotic-induced hyperprolactinemia is the development of pituitary tumors - prolactinomas. So far, two pharmacovigilance studies of spontaneous adverse event report databases have suggested an increased risk, whereas a longitudinal study carried out with risperidone showed no evidence of increased risk of tumors with mass effect. Besides, information on amisulpride and paliperidone is lacking. Thus, in this study, we aimed to analyze the European pharmacovigilance database (EudraVigilance) to shed light on this issue. We searched for all suspected spontaneous cases of pituitary tumors associated with antipsychotics in EudraVigilance up to 23 March 2017. To assess the association between pituitary tumor cases and each antipsychotic, we calculated the proportional reporting ratios. Among 4 964 866 events of all types recorded in EudraVigilance, we found 292 cases of pituitary tumors associated with antipsychotics. All atypical antipsychotics except clozapine fulfilled the criteria to generate a safety signal. The highest proportional reporting ratio values were found for amisulpride 51.57 (36.3-73.2), risperidone 21.83 (18.4-25.8), and paliperidone 19.95 (14.7-27.1). Sulpiride and haloperidol showed a higher risk among typical antipsychotics 12.4 (5.89-26.1) and 7.0 (4.35-11.3). Notably, we found that a mass effect was present in 16% of the cases. Besides, 18 cases occurred in patients aged below 18 years. Our analysis of the data in EudraVigilance confirms the safety signal detected by previous studies. Interestingly, for the first time, we show that the association seems to be the strongest for amisulpride and that a mass effect was present in around 16% of the cases.

A 53-year-old woman, known case of diabetes mellitus and rheumatoid arthritis, presented with a 4-day history of hyperthermia, rigidity, tremor and altered sensorium. She developed these symptoms after having been administered parenteral levosulpiride to control vomiting due to secondary adrenal insufficiency. We managed her as a case of life-threatening neuroleptic malignant syndrome (NMS) requiring mechanical ventilation, bromocriptine and other supportive care. She subsequently recovered and was discharged in a stable condition. To the best of our knowledge, this is the first documented case report describing levosulpiride-induced NMS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Levosulpiride is a newer prokinetic agent with increasingly extensive use in India by general physicians. Levosulpiride selectively inhibits gut and central D2 receptors and is associated with various movement disorders like- tremor, Parkinsonism, dyskinesias and rarely dystonia. We report 7 cases of levosulpirideinduced dystonia at our institute. Though all patient had at least 50% improvement after discontinuation of levosulpiride, none had complete recovery at mean follow up of 5.5 months. Through this article we want to highlight extrapyramidal side effects of levosulpiride, need of its awareness among physicians., (© Journal of the Association of Physicians of India 2011.)

The clinical presentation of a young woman with galactorrhoea is described in detail including the history and clinical examination findings. While the patient and her family members feared a serious medical condition which had so far been an obscurity despite a number of investigations, we tried to diagnose the patient starting from the basics, which after a proper history revealed a levosulpiride-induced galactorrhoea. This again lays emphasis on the old adage in medical field that 'a proper history and examination are the key to diagnosis'. There are few reports pertaining to levosulpiride-induced galactorrhoea making it a rare side effect of this drug. We further try to discuss the different causes of galactorrhoea in a young non-pregnant woman which can be encountered in clinical practice., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

This study aimed to evaluate pregnancy outcomes of women who were inadvertently exposed to levosulpiride in early pregnancy. All 162 consecutive singleton pregnant women counselled through the Korean Motherisk Program, Cheil General Hospital, between April 2001 and April 2014, on teratogenic risk after inadvertent exposure to levosulpiride in early pregnancy were enrolled in this study. The women were exposed to levosulpiride at median 4.8 gestational weeks. The rate of miscarriage was not significantly different between groups (9.2% in those exposed and 5.5% in the non-exposed; p = .084). The rate of major malformations was not significantly different between exposed (2.7%) and non-exposed pregnancies (4.4%) (p = .481). All other pregnancy outcomes between the two groups were comparable (p > .05). Our data suggest that levosulpiride causes no significant adverse effects on pregnancy outcomes and therefore may be not a major teratogen.

Objective: To investigate the clinical effects of aripiprazole on sexual dysfunction induced by amisulpride or risperidone in male patients with schizophrenia., Methods: This study included 75 male patients with drug-induced secondary sexual dysfunction after treated with amisulpride or risperidone for first-episode schizophrenia between October 2014 and October 2016. We substituted aripiprazole for amisulpride or risperidone, gradually increased the dose from 10 to 30 mg/d within 2 weeks, and maintained 30 mg/d from the 3rd week. At 4 and 8 weeks after medication, we evaluated the sexual function of the patients, measured the levels of serum prolactin (PRL) and testosterone (T), obtained the scores of the Positive and Negative Symptoms Scale (PANSS), recorded adverse reactions, and compared the parameters with those before aripiprazole administration., Results: Compared with pre-aripiprazole administration, the patients showed significant increases after 4 weeks of medication in the sexual function score (24.3 ± 2.1 vs 32.6 ± 3.6, P <0.05) and T level (［13.3 ± 2.7］ vs ［17.4±3.0］ mmol/L, P <0.05) but a decreased level of PRL (［38.5 ± 10.5］ vs ［27.9 ± 8.2］ ng/ml, P <0.05). At 8 weeks, the sexual function score and serum PRL were both restored to the baseline levels at admission, and the erectile function score, ejaculation score, total score, and serum T level even exceeded the baseline, though with no statistically significant differences (P >0.05). In comparison with pre-aripiprazole administration, the PANSS score was significantly decreased at 4 weeks after medication (62.1 ± 4.9 vs 57.2 ± 5.5, P <0.05) and even lower at 8 weeks (51.2 ± 5.2) (P <0.05). The incidence rates of medication-related excitation, dizziness, insomnia, and loss of appetite were 6.7%, 5.3%, 4.0% and 1.3% respectively, and no other serious adverse reactions were observed., Conclusions: Aripiprazole is effective for the treatment of drug-induced sexual dysfunction in schizophrenic men by continuously alleviating their positive and negative symptoms and meanwhile improving their sexual function and restoring their sexual hormone levels.

Objective: We have previously reported high dopamine D2/3 receptor occupancies at low amisulpride concentrations in older people with Alzheimer's disease (AD), during off-label treatment of AD-related psychosis. This post hoc analysis explored pharmacokinetic (concentration) and pharmacodynamic (prolactin, D2/3 occupancy) contributions to symptom reduction and extrapyramidal side effects (EPS) to inform AD-specific dose adjustments., Methods: Population pharmacokinetic-pharmacodynamic models were developed by combining pharmacokinetic data from a phase 1 study in 20 healthy older people with pharmacokinetic prolactin, [¹⁸F]fallypride D2/3 receptor imaging, and clinical outcome data from 28 older patients prescribed open amisulpride (25-75 mg/d) to treat AD-related psychosis. Model predictions were used to simulate dose-response and dose-EPS., Results: Symptom reduction (delusions) was associated with amisulpride concentration (P = 1.3e-05) and D2/3 occupancy (P < .01, caudate, putamen, thalamus). Model predictions suggested that across concentrations of 40-100 ng/mL, and occupancies of 40% to 70% in the caudate and thalamus and 30% to 60% in the putamen, there was a 50% to 90% probability of response and < 30% probability of EPS. Simulations, based on concentration-delusions and concentration-EPS model outputs, showed that 50 mg/d of amisulpride was the appropriate dose to achieve this target range in those aged > 75 years; increasing the dose to 75 mg/d increased the risk of EPS, particularly in those aged > 85 years of low body weight., Conclusions: These findings argue strongly for the consideration of age- and weight-based dose adjustments in older patients with AD-related psychosis and indicate that 50 mg/d of amisulpride may be both the minimal clinically effective dose and, in those aged > 75 years, the maximally tolerated dose., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Background: Between 40% and 70% of people with treatment-resistant schizophrenia do not respond to clozapine, despite adequate blood levels. For these people, a number of treatment strategies have emerged, including the prescription of a second anti-psychotic drug in combination with clozapine., Objectives: To determine the clinical effects of various clozapine combination strategies with antipsychotic drugs in people with treatment-resistant schizophrenia both in terms of efficacy and tolerability., Search Methods: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (to 28 August 2015) and MEDLINE (November 2008). We checked the reference lists of all identified randomised controlled trials (RCT). For the first version of the review, we also contacted pharmaceutical companies to identify further trials., Selection Criteria: We included only RCTs recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug., Data Collection and Analysis: We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and 95% confidence intervals (CI) on an intention-to-treat basis using a random-effects meta-analysis. For continuous data, we calculated mean differences (MD) and 95% CIs. We used GRADE to create 'Summary of findings' tables and assessed risk of bias for included studies., Main Results: We identified two further studies with 169 participants that met our inclusion criteria. This review now includes five studies with 309 participants. The quality of evidence was low, and, due to the high degree of heterogeneity between studies, we were unable to undertake a formal meta-analysis to increase the statistical power.For this update, we specified seven main outcomes of interest: clinical response in mental state (clinically significant response, mean score/change in mental state), clinical response in global state (mean score/change in global state), weight gain, leaving the study early (acceptability of treatment), service utilisation outcomes (hospital days or admissions to hospital) and quality of life.We found some significant differences between clozapine combination strategies for global and mental state (clinically significant response and change), and there were data for leaving the study early and weight gain. We found no data for service utilisation and quality of life. Clozapine plus aripiprazole versus clozapine plus haloperidolThere was no long-term significant difference between aripiprazole and haloperidol combination strategies in change of mental state (1 RCT, n = 105, MD 0.90, 95% CI -4.38 to 6.18, low quality evidence). There were no adverse effect data for weight gain but there was a benefit of aripiprazole for adverse effects measured by the LUNSERS at 12 weeks (1 RCT, n = 105, MD -4.90, 95% CI -8.48 to -1.32) and 24 weeks (1 RCT, n = 105, MD -4.90, 95% CI -8.25 to -1.55), but not 52 weeks (1 RCT, n = 105, MD -4.80, 95% CI -9.79 to 0.19). Similar numbers of participants from each group left the study early (1 RCT, n = 106, RR 1.27, 95% CI 0.72 to 2.22, very low quality evidence). Clozapine plus amisulpride versus clozapine plus quetiapine One study showed a significant benefit of amisulpride over quetiapine in the short term, for both change in global state (Clinical Global Impression (CGI): 1 RCT, n = 50, MD -0.90, 95% CI -1.38 to -0.42, very low quality evidence) and mental state (Brief Psychiatric Rating Scale (BPRS): 1 RCT, n = 50, MD -4.00, 95% CI -5.86 to -2.14, low quality evidence). Similar numbers of participants from each group left the study early (1 RCT, n = 56, RR 0.20, 95% CI 0.02 to 1.60, very low quality evidence) Clozapine plus risperidone versus clozapine plus sulpirideThere was no difference between risperidone and sulpiride for clinically significant response, defined by the study as 20% to 50% reduction in Positive and Negative Syndrome Scale (PANSS) (1 RCT, n = 60, RR 0.82, 95% CI 0.40 to 1.68, very low quality evidence). There were similar equivocal results for weight gain (1 RCT, n = 60, RR 0.40, 95% CI 0.08 to 1.90, very low quality evidence) and mental state (PANSS total: 1 RCT, n = 60, MD -2.28, 95% CI -7.41 to 2.85, very low quality evidence). No-one left the study early. Clozapine plus risperidone versus clozapine plus ziprasidoneThere was no difference between risperidone and ziprasidone for clinically significant response (1 RCT, n = 24, RR 0.80, 95% CI 0.28 to 2.27, very low quality evidence), change in global state CGI-II score (1 RCT, n = 22, MD -0.30, 95% CI -0.82 to 0.22, very low quality evidence), change in PANSS total score (1 RCT, n = 16, MD 1.00, 95% CI -7.91 to 9.91, very low quality evidence) or leaving the study early (1 RCT, n = 24, RR 1.60, 95% CI 0.73 to 3.49, very low quality evidence). Clozapine plus ziprasidone versus clozapine plus quetiapineOne study found, in the medium term, a superior effect for ziprasidone combination compared with quetiapine combination for clinically significant response in mental state (> 50% reduction PANSS: 1 RCT, n = 63, RR 0.54, 95% CI 0.35 to 0.81, low quality evidence), global state (CGI - Severity score: 1 RCT, n = 60, MD -0.70, 95% CI -1.18 to -0.22, low quality evidence) and mental state (PANSS total score: 1 RCT, n = 60, MD -12.30, 95% CI -22.43 to -2.17, low quality evidence). There was no effect for leaving the study early (1 RCT, n = 63, RR 0.52, CI 0.05 to 5.41, very low quality evidence)., Authors' Conclusions: The reliability of results from this review is limited, evidence is of low or very low quality. Furthermore, due to the limited number of included studies, we were unable to undertake formal meta-analyses. As a consequence, any conclusions drawn from these findings are based on single, small-sized RCTs with high risk of type II error. Properly conducted and adequately powered RCTs are required. Future trialists should seek to measure patient-important outcomes such as quality of life, as well as clinical response and adverse effects.

Aim: The D 2 /D 3 antagonist amisulpride has shown promising efficacy against postoperative nausea and vomiting (PONV) at low doses. We investigated whether intravenous amisulpride has an effect on the QTc interval in a formal Thorough QT study (TQT)., Methods: This was a randomized, double-blind, placebo and positive-controlled, four-way crossover study. Forty healthy Caucasian and Japanese subjects were included to receive a single administration of 5 mg and 40 mg of i.v. amisulpride or a single oral dose of moxifloxacin or placebo per period., Results: The therapeutic dose of 5 mg amisulpride was associated with a slight, transient increase in mean ΔΔQTcF, from 2.0 ms prior to dosing to a peak of 5 ms (90% CI: 2.8, 7.1 ms) at 8 min, decreasing to 2.1 ms at 30 min after dosing. The supra-therapeutic dose of 40 mg given at twice the infusion rate was associated with prolongation in ΔΔQTcF peaking at 23.4 ms (90% CI: 21.3, 25.5 ms) at the end of infusion (8 min), returning below 10 ms within 1.5 h. Assay sensitivity was confirmed; ΔΔQTcF had increased by 12.3 ms (90% CI 10.1, 14.6 ms) at 4 h post-dose. The PK-PD relationship revealed no differences between Caucasian and Japanese subjects (p-value > 0.5)., Conclusions: Amisulpride has a plasma concentration-dependent effect on the QTc interval. The proposed therapeutic dose for management of PONV does not lead to a prolongation of QTcF above the threshold of regulatory concern, while such effect could not be excluded for the supratherapeutic dose., (© 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years., Objectives: To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia., Search Methods: We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics., Data Collection and Analysis: Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence., Main Results: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness., Authors' Conclusions: Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.

Sulpiride and ethylene glycol monomethyl ether (EGME) are known ovarian toxicants that stimulate prolactin (PRL) secretion, resulting in hypertrophy of the corpora lutea and increased progesterone (P4) production. The purpose of the present study was to investigate how the PRL stimulatory agents affected uterine carcinogenesis and to clarify the effects of PRL on endometrial adenocarcinoma progression in rats. Ten-week-old female Donryu rats were treated once with N-ethyl-N'-nitro-N-nitrosoguanidine (20 mg kg(-1) ), followed by treatment with sulpiride (200 ppm) or EGME (1250 ppm) from 11 weeks of age to 12 months of age. Sulpiride treatment inhibited the incidence of uterine adenocarcinoma and precancerous lesions of atypical endometrial hyperplasia, whereas EGME had no effect on uterine carcinogenesis. Sulpiride markedly prevented the onset of persistent estrus throughout the study period, and EGME delayed and inhibited the onset of persistent estrus. Moreover, sulpiride-treated animals showed high PRL and P4 serum levels without changes in the levels of estradiol-17β, low uterine weights and histological luteal cell hypertrophy. EGME did not affect serum PRL and P4 levels. These results suggest that the prolonged low estradiol-17β to P4 ratio accompanied by persistent estrous cycle abnormalities secondary to the luteal stimulatory effects of PRL may explain the inhibitory effects of sulpiride on uterine carcinogenesis in rats. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Purpose: The study aimed to evaluate the comparative risk of oral ulcerations among antipsychotic medications., Methods: We analyzed the National Health Insurance Research Database of Taiwan and included patients newly initiated with a single antipsychotic agent including haloperidol, sulpiride, olanzapine, quetiapine, risperidone, or amisulpride during 2002 to 2010. The outcome of interest was oral ulceration, defined by the presence diagnoses of stomatitis and mucositis, aphthous-like ulceration and oral burns, or dispensing of stomatological corticosteroids included triamcinolone, dexamethasone, hydrocortisone, and prednisolone. We conducted Cox proportional hazards regression to compare the risks of oral ulceration among antipsychotics., Results: The rate of oral ulcerations was highest in the amisulpride group (217.7 per 1000 person-year), followed by quetiapine (193.9 per 1000 person-year), olanzapine (161.9 per 1000 person-year), sulpiride (147.1 per 1000 person-year), risperidone (115.6 per 1000 person-year), haloperidol (107.5 per 1000 person-year) and aripiprazole (49.8 per 1000 person-year). Compared with haloperidol users, the adjusted hazard ratio (AHR) was 1.40 (95% CI, 1.12-1.73) in olanzapine, 1.48 (95% CI, 1.30-1.69) in quetiapine, 1.27 (95% CI, 1.19-1.44) in sulpiride, 1.68 (95% CI, 0.97-2.59) in amisulpride, 1.02 (95% CI, 0.83-1.45) in risperidone, and 0.41 (95% CI, 0.24-0.72) in aripiprazole users by Cox regression model., Conclusion: Olanzapine, quetiapine, and sulpiride posed a higher risk, while aripiprazole posed a lower risk of oral ulcerations compared with haloperidol in subjects with newly initiated antipsychotic therapy. Risperidone and amisulpride tended to have higher risk of oral ulcerations, but this was not statistically significant., (Copyright © 2015 John Wiley & Sons, Ltd.)

Importance: Weight gain is a common and serious adverse effect of antipsychotic treatment. A variable individual predisposition to development of metabolic disturbances calls for predictive biological markers., Objectives: To investigate whether attenuated striatal activity during reward anticipation is associated with amisulpride-induced weight change in antipsychotic-naive patients with schizophrenia undergoing initial treatment and to examine the association between weight change and changes in reward anticipation activity after treatment., Design, Setting, and Participants: Sixty-nine antipsychotic-naive inpatients and outpatients with schizophrenia were included in a multimodal longitudinal cohort study from December 16, 2008, to December 11, 2013. Fifty-eight patients underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. After 6 weeks of treatment with amisulpride, a relatively selective dopamine D2 antagonist, 39 patients underwent a second fMRI scan and measurement of change in body weight. Final follow-up was completed on January 14, 2014, and data were analyzed from October 25, 2014, to June 15, 2015 and August 31 to September 19, 2015., Exposures: Six weeks of individually dosed amisulpride treatment., Main Outcomes and Measures: Reward-anticipation activity in the striatum before and after treatment and weight change., Results: Of the 69 patients who consented to the study, 39 underwent the follow-up fMRI and weight measurement (age range, 18-45 years; 17 women and 22 men). The mean (SD) daily dose of amisulpride was 272 (168; range, 50-800) mg, and patients gained a mean (SD) of 2.3 (2.8; range, -4 to 8) kg in body weight. Improvement from baseline to follow-up was found on the mean (SD) positive (19.9 [4.1] to 14.3 [3.8]), general (39.7 [7.7] to 30.5 [7.7]), and total (78.5 [15.3] to 63.2 [13.9]) scores on the Positive and Negative Syndrome Scale (P < .001). Weight gain was predicted by low mean (SD) baseline reward-related activity in the right-sided putamen (0.20 [0.93]; F35,3 = 5.64; P = .003). After 6 weeks, weight gain was associated with an increase in mean (SD) reward activity in the same region during treatment (0.28 [0.74]; F37,1 = 4.48; P = .04)., Conclusions and Relevance: Activity in striatal regions of the reward system appears to be associated with the individual variability in the predisposition for antipsychotic-associated weight gain. Moreover, pharmacologic modulation of the reward system may play a role in antipsychotic-associated weight gain.

Objective: The aim of this study was to highlight the use of combined intravenous lipid emulsion (ILE) and plasma exchange (PE) therapies in multidrug toxicity., Clinical Presentation and Intervention: A 45-year-old woman who attempted suicide by ingesting large quantities of amisulpride (28 g), diazepam (250 mg), valsartan (2,240 mg), aripiprazole (45 mg) and paliperidone (21 mg) was taken to the hospital of Adnan Menderes University School of Medicine. Upon arrival, she exhibited signs of cardiotoxicity and severe depression of the central nervous and respiratory systems. She was treated successfully with ILE for 4 h and PE therapy for 36 h, consecutively. She was discharged on the fourth day of hospitalization having fully recovered., Conclusion: The patient was successfully treated with the combination of ILE and PE., (© 2016 S. Karger AG, Basel.)

Objective: Heat stroke is a medical emergency. Psychiatric patients are particularly susceptible to heat stroke. Therefore, awareness and preventive measures of heat stroke are important for both clinicians and patients. Case description A 49-year-old man with schizophrenia, who was under maintenance treatment with olanzapine 20 mg/day, trihexyphenidyl 4 mg/day, and trazodone 50 mg/day, suffered from heat stroke in a heat wave and required intensive care. He recovered with the medical treatment provided. Discussion Several factors could have contributed to the impaired thermoregulation and the occurrence of heat stroke in this case: schizophrenia, the psychotropic regimen, and lack of preventive measures. Possible differential diagnoses of heat stroke in this case include infection, neuroleptic malignant syndrome, and serotonin syndrome., Conclusion: Heat stroke can occur during the maintenance treatment of olanzapine, trihexyphenidyl, and trazodone for schizophrenia. Clinicians should be proactive to reduce the risk of heat stroke in psychiatric patients.

Purpose: The aim of this study was to characterize the pharmacokinetic (PK) properties and assess the safety profiles of different formulations of levosulpiride in healthy Chinese volunteers., Methods: Levosulpiride was administered to 42 healthy male and female (1:1) subjects in tablet (PO) and injectable (IM and IV) dosage forms. Blood samples were collected at regular intervals after single and multiple drug administration. The concentration of levosulpiride in plasma was determined by a validated liquid chromatography tandem mass spectrometry method. Noncompartmental analysis was performed to estimate PK parameters. One-way ANOVA was used to test for linearity and assess the effect of sex on the PK properties of the drug. Adverse effects were monitored using investigators' questionnaires and subjects' spontaneous reports, vital sign measurements, hematology, clinical chemistry, and electrocardiography., Findings: Levosulpiride exhibited linear pharmacokinetic properties over the dose range of 25 to 100 mg by PO route and 25 to 75 mg by IM route. The corresponding mean AUC0-t increased from 449 to 1443 ng/h/mL and from 2874 to 7559 ng/h/mL, respectively. After repeated PO and IM administration, steady state was reached on day 4 of multiple dosing with accumulation index of 1.8 and on day 2 of multiple dosing with accumulation index of 1.3, respectively. The bioavailability of levosulpiride via IM and PO routes was 96.8% and 23.4%, respectively. No significant differences were observed on PK properties between male and female subjects. More than half (23 of 42 [54.8%]) of healthy volunteers experienced one or more adverse events in total, including constipation, diarrhea, drowsiness, skin rash, and extrapyramidal reactions., Implications: The regimen of 50-mg levosulpiride tablets 3 times daily and 50-mg levosulpiride injection (IM) twice daily provided similar accumulation coefficient, and the former reached steady state much more slowly. The bioavailability of levosulpiride after oral administration was poor and the absorption rate was slower compared with IM administration, which imply delayed clinical efficacy for patients with dyspepsia or neuropsychiatric disorders. On multiple dosing, levosulpiride exhibited poor tolerability with high incidence of adverse reactions. There was no need to adjust administration regimen based on sex. ClinicalTrials.gov Identifier: NCT02481583., (Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.)

Objective: This prospective study sought to compare the acute effects of haloperidol, amisulpride, and quetiapine on serum markers of bone formation and resorption in relatively young patients with minimal previous exposure to antipsychotic drugs., Methods: Patients included in the study were randomly assigned to receive haloperidol, amisulpride, or quetiapine monotherapy in an open-label manner. Serum osteocalcin (OC, a marker of bone formation), C-terminal peptide of type I collagen (CTX, a marker of bone resorption), prolactin (PRL), estradiol, and testosterone were measured in 70 patients at baseline and after 4 weeks of antipsychotic treatment., Results: A repeated-measures analysis of variance revealed a significant difference in CTX levels and in the OC to CTX ratio between treatment groups (F = 4.481, P < 0.05; F = 8.114, P < 0.01). After 4 weeks of treatment, only the amisulpride group had significantly increased CTX levels and decreased OC/CTX. In addition, an obvious increase in PRL level and a reduction of sex hormone secretion after amisulpride treatment were found. No significant changes in bone turnover were observed in the haloperidol or quetiapine groups. Notably, a positive correlation between the CTX change to the change in PRL after treatment (r = 0.255, P < 0.05) was observed., Conclusions: The PRL-raising antipsychotic drug amisulpride influenced bone turnover balance very early in the course of treatment, which may require long-term monitoring of bone metabolism. Bone resorption marker changes induced by acute antipsychotic drug treatment are likely related to increased PRL levels.

Objective: Amisulpride is a second-generation antipsychotic agent indicated for the treatment of schizophrenia and other major psychotic illnesses. Amisulpride-induced bradycardia is a rare condition of unknown etiology and mechanism. Asymptomatic bradycardia has been associated with amisulpride in only two cases. In our case, the association was rated as "probable" on the Naranjo adverse drug reaction probability scale., Method: Case report., Results: A 45-year-old male patient developed symptomatic bradycardia during usage of amisulpride (400-800 mg/day), which dramatically improved after the complete termination of amisulpride usage. The psychiatric condition remained relatively stable without bradycardia after administration of another antipsychotic agent [risperidone (3 mg/day)]., Conclusion: This is the first case report of symptomatic bradycardia associated with the use of amisulpride. Although bradycardia is a rare adverse reaction to antipsychotics, this finding may alert psychiatrists and physicians to this antipsychotic drug side effect. Further study is needed to disclose the role of antipsychotics in bringing about symptomatic bradycardia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A course of dihydroquercetin (antioxidant) injections to 5-month-old Wistar rats with sulpiride-induced benign prostatic hyperplasia led to reduction of proliferative activity in the glandular structures and to attenuation of the inflammatory reaction in the tissue. Prostatic antioxidant/prooxidant balance returned to normal after the treatment.

Background/purpose: The USA Food and Drug Administration (FDA) issued warnings regarding the use of antipsychotics in patients with dementia in 2003 and 2005. We aimed to study the dose and duration of antipsychotic treatment in dementia, and to examine whether physicians' prescription behaviors changed after the FDA warnings., Methods: Medical charts of outpatients who had Alzheimer's disease, vascular dementia, or mixed dementia were reviewed. Patients must have achieved a clinically stable state for at least 4 weeks after receiving antipsychotic treatment for agitation or psychosis. Demographics, clinical correlates, and duration of antipsychotic treatment were compared among different antipsychotic groups. Because the quetiapine group had the largest sample size, the optimal dose and duration of quetiapine treatment were compared among three time periods (before 2003, 2003-2005, after 2005)., Results: Stable state was achieved in 215 patients (80 had Alzheimer's disease, 117 vascular dementia, and 18 mixed dementia). Most patients (177) took quetiapine, 25 took risperidone, and 13 took sulpiride. The whole sample had a long total duration of antipsychotic treatment (median 525 days, mean 707 days). The median dose and total duration of antipsychotic treatment were 1.0mg/day and 238 days for risperidone, 100mg/day and 390 days for sulpiride, and 25mg/day and 611 days for quetiapine, respectively. The optimal dose and total duration of quetiapine treatment decreased significantly after FDA warning in 2005, although the duration remained long., Conclusion: The optimal doses of antipsychotics were not higher than those of western reports, but the total duration of antipsychotic treatment was quite long. Although our study suggests the prescription dosage and duration of antipsychotic treatment decreased significantly after FDA warning in 2005, the duration of treatment was still long. Given the serious safety concerns, more effort should be made to avoid unnecessary and prolonged prescription., (Copyright © 2012. Published by Elsevier B.V.)

Background: The antipsychotic drug amisulpride has not yet been officially approved for use in the Netherlands, although it is already available in other European countries , including Belgium, the UK and Germany. However, a fast-track procedure has recently been initiated so that amisulpride will soon become available in the Netherlands as well., Aim: To summarise the efficacy and side effects of amisulpride., Method: We discuss the evidence presented in the scientific literature., Results: The scientific literature assures us that amisulpride is an effective antipsychotic drug with an acceptable range of side-effects. This means that there are two main advantages that ensue from the use of amisulpride: a patient's psychosis is more likely to go into remission and patients are less likely to stop taking the drug., Conclusion: The availability of amisulpride in the Netherlands will constitute a valuable addition to the pharmacotherapeutic options for treating psychotic disorders in our county.

Purpose: A case of rapid-onset mania after initiating amisulpride in a patient with schizophrenia and cerebral disease is reported., Summary: A 19-year-old Taiwanese man had a 1-year history of schizophrenia, paranoid type, and cerebral palsy. His only medication was a 12-week course of risperidone 6 mg orally daily. His positive symptoms of auditory hallucinations and paranoid delusions improved markedly, but negative symptoms of inattention, avolition, and anhedonia continued. His motor disability and athetosis of the hand related to cerebral palsy also worsened during risperidone therapy. After a discussion with the patient's guardian, conversion of antipsychotic therapy from risperidone to amisulpride was commenced. On days 1-8 of the conversion, amisulpride 400 mg was given orally daily. The daily risperidone dose on days 1, 2, and 3 was 6, 4, and 2 mg, respectively; risperidone was discontinued after day 3. On day 4, the patient exhibited a euphoric mood, with persistent laughing, expansive self-esteem, extreme talkativeness, flight of ideas, distractibility, and psychomotor agitation. On day 8, the amisulpride dosage was increased to 800 mg orally daily and his manic symptoms worsened. On day 17, amisulpride was withheld and risperidone 4 mg daily was resumed. The manic symptoms subsided within three days after the cessation of amisulpride. The patient was maintained on risperidone 4 mg daily for six months without any further hypomanic or manic symptoms., Conclusion: A 19-year-old man with schizophrenia and underlying cerebral disease developed rapid-onset mania after risperidone was replaced with amisulpride. The reaction resolved soon after amisulpride was discontinued and treatment with risperidone was reinstituted., (Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Objective: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia., Methods: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole) was prescribed for 12 months as appropriate. BMD and PRL were tested before and after treatment. Same measures were conducted in 90 matched healthy controls., Results: Baseline BMD of postero-anterior L1-L4 range from 1.04 ± 0.17 to 1.42 ± 1.23, and there was no significant difference between the patients group and healthy control group. However, post-treatment BMD values in patients (ranging from 1.02 ± 0.15 to 1.23 ± 0.10) were significantly lower than that in healthy controls (ranging from 1.15 ± 0.12 to 1.42 ± 1.36). The BMD values after conventional antipsychotics were significantly lower than that after atypical antipsychotics. The PRL level after conventional antipsychotics (53.05 ± 30.25 ng/ml) was significantly higher than that after atypical antipsychotics (32.81 ± 17.42 ng/ml). Conditioned relevance analysis revealed significant negative correlations between the PRL level and the BMD values after conventional antipsychotics., Conclusion: The increase of PRL might be an important risk factor leading to a high prevalence of osteoporosis in patients with schizophrenia on long-term conventional antipsychotic medication.

Purpose: Previous studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects., Materials and Methods: Patients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA) was employed to efficiently identify potential causal relationships while controlling for potential selection bias., Results: A total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46-2.06) and hyperprolactinemia (12.04; 1.59-91.2). In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment., Conclusions: We found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including stomatological, dermatological, and musculoskeletal or joint side effects, constipation, and pneumonia.