Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

A Comparison of Quality of Life, Medication Side-Effect and Adherence among Schizophrenia Patients on Conventional versus Atypical Antipsychotics

Quality of life (QoL) is becoming a widely accepted schizophrenia management outcome. But it is still not very clear if there are any significant differences between the conventional and atypical antipsychotics in terms of QoL improvement among people with schizophrenia (PWS). It is also imperative that antipsychotic drug-related factors, such as medication adherence and side-effect, which could directly or indirectly affect the QoL of PWS, are determined and compared among PWS on different classes of the drugs. Data were collected on Socio-demographic Characteristics, Quality of Life and Medication adherence using Socio-demographic and Schizophrenia Clinical Characteristics questionnaire, World Health Organization Quality of Life (WHOQoL)-Brief, and Morisky Medication Adherence Scale (MMAS) respectively from 250 respondents attending a tertiary health center’s Psychiatric clinic in Kano, Nigeria. Although PWS on the two classes of antipsychotic drugs showed inequalities in different aspects and domains of QoL, as well as in the levels of adherence and side-effects, the differences were all insignificant. However, presence of drug side effects was significantly associated with lower health-related QoL in the conventional antipsychotics group (p = 0.001), and lower score in the physical domain of QoL in the atypical antipsychotics group (p = 0.044). Medication adherence was found to be associated with better scores in different domains of QoL in both groups of PWS. There are no significant differences in terms of QoL, medication side-effect and adherence among PWS on the two classes of antipsychotics. However, drug side-effects and adherence were significantly and respectively associated with lower and higher scores in different domains of QoL in both groups.

MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Advances in the Study of Antitumor Activity and Mechanism of Antipsychotic Drug Brexpiprazole

Antipsychotics such as phenothiazines,pimozide,flupentixol and brexpiprazole have been shown to have good antitumor effects.Brexpiprazole,the successor to aripiprazole,has a better safety profile.Brexpiprazole promotes the death of tumor cells by inhibiting the prolif-eration of tumor stem cells,resolving the resistance of tumor cells to EGFR-TKIs,and promoting the sensitivity of tumor cells to chemothera-peutic agents,thus inhibiting the development of colorectal,lung,glioblastoma,pancreatic,and gastric cancers.This review focuses on the antitumor effects of antipsychotic drugs,especially the inhibitory effect of brexpiprazole on tumor cells,aiming to provide a theoretical basis for antipsychotic drugs in antitumor field.

Influence of different second generation antipsychotics on the QTc interval: A pragmatic study

AIM To investigate whether differential influence on the QTc interval exists among four second generation antipsychotics(SGAs) in psychosis.METHODS Data were drawn from a pragmatic, randomized headto-head trial of the SGAs risperidone, olanzapine, quetiapine, and ziprasidone in acute admissions patients with psychosis, and with follow-up visits at discharge or maximally 6-9 wk, 3, 6, 12 and 24 mo. Electrocardiograms were recorded on all visits. To mimic clinical shared decision-making, the patients were randomized not to a single drug, but to a sequenceof the SGAs under investigation. The first drug in the sequence defined the randomization group, but the patient and/or clinician could choose an SGA later in the sequence if prior negative experiences with the first one(s) in the sequence had occurred. The study focuses on the time of, and actual use of the SGAs under investigation, that is until treatment discontinuation or change, in order to capture the direct medication effects on the QTc interval. Secondary intention-to-treat(ITT) analyses were also performed. RESULTS A total of 173 patients, with even distribution among the treatment groups, underwent ECG assessments. About 70% were males and 43% had never used antipsychotic drugs before the study. The mean antipsychotic doses in milligrams per day with standard deviations(SD) were 3.4(1.2) for risperidone, 13.9(4.6) for olanzapine, 325.9(185.8) for quetiapine, and 97.2(42.8) for ziprasidone treated groups. The time until discontinuation of the antipsychotic drug used did not differ in a statistically significant way among the groups(Log-Rank test: P = 0.171). The maximum QTc interval recorded during follow-up was 462 ms. Based on linear mixed effects analyses, the QTc interval change per day with standard error was-0.0030(0.0280) for risperidone;-0.0099(0.0108) for olanzapine;-0.0027(0.0170) for quetiapine, and-0.0081(0.0229) for ziprasidone. There were no statistically significant differences among the groups in this regard. LME analyses based on ITT groups(the randomization groups), revealed almost identical slopes with-0.0063(0.0160) for risperidone,-0.0130(0.0126) for olanzapine,-0.0034(0.0168) for quetiapine, and-0.0045(0.0225) for ziprasidone. CONCLUSION None of the SGAs under investigation led to statistically significant QTc prolongation. No statistically significant differences among the SGAs were found.

Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment

Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected throuqh Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings,including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis. Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for long- term azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies,and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.

Antipsychotics cardiotoxicity:What's known and what's next

Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns.These cardiotoxic effects range from arrhythmia to heart failure in the clinic,with myocarditis/cardiomyopathy,ischemic injuries,and unexplained cardiac lesions as the pathological bases.Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity.This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level.We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity.We propose that third-generation antipsychotics or drug adjuvant therapy,such as cannabinoid receptor modulators that confer dual benefits—i.e.,alleviating cardiotoxicity and improving metabolic disorders—deserve further clinical evaluation and marketing.

Audit of physical health monitoring in children and adolescents receiving antipsychotics in neurodevelopmental clinics in Northumberland

AIM To ascertain performance against the standards set by National Institute for Clinical Excellence (NICE) guidelines on physical health monitoring of thirty children and adolescents prescribed antipsychotics in neurodevelopmental clinics in Northumberland and identifying areas for improvement in practice. METHODS The audit involved a review of recorded documentation pertaining to physical health monitoring in patient electronic records pertaining to children and adolescents attending neurodevelopmental clinics in Northumberland prescribed antipsychotics. Clients were also contacted by telephone if relevant documentation could not be identified or retrieved to confirm the details. 32 case notes were perused of which 2 were excluded as they had refused to have venepuncture which was documented in the electronic records. RESULTS The overall audit results demonstrated partial compliance with NICE guidelines on physical health monitoring in children and adolescents prescribed antipsychotics. Bi-annual recording of height, weight, blood pressure, pulse rate and review of side effects was completed in 100% of subjects. However, annual monitoring for blood tests including liver function, renal function full blood count as well as biannual monitoring of serum prolactin, serum lipid profile was completed only in 56% of subjects. Comparative baseline characteristics between the two groups (compliant and non-compliant with guidelines) found no differences based on any socio-demographic or clinical variables. However, the proportion of patients in the group compliant to guidelines was higher in the age group of 12-17 years as compared to < 12 years (70.58% vs 38.46%), though not statistically significant (χ~2 = 1.236; P = 0.24). CONCLUSION Development of tailored and specific guidelines for physical health monitoring in children and adolescents prescribed antipsychotics taking into consideration clinical effectiveness and safety profile is likely to improve adherence rates.

Hydrolysis Process of the Anticancer Agents Novel Non-classical trans-Platinum(Ⅱ) with Aliphatic Amines

The hydrolysis process of the anticancer agents novel non-classical transplatinum（ Ⅱ ） with aliphatic amines and the influence of solvent models therein have been studied by using hybrid density functional theory （B3LYP）. In this study, the stepwise hydrolysis, trans[PtCl2（Am）（isopropylamine）] ＋ 2H2O → trans-[Pt（Am）（isopropylamine）（OH2）2]^2＋＋ 2Cl^-, was explored. Implicit solvent effects were incorporated through polarized continuum models. The stationary points on the potential energy surfaces for the first and second hydrolysis steps,proceeding via a general SN2 pathway, were fully optimized and characterized. It was found that the first hydrolysis reaction is easier than the second one and the hydrolysis of trans- [PtCl2-（isopropylamine）2] is the easiest in our studying systems. The result can assist in under- tanding the hydrolysis mechanism of trans-[PtCl2（Am）（isopropylamine）] and designing novel Pt-based anticancer drugs.

Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics

Accumulating evidence suggests that a disruption of early brain development,in which insulin-like growth factor-2(IGF-2)has a crucial role,may underlie the pathophysiology of schizophrenia.Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia.Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients.Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study.Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS)and serum IGF-2 levels were determined using ELISA.We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline(P<0.05).After 2 months of atypical antipsychotic treatment,a significant improvement in each PANSS subscore and total score was observed in patients(all P<0.01),and the serum IGF-2 levels of patients were significantly increased compared with those at baseline(203.13±64.62 vs.426.99±124.26 ng/mL;t=−5.044,P<0.001).Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms(r=−0.522,P=0.006).Collectively,our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics,suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

A method for stochastic seismic response analysis of non-classically damped structures

A method to calculate the stationary random response of a non-classically damped structure is proposed that features clearly-defined physical meaning and simple expression. The method is developed in the frequency domain. The expression of the proposed method consists of three terms, i.e., modal velocity response, modal displacement response, and coupled (between modal velocity and modal displacement response). Numerical results from the parametric study and three example structures reveal that the modal velocity response term and the coupled term are important to structural response estimates only for a dynamic system with a tuned mass damper. In typical cases, the modal displacement term can provide response estimates with satisfactory accuracy by itself, so that the modal velocity term and coupled term may be ignored without loss of accuracy. This is used to simplify the response computation of non-classically damped structures. For the white noise excitation, three modal correlation coefficients in closed form are derived. To consider the modal velocity response term and the coupled term, a simplified approximation based on white noise excitation is developed for the case when the modal velocity response is important to the structural responses. Numerical results show that the approximate expression based on white noise excitation can provide structural responses with satisfactory accuracy.

Newer antipsychotics: Brexpiprazole, cariprazine, and lumateperone: A pledge or another unkept promise?

Antipsychotic agents are used for various indications in the treatment of psychiatric disorders.Despite their proven roles in multiple conditions,the treatment-emergent side effects of antipsychotic medications,such as metabolic side effects,are often the limiting factor for their long-term and short-term uses.Moreover,antipsychotic medications are often criticized for being less effective in treating different disabling symptoms such as negative symptoms of schizophrenia.As a result,the search for safer and more efficacious antipsychotic agents is ongoing.Newer antipsychotic agents are gaining attention related to emerging efficacy and tolerability data in treating neuropsychiatric conditions.In this review,we attempt to appraise the scientific data on psychopharmacology,safety profile,and efficacy of the newer additions to the list of second-generation antipsychotics,namely brexpiprazole,cariprazine,and lumateperone.We conducted a selective review utilizing PubMed,clinicaltrials.gov,and Cochrane databases to gather appropriate publications,keeping broad inclusion criteria.There were no restrictions on the age of the study population or the year of publication.We also cross-referenced articles and references to capture all existing studies.Our review of the current literature indicates that all three antipsychotic agents appear to be promising based on their short-term studies,while long-term studies remain limited.There is also a need for a head to head comparison between the newer antipsychotics with the other antipsychotic agents to ascertain if the newer agents are any better than the others.

THE ANALYTICAL APPROACH FOR LARGE SCALE NON-CLASSICALLY DAMPED DYNAMIC SYSTEM

This paper gives a dynamic decoupling approach for the analysis of large scale non-classically damped system, in which the complex variable computations were completely avoided not only in solving for the eigenvalue problem but also in the calculation of the dynamic response. The analytical approaches for undamped gyroscopic system, non-classically damped system, including the damped gyroscopic system were unified. Very interesting and useful theoretical results, practical algorithms were obtained which are applicable to both non-defective and defective systems.

Concrete damage diagnosed using the non-classical nonlinear acoustic method

It is known that the strength of concrete is seriously affected by damage and cracking. In this paper, six concrete samples under different damage levels are studied. The experimental results show a linear dependence of the resonance frequency shift on strain amplitude at the fundamental frequency, and approximate quadratic dependence of the am- plitudes of the second and third harmonics on strain amplitude at the fundamental frequency as well. In addition, the amplitude of the third harmonics is shown to increase with the increase of damage level, which is even higher than that of the second harmonics in samples with higher damage levels. These are three properties of non-classical nonlinear acoustics. The nonlinear parameters increase from 106 to 108 with damage level, and are more sensitive to the damage level of the concrete than the linear parameters obtained by using traditional acoustics methods. So, this method based on non-classical nonlinear acoustics may provide a better means of non-destructive testing （NDT） of concrete and other porous materials.

Photon-added and photon-subtracted displaced Fock states and their non-classical properties

A new kind of quantum optical state, photon-added and -subtracted displaced Fock states, is introduced by applying the inverse of bosonic creation and annihilation operators to displaced Fock states. The quantum statistical properties of these states are investigated by numerical methods. Numerical results indicate that these states reveal some interesting non-classical properties, such as anti-bunching effects, sub-Poisson distributions and negativities of their Wigner functions.

Underlying disease may increase mortality risk in users of atypical antipsychotics

Schizophrenia is a group of the most common types of mental illness.Commonly used antischizophrenia drugs all increase mortality to some extent.The increased risk of death in older individuals and patients with dementia using atypical antips-ychotics may be due to myocardial damage,increased mobility and increased risk of stroke.

Finite Element Processes Based on GM/WF in Non-Classical Solid Mechanics

In non-classical thermoelastic solids incorporating internal rotation and conjugate Cauchy moment tensor the mechanical deformation is reversible. This suggests that within the realm of linear mathematical models that only consider small strains and small deformation the mechanical deformation is reversible. Hence, it is possible to recast the conservation and balance laws along with constitutive theories in a form that adjoint A* of the differential operator A in mathematical model is same as the differential operator A. This holds regardless of whether we consider an initial value problem (IVP) (when the integrals over open boundary are neglected) or boundary value problem (BVP). Thus, in such cases Galerkin method with weak form (GM/WF) for BVPs and space-time Galerkin method with weak form (STGM/WF) for IVPs are highly meritorious due to the fact that: 1) the integral form for BVPs is variationally consistent (VC) and 2) the space-time integral forms for IVP are space time variationally consistent (STVC). The consequence of VC and STVC integral forms is that the resulting coefficient matrices are symmetric and positive definite ensuring unconditionally stable computational processes for both BVPs and IVPs. Other benefits of GM/WF and space-time GM/WF are simplicity of specifying boundary conditions and initial conditions, especially traction boundary conditions and initial conditions on curved boundaries due to self-equilibrating nature of the sum of secondary variables that only exist in GM/WF due to concomitant. In fact, zero traction conditions are automatically satisfied in GM/WF, hence need not be specified at all. While VC and STVC feature also exists in least squares process (LSP) and space-time least squares finite element processes (STLSP) for BVPs and IVPs, the ease of specifying traction boundary conditions feature in GM/WF and STGM/WF is highly meritorious compared to LSP and STLSP in which zero traction conditions need to be explicitly specified. A disadvantage of GM/WF and STGM/ WF is that the mathematical models (momentum equations) needed in the desired form contain higher order derivatives of displacements (upto fourth order), hence necessitate use of higher order spaces in their solution. As well known, this problem can be easily overcome in LSP and STLSP by introduction of auxiliary equations and auxiliary variables, thus keeping the highest orders of the derivatives of the dependent variables to one or any other desired order. A serious disadvantage of this approach in LSP is the significant increase in the number of dependent variables, hence poor computational efficiency. In this paper we consider non-classical continuum models for internally polar linear elastic solids in which internal rotations due to displacement gradient tensor (hence internal polar physics) are considered in the conservation and the balance laws and the constitutive theories. For simplicity, we only consider isothermal case;hence energy equation is not part of mathematical model. When using mathematical models derived in displacements in GM/WF and LSP in constructing integral forms, we note that in GM/WF the number of dependent variables is reduced drastically (only three in R3), whereas in case of first order systems used in LSP and STLSP we may have as many as 22 dependent variables for isothermal case. Thus, GM/WF results in dramatic improvement in computational efficiency as well as accuracy when minimally conforming spaces are used for approximations. In this paper we only consider mathematical model in R2 for BVPs (for simplicity). Mathematical models for IVP and BVP in R3 will be considered in subsequent paper. The integral form is derived in R2 using GM/WF. Numerical examples are presented using GM/WF and LSP to demonstrate advantages of finite element process derived using integral form based on GM/WF for non-classical linear theories for solids incorporating internal rotations due to displacement gradient tensor.

Role of antipsychotics for treating behavioral and psychological symptoms of dementia

Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes （NHs） for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the preva-lence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest effcacy in reducing symptoms of aggression and psychosis in dementia, there is insuffcient evidence to routinely rec-ommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.