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).

Thirty years of scientific research on second-generation antipsychotic drugs in Japan: A bibliometric analysis

Aims:Research on second-generation antipsychotic drugs (SGAs) has experienced great development in last decades.We did a bibliometric study on the scientific publications on SGAs in Japan.Methods: With theEMBASEandMEDLINEdatabases, we chose papers published from Japan with SGA descriptors. Price’s law and Bradford’s law has been used as bibliometric indicators for quantitating production and dispersion, respectively, of published papers on SGAs. We also calculated the participation index of different countries, and correlated those bibliometric data with some social and health data from Japan (such as totalper capitaexpenditure on health and gross domestic expenditure on research and development). Results: A sum of 669 original documents were published from Japan from 1982 to 2011. Those results fulfilled Price’s law, with scientific production on SGAs showing exponential growth (correlation coefficientr= 0.9261, as against anr= 0.8709 after linear adjustment). The most studied SGAs in Japan wererisperidone (n= 192), aripiprazole (n= 109), and olanzapine (n= 106). Division of documents into Bradford zones yielded a nucleus occupied exclusively by theProgress in Neuro-Psychopharmacology and Biological Psychiatry(49 articles). Those publications were in 157 different journals. Seven of the first 10 frequently used journals had an impact factor of being greater than 3. Conclusions: The SGA publications in Japan have been through exponential growth over the studied period, without evidence of reaching a saturation point.

Aging effects on QT interval： Implications for cardiac safety of antipsychotic drugs

Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy： ＂QT interval＂ or ＂QT＂ and ＂age＂ or ＂aging＂. The entry criteria were： over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate （QTc） and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation 〉 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.

Genomics of schizophrenia and pharmacogenomics of antipsychotic drugs

Antipsychotic drugs are the neuroleptics currently used in the treatment of schizophrenia (SCZ) and psychotic disorders. SCZ has a heritability estimated at 70% - 90%;and pharmacogenomics accounts for 60% - 90% variability in the pharmacokinetics and pharmacodynamics of psychotropic drugs. Personalized therapeutics based on individual genomic profiles in SCZ entails the characterization of 5 types of gene clusters and their related metabolomic profiles: 1) genes associated with disease pathogenesis;2) genes associated with the mechanism of action of drugs;3) genes associated with drug metabolism (phase I and II reactions);4) genes associated with drug transporters;and 5) pleiotropic genes involved in multifaceted cascades and metabolic reactions. Genetic studies in SCZ have revealed the presence of chromosome anomalies, copy number variants, multiple single-nucleotide polymorphisms of susceptibility distributed across the human genome, aberrant single-nucleotide polymorphisms in microRNA genes, mitochondrial DNA mutations, and epigenetic phenomena. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variation in specific candidate genes and the positive and adverse effects of drug treatment. Approximately 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4. About 10% - 20% of Western populations are defective in genes of the CYP superfamily. Only 26% of Southern Europeans are pure extensive metabolizers for the trigenic cluster integrated by the CYP2D6 + CYP2C19 + CYP2C9 genes. Efficacy and safety issues in the pharmacological treatment of SCZ are directly linked to genetic clusters involved in the pharmacogenomics of antipsychotic drugs and also to environmental factors. Consequently, the incorporation of pharmacogenomic procedures both to drugs under development and drugs on the market would help to optimize therapeutics in SCZ and other central nervous system disorders.

The Effect of Several Commonly Used Antipsychotic Drugs on the Renal Function of Patients with Mental Illness

Objective: To understand the effects of several commonly used antipsychotics on the renal function of patients with mental illness. Method: Collected patients with mental illness who were hospitalized in our hospital from January 2020 to June 2021, and selected as the research subjects patients with psychiatric disorders who were treated with 2 kinds of commonly used antipsychotic drugs;and collected 3 ml of venous blood before treatment and one month after treatment for renal function tests;observed the changes of renal function indexes before and after treatment. Results: In the collected 694 patients with mental illness, before using antipsychotic drugs, the renal function indexes were BUN: 4.42 ± 1.92 mmol/l;Cr: 70.97 ± 16.92 μmol/l;CCr: 88.37 ± 21.07 ml/min;β2-MG: 1.67 ± 0.61 mg/L;UA: 359.90 ± 112.82 μmol/l;CYS-C: 0.92 ± 0.24 mg/L. One month after using antipsychotics, BUN: 3.77 ± 1.37 mmol/l;Cr: 70.46 ± 16.71 μmol/l;CCr: 87.78 ± 20.63 ml/min;β2-MG: 1.75 ± 0.64 mg/L;UA: 332.53 ± 91.48 umol/l;CYS-C: 0.92 ± 0.24 mg/L;the renal function indexes of urea nitrogen, β2 microglobulin, uric acid and other items all changed significantly. The differences before and after treatment were statistically significant, P < 0.01. Conclusion: Several commonly used antipsychotic drugs have a greater impact on the renal function of patients with mental illness. During the treatment, the changes in renal function should be monitored regularly, if severe renal damage is found, the treatment plan or dosage should be adjusted in time to avoid endangering life.

Classical Neurotransmitters and Neuropeptides Involved in Schizophrenia： How to Improve the Therapeutic Effect of the Antipsychotic Drugs

We describe the alterations of classical neurotransmitters and neuropeptides in schizophrenia. In this disease, susceptibility genes encode GABA （gamma-aminobutyric acid） and glutamate hypofunction and dopamine hyperactivity. A neural network is developed in the mesolimbic system, the hippocampus and the prefrontal cortex. According to this neural network, dopamine and serotonin hyperactivity might be due to a reduced presynaptic inhibition through GABAergic and glutaminergic neurons. A survey of the therapeutic and adverse effects of commonly prescribed and of recently developed second-generation antipsychotic drugs is given The interaction with other specific subreceptors of classical neurotransmitters and neuropeptides is suggested to improve the antipsychotic effect. In the treatment of schizophrenia, pharmacotherapy should be combined with psychoeducation. Accordingly, a recurrence of psychotic symptoms could be prevented in a long-term treatment.

Inhibitory Effect of 5-Adenylic Acid on Bitter Taste of Antipsychotic Drugs

The purpose of the present study was to examine the effect of adenylic acid (adenosine 5-monophosphate;AMP), a known nutritional enhancer, on inhibiting the bitterness of antipsychotic medicines administered to patients with mental illnesses, including children. First, we chose four antipsychotic medicines, amitriptyline hydrochloride (AMT), chlorpromazine hydrochloride (CPZ), haloperidol (HPD) and risperidone (RIS) and evaluated the inhibition of their bitterness by AMP through taste sensor measurements. AMP showed a significant bitterness inhibition effect on all drugs. Second, MarvinSketch analysis revealed the potential formation of electrostatic interactions between ionic forms (IV) of AMP and ionic (cationic) forms of each drug, which resulted in bitterness suppression. Third, chemical shift perturbations in 1H-NMR studies suggested an interaction between the phosphate group of AMP and amino group of AMT, CPZ, HPD and RIS. Last, conventional elution experiments of up to 1 min simulating oral cavity conditions were performed for 1 whole AMT tablet, half AMT tablet, crushed half AMT tablet, and crushed AMT tablet containing AMP powder/solution (1, 3 mM potency). The taste sensor output values of the crushed AMT tablet containing AMP powder/solution (1, 3 mM potency) were significantly lower than those of the crushed tablet.

Interaction of antipsychotic drug with novel surfactants: Micellization and binding studies

The interaction of cationic gemini surfactants(alkanediyl-α,ω-bis(alkyl dimethylammonium bromide)) with an antipsychotic drug(chlorpromazine hydrochloride(CPZ)) has been investigated. Various micellar and interfacial parameters have been deliberated by surface tension measurement to report the nature of interactions between drug and novel surfactant mixtures. The behavior of mixed systems, their compositions and activities of components have been analyzed in the light of Rubingh's theory. The results indicate synergism in the binary mixtures.The binding study between CPZ and surfactants has been done by spectroscopic techniques such as UV–visible and fluorescence. The results are discussed in the light of the use of gemini surfactants as promising drug delivery agents for phenothiazine drugs, and hence, improve their bioavailability.

Trajectories of response in schizophrenia-spectrum disorders: A one-year prospective cohort study of antipsychotic effectiveness

BACKGROUND Antipsychotic drugs remain the mainstay of schizophrenia treatment;however,their effectiveness has been questioned,and it is not possible to predict the response to a specific antipsychotic drug in an individual patient.Thus,it is important to compare the effectiveness of the various antipsychotics and search for possible response predictors.AIM To investigate the effectiveness of antipsychotic drugs,we examined response trajectories and predictors for belonging to different trajectory groups.METHODS The Bergen-Stavanger-Innsbruck-Trondheim(BeSt InTro)trial compared the effectiveness of three atypical antipsychotics-amisulpride,aripiprazole,and olanzapine-in a prospective,semirandomized,rater-blind,head-to-head design.Adult participants with a schizophrenia spectrum disorder diagnosis,according to international classification of diseases,Tenth Revision(ICD-10)F20–29,were included.Participants were followed for a period of 12 mo,with assessments at baseline;after one,three and six weeks;and after three,six,nine and 12 mo.A latent class mixed model was fitted to our data.The three-trajectory model based on the Positive and Negative Syndrome Scale(PANSS)total score reduction was found to have adequate fit,and the study drugs,as well as various demographic and clinical parameters,were tested as predictors for belonging to the different trajectory groups.RESULTS Overall,144 participants were included,and 41%completed the 12-mo study period.The largest trajectory group,consisting of 74%of participants,showed a PANSS total score reduction of 59%from baseline to 12 mo(Good response group).A trajectory group comprising 13%of participants had their PANSS total score reduced by 82.5%at 12 mo(Strong response group),while the last response trajectory group comprising 13%of the participants had a PANSS total score reduction of 13.6%(Slight response group).The largest part of the total reduction for the Good and Strong response groups occurred at six weeks of treatment,amounting to 45%and 48%reductions from baseline,respectively.The use of amisulpride predicted belonging to the Strong response group,while unemployment,depression,and negative psychotic symptoms at baseline increased the chance of belonging to the Slight response group,indicating a poor response to antipsychotic drug treatment.CONCLUSION Most of the participants(87%)had a good outcome after one year.Amisulpride users,more often than aripiprazole and olanzapine users,belonged to the response trajectory group with a strong response.

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.

Antipsychotic Medication and Risk of QTc Prolongation: Focus on Multiple Medication and Role of Cytochrome P450 Isoforms

Objective: To identify the effects of antipsychotics on QTc prolongation in light of age, gender, antipsychotic combination pattern, antipsychotic doses and cytochrome P450 (CYP) mediation, using large database describing the antipsychotic treatment of patients with schizophrenia in Japan. Methods: Using database of 4176 patients with schizophrenia discharged between April 2004 and March 2005 and receiving outpatient treatment from 526 psychiatric hospitals in Japan. Of the patients, 1437 were included for the analysis. These patients were classified into three groups according to the antipsychotic CPZ-equivalent doses that they received (low, 1 - 299 mg;middle, 300 - 999 mg;and high, ≥1000 mg). QTc intervals ≥ 440 msec were considered prolonged. We reviewed all the package inserts of the antipsychotics used from the website of Pharmaceuticals and Medical Devices Agency. Results: The mean QTc interval of the total patient group was 410.4 ± 23.3 msec. The females had significantly higher QTc values than the males (414.5 ± 24.0 vs. 406.8 ± 22.2 msec, respectively;p 0.05). Logistic regression analysis revealed that female gender (odds ratio [OR] = 1.83;95% CI: 1.28 - 2.56), CYP3A4-metabolized drugs (OR 1.56;95% CI: 1.05 - 2.30) were associated with an increased risk of QTc prolongation. Conclusion: The co-prescription of CYP3A4-mediated antipsychotic drugs should be carefully considered in females due to potential risk of QTc prolongation. Further studies of the cardiovascular safety of antipsychotics are warranted in patients receiving multiple medications.

Environmental pollution with psychiatric drugs

Among all contaminants of emerging interest,drugs are the ones that give rise to the greatest concern.Any of the multiple stages of the drug's life cycle(production,consumption and waste management)is a possible entry point to the different environmental matrices.Psychiatric drugs have received special attention because of two reasons.First,their use is increasing.Second,many of them act on phylogenetically highly conserved neuroendocrine systems,so they have the potential to affect many non-target organisms.Currently,wastewater is considered the most important source of drugs to the environment.Furthermore,the currently available wastewater treatment plants are not specifically prepared to remove drugs,so they reach practically all environmental matrices,even tap water.As drugs are designed to produce pharmacological effects at low concentrations,they are capable of producing ecotoxicological effects on microorganisms,flora and fauna,even on human health.It has also been observed that certain antidepressants and antipsychotics can bioaccumulate along the food chain.Drug pollution is a complicated and diffuse problem characterized by scientific uncertainties,a large number of stakeholders with different values and interests,and enormous complexity.Possible solutions consist on acting at source,using medicines more rationally,eco-prescribing or prescribing greener drugs,designing pharmaceuticals that are more readily biodegraded,educating both health professionals and citizens,and improving coordination and collaboration between environmental and healthcare sciences.Besides,end of pipe measures like improving or developing new purification systems(biological,physical,chemical,combination)that eliminate these residues efficiently and at a sustainable cost should be a priority.Here,we describe and discuss the main aspects of drug pollution,highlighting the specific issues of psychiatric drugs.

Development of two different pharmacogenomics detection methods for second-generation antipsychotic drugs quetiapine and aripiprazole

Objective:Second-generation antipsychotics are widely used in mental illness,but the treatment effects and side effects are affected by single nucleotide polymorphisms(SNPs)of related genes.Quetiapine and aripiprazole are two frequently used secondgeneration antipsychotic drugs.The aim of this study was to develop two different SNP detection methods for four SNP alleles associated with the pharmacokinetics of quetiapine and aripiprazole,based on high-resolution melting(HRM)and multicolor melting curve assay(MMCA)respectively.Methods:Whole genome DNA samples were obtained from 240 healthy people(107 females and 133 males)without genetic diseases.HRM methods were established using four kinds of specific primers and a saturated fluorescent dye.Each SNP allele with their own primers was detected in a single reaction.In the MMCA method,a multiplex polymerase chain reaction with 4 different-colored fluorescent probes was established to detect four SNP alleles in a single reaction.All experimental protocols were approved by the Ethics Committee of the Shanghai Children’s Medical Center,China(SCMC-201015)on November 22,2010.Results:Two detection methods for the pharmacogenomics of quetiapine and aripiprazole,based on HRM and MMCA respectively,were established in this study.The single-target HRM method can be completed in 96 minutes,whereas the quadruplex MMCA method takes 133 minutes.It was found that the results of HRM and MMCA for the four SNP alleles had 100%coincidence with Sanger sequencing in the 240 samples.Conclusion:This study developed two methods for the detection of four pharmacogenomic SNP alleles that correlated with quetiapine and aripiprazole.Both methods are rapid,cost-saving,highly accurate and potentially facilitate rational use of second-generation antipsychotics for clinical medication.

8种抗精神病药、13种抗抑郁药及9种活性代谢物在人血清中的稳定性研究

目的研究8种抗精神病药(阿立哌唑、氨磺必利、奥氮平、喹硫平、利培酮、帕利哌酮、氯氮平、氯丙嗪)、13种抗抑郁药(阿米替林、安非他酮、度洛西汀、多虑平、氟伏沙明、氟西汀、氯米帕明、米氮平、帕罗西汀、曲唑酮、舍曲林、文拉法辛、西酞普兰)及9种活性代谢物(脱氢阿立哌唑、脱烷基喹硫平、去甲氯氮平、去甲替林、羟安非他酮、去甲多虑平、去甲氟西汀、去甲氯米帕明、O-去甲文拉法辛)在人血清中的稳定性,为这些药物在实施治疗药物监测过程中的样本传输、检测、存储条件的确定以及质控血清、标准曲线校准血清保存条件和保存期限的确定提供参考数据。方法以混合健康人血清为基质配制质控血清,进行稳定性考察,分别考察目标药物及活性代谢产物在室温(12 h、24 h、72 h)、2~8℃冷藏(2 d、5 d、7 d)、-80℃超低温(14个月)保存及3次反复冻融的稳定性。采用超高效液相色谱-串联质谱法检测被分析物的血清浓度。结果安非他酮在室温、2~8℃冷藏保存条件下质控血清测得浓度的负偏倚>40%,但在-80℃超低温保存14个月及3次反复冻融条件下测得浓度的偏倚均在±15%内。其他药物及代谢物在各考察条件下测得浓度的偏倚均在±15%内。但在室温条件下,随着放置时间延长,脱烷基喹硫平、度洛西汀、氟伏沙明、舍曲林、氟西汀、去甲氟西汀、去甲替林、阿米替林、氯丙嗪、氯米帕明及去甲氯米帕明测得浓度的负偏倚逐渐增加。结论在人血清基质中,安非他酮在室温和2~8℃冷藏的条件下不稳定。其余8种抗精神病药、12种抗抑郁药及9种活性代谢物在室温下可稳定72 h,但在室温下存放超24 h后,部分药物存在降解趋势,建议放入2~8℃的冰箱中保存,在此条件下可稳定至少7 d。本文所研究的所有药物及活性代谢物的质控血清可在-80℃冰箱中保存至少14个月,3次反复冻融不影响其稳定性。

大黄三味片治疗抗精神病药药物性便秘临床观察

目的探讨大黄三味片治疗抗精神病药药物性便秘的有效性和安全性。方法收集2020年7月至2022年12月沈阳市精神科卫生中心精神科病房符合抗精神病药药物性便秘诊断标准的120例患者,按照随机数字法分为治疗组和对照组,每组60例,治疗组予大黄三味片治疗,对照组予乳果糖口服溶液。观察两组患者治疗前后便秘症状积分,排便时间,腹痛评分(VAS),大便性状改善时间、停药7 d内排便次数及生活质量评分。结果两组治疗有效率对比无统计学差异(P>0.05);治疗组大便性状改善时间短于对照组、停药7 d的排便次数多于对照组(均P<0.05);治疗后,治疗组便秘症状评分、腹痛评分、排便时间低于对照组,生活质量评分高于对照组(均P<0.05)。结论大黄三味片治疗抗精神病药药物性便秘临床疗效确切,有效减轻患者痛苦,停药后疗效持久,两组患者均未见不良反应,安全有效。

重复经颅磁刺激联合抗精神病药物治疗精神分裂症的临床效果分析

目的:分析重复经颅磁刺激联合抗精神病药物治疗精神分裂症的临床效果。方法:选取2023年1—6月潍坊市精神卫生中心收治的精神分裂症患者85例作为研究对象,随机分为对照组(n=43)和试验组(n=42)。对照组采用抗精神病药物治疗,试验组在对照组基础上采用重复经颅磁刺激治疗。比较两组治疗效果。结果:治疗后,两组阳性症状、阴性症状、一般精神症状评分低于治疗前,且试验组低于对照组,差异有统计学意义(P<0.05)。治疗后,两组睡眠质量评分低于治疗前,且试验组低于对照组,两组日常生活能力评分高于治疗前,且试验组高于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:重复经颅磁刺激联合抗精神病药物治疗精神分裂症的效果显著,可改善患者临床症状,提高患者睡眠质量、日常生活能力,且安全性较高。

奥氮平所致恶性综合征1例

目的探讨1例奥氮平所致恶性综合征的临床诊断及治疗方法。方法选取2023年2月11日~3月2日收治的1例恶性综合征患者为研究对象,为临床医师合理诊断提供参考。结果该患者服用非典型抗精神病药物奥氮平之后,出现高热、肌酸激酶升高、震颤及肌张力增高等临床表现,诊断为恶性综合征,立即停药,同时对症治疗,最终好转出院。结论抗精神病药物所致恶性综合征(NMS)是一种罕见且极为严重的不良反应,需要及时发现并尽早停药,对症治疗。

强α_(1)受体拮抗的非典型抗精神病药物导致精神分裂症患者自感发热不适1例

本文报道了1例精神分裂症患者服用强α_(1)受体拮抗的非典型抗精神病药物奥氮平、利培酮、帕利哌酮和氯氮平后出现自感身体发热不适,考虑系药物副反应,换用阿立哌唑后,患者自感发热不适消失。该病例报道旨在提示精神科医生关注强α_(1)受体拮抗的非典型抗精神病药物导致的副反应,并需结合药物作用机制、患者的病理生理、个体差异等综合考虑,提高患者的治疗依从性,改善预后。

益气养阴法治疗抗精神病药物抗胆碱能不良反应临床观察

目的使用益气养阴法治疗抗精神病药物的抗胆碱能不良作用,观察其临床疗效。方法将31例长期服用抗精神病药物,出现抗胆碱能不良作用的患者随机分为治疗组和对照组,其中治疗组17例,以益气养阴法为治则辨证治疗;对照组14例,予常规护理治疗,比较2组治疗疗效。结果治疗1个月后,治疗组抗胆碱能症状量表评分总有效率、中医证型量表评分总有效率与对照组比较,差异有显著统计学意义(P<0.01)。结论使用益气养阴法治疗抗精神病药物的抗胆碱能不良反应能有效改善患者症状表现,且在中西医维度上、各细化证型相互比较疗效近似,该治疗方法尚有进一步提高的空间。