第二代抗精神病药与代谢综合征的概述

第二代（也称非典型）抗精神病药（the second—generation antipsychofice,SGAs）问世极大的改善了抗精神病治疗的有效性和耐受性,尤其是对精神分裂症患者。但越来越多的研究证实SGAs与患者的体重增加、糖尿病、高甘油三酯血症等有关,     

第二代抗精神病药的安全性

介绍第二代抗精神病药较常见不良反应的研究进展。     

脂联素、瘦素与抗精神病药致脂代谢紊乱的相关研究

目的探讨脂联素和瘦素与抗精神病药物致脂代谢紊乱的关系。方法测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、脂联素(Adi)和瘦素(leptin)水平,测量身高和体质量,采用聚合酶链扩增和限制性片段长度多态性技术测定脂联素基因多态性。结果 (1)治疗前后对比,BMI、TG、LDL、Leptin和TC水平均显著增高(P<0.01,P<0.05),而Adi水平则显著降低(P<0.05);(2)治疗后,脂联素基因+45G/X基因型者BMI、TG和LDL较治疗前均显著升高(P<0.01),Adi较治疗前则显著下降(P<0.05),而T/X基因型者治疗前后各项指标无显著变化(P>0.05)。结论抗精神病药物可引起体内脂联素水平降低和瘦素水平升高;脂联素+45位G基因是抗精神病药物致脂代谢紊乱的一个危险因素     

抗精神病药物对首发精神分裂症患者血清瘦素、脂联素和胰岛素的影响

目的探讨抗精神病药物对首发精神分裂症患者血清瘦素、脂联素和胰岛素的影响,及Leptin、Adi和INS在抗精神病药源性肥胖发病中的作用。方法对40名健康查体人员和80例首发精神分裂症患者分别进行了血清Leptin、Adi和INS等项目测定,血清Leptin、Adi采用放射免疫法,血清INS采用电化学发光分析法。结果①首发精神分裂症患者在治疗前其体质量指数、腰臀围比值及血清Leptin、Adi、INS水平与对照组相比均无显著性差异(P>0.05)。治疗10周~12周后,患者组BMI、WHR及血清Leptin、INS水平均明显上升,与治疗前相比差异有显著性(P<0.01);血清Adi水平则明显下降,与治疗前相比差异有显著性(P<0.01)。②患者组在治疗后BMI与血清Leptin、INS水平呈显著正相关(P<0.01),与血清Adi水平呈显著负相关(P<0.01);血清Leptin水平与INS呈显著正相关(P<0.01),与血清Adi水平呈显著负相关(P<0.01);血清Adi水平与INS呈显著负相关(P<0.01)。结论抗精神病药物治疗的精神分裂症患者可发生药源性肥胖,治疗后Leptin和INS水平升高及Adi水平降低,是出现肥胖的原因之一。     

不同第二代抗精神病药物对精神分裂症患者心率变异性影响

目的 探讨氯氮平、利培酮、齐拉西酮和奥氮平四种药物对精神分裂症患者心率变异性的影响.方法 将165例精神分裂症患者随机分入氯氮平、利培酮、齐拉西酮和奥氮平治疗组.采用24小时动态心电图在治疗前和治疗8周末分别检测各组的心率变异性(Heart rate variability,HRV)参数变化.结果 治疗8周末与基线期相比,氯氮平组心率显著加快[(86.4±11.8)vs.(76.3±8.1)];氯氮平和齐拉西酮组SDNN值、SDANN、PNN50值显著降低,而利培酮及奥氮平组SDNNI值、PAN50值、rMSSD值显著增高,差异均有统计学意义.结论 在对心率变异性的影响上,奥氮平、利培酮明显优于齐拉西酮和氯氮平,有更好的心脏保护作用.     

第二代抗精神病药对慢性精神分裂症患者的治疗作用

目的：探讨第1代抗精神病药（FGA）联合与未联合第2代抗精神病药（SGA）对慢性精神分裂症患者临床疗效、认知功能及社会功能的影响。方法：74例慢性精神分裂症患者被随机分为联合组和对照组,联合组为FGA联合SGA,对照组则为持续应用FGA,治疗至少12周。采用简明精神病量表（BPRS）分别于治疗前后评估患者临床疗效,以探究性眼动检测来评估患者的认知功能,采用个人和社会功能量表（PSP）评估社会功能。结果：探究性眼动检测治疗前凝视点数联合组显著低于对照组（P〈0.05）;尽管经过联合SGA治疗后两组间凝视点数虽不存在差异（P〉0.05）,但联合组治疗前后的凝视点数增加值却显著好于对照组（P〈0.001）;反应性探索（RSS）评分在疗前、疗后两组间均差异无显著性。所有联合SGA患者在治疗后PSP评分均显著优于未联合用药组（P〈0.05或P〈0.001）;LSD分析提示：尤以联合利培酮或阿立哌唑对患者PSP评分改善最为显著（P均〈0.001）。结论：联合SGA对慢性精神分裂症患者疗效显著,尤其对患者认知和社会功能改善明显。     

第二代抗精神病药

介绍了第二代抗精神病药的作用机理、临床应用和安全性。     

脂联素在抗精神病药导致体重增加中的作用研究进展

<正>精神分裂症具有高致残率,治疗方法以抗精神病药物为主。体重增加是非典型抗精神病药(second generation antipsychotics,SGAs)的常见副作用,超重的精神分裂症患者罹患心血管疾病风险增高^[1]。脂联素(adiponectin,APN)由脂肪细胞分泌,具有减轻体重、调控炎症、改善糖脂代谢等作用。众多研究发现,脂联素在抗精神病药导致体重增加中发挥重要作用^[2],炎症、基因多态性、DNA甲基化、性激素等影响APN对体重增加的作用,但目前研究结论并不一致,其     

第二代抗精神病药致静坐不能的研究进展

目前第二代抗精神病药物(SGAs)广泛用于各类精神病治疗,与第一代抗精神病药物(FGAs)比较,引起锥体外系副反应(EPSEs)比较少[1],但是SGAs并不是没有EPSEs,通常认为与FGAs有关EPSEs也同样与SGAs有关联.在所有的EPSEs里,本文着重关注静坐不能,一个抗精神病药物和其他一些药物引起的最常见的、致残的药物副反应之一[2].本文对第二代抗精神病药物所致静坐不能的发生率、病理生理学、最新的治疗进展等文献作一综述,以提高对静坐不能的重视.     

第二代抗精神分裂症药物对体重与代谢的影响

目的评价首发精神分裂症单一使用第二代抗精神病药物治疗对体重和代谢的影响。方法采用历史性队列研究方法评估62例首发精神分裂症单一使用抗精神病药物治疗2,4周末体重和代谢改变,并且对这些患者2年后的体重和代谢情况进行随访。结果62例患者随着治疗延长,体重迅速明显增加,平均体重从基线时的（55．5±15．6）kg,第2周末增加至（56．2±15．1）kg,第4周末进一步增加至（57．3±15．0）kg。第二代抗精神病药物对体重均有影响,其中奥氮平（增加5．24％）最为突出,利培酮（增加2．6％）、喹硫平（增加2．1％）次之。治疗第4周末,部分患者的糖脂代谢出现异常。在治疗2年后共随访到47例患者,其中27例继续治疗,20例因各种原因中断治疗,其中6例患者因为体重增加而停药。持续治疗的患者中,体重全部增加,半数体重增加10％～30％,1例患者体重增加50％。结论第二代抗精神病药物在首发精神分裂症急性期治疗会影响体重和糖脂代谢,进而影响患者的躯体健康和服药依从性。     

Investigation of molecular serum profiles associated with predisposition to antipsychotic-induced weight gain

Objectives. Metabolic disturbances are major adverse side effects in the treatment of schizophrenia patients with antipsychotics. A substantial proportion of patients discontinue treatment with second-generation antipsychotics due to weight gain. The objective of this study was to investigate molecular factors predisposing patients to the development of such metabolic disturbances. Methods. We investigated whether serum molecules measured before treatment initiation were associated with subsequent weight gain following a 6-week treatment with antipsychotics. The concentrations of 191 molecules were measured longitudinally in serum from 77 schizophrenia patients using multiplex immunoassays. Results. This showed that the levels of 10 serum molecules at T0 were significantly associated with ΔBMI, which included interleukin-6 receptor, epidermal growth factor and thyroid stimulating hormone. Conclusions. Our results suggest that patients who experience antipsychotic-induced weight gain have specific molecular alterations already prior to treatment. Further studies are required to validate and evaluate current findings in the context of response and side-effect development. This may ultimately lead to molecular tests that can aid in the selection of antipsychotic treatments.     

Management of atypical antipsychotic-induced weight gain in schizophrenic patients with topiramate

Patients treated with atypical antipsychotic drugs commonly gain excess weight. Because obesity is associated with considerable morbidity and decreased life expectancy, treatment of weight gain in these patients is critical. Topiramate, a fairly new anticonvulsant, promotes bodyweight loss in healthy obese subjects, patients with bipolar disorder, and patients with eating disorder. However, there are very few reports about the efficacy of topiramate for weight management in schizophrenic patients. We present the cases of three Taiwanese patients with schizophrenia whose bodyweight increased as a result of atypical antipsychotics treatment, then was controlled by topiramate without aggravation of their psychotic symptoms.     

SNAP-25 gene polymorphisms and weight gain in schizophrenic patients

Drug induced weight gain is a serious side effect of several atypical antipsychotics. As genetic factors play an important role in the homeostasis of hunger/satiety we tried to replicate a preliminary previous finding about an impact of three polymorphisms in the synaptosomal-associated protein of 25kDa (SNAP-25; sites MnlI, TaiI and DdelI in the 3(')-UTR) on clinical response and antipsychotic induced weight gain. We genotyped 162 schizophrenic patients being treated in monotherapy with atypical antipsychotics and 312 healthy control subjects for the three polymorphisms in the SNAP-25 gene using PCR. PANSS scores and weight were measured weekly for a minimum of five weeks. We found significant associations between the TaiI and MnlI polymorphisms and serum triglyceride levels at baseline and for the DdelI polymorphism and weight gain. In conclusion our study can at least partly replicate the previous findings concerning the impact of SNAP-25 gene polymorphisms on weight gain during antipsychotic treatment.     

抗精神病药对精神分裂症患者体重的影响

目的 为了探讨抗精神病药对精神分裂症患者体重的影响。方法 295例服用抗精神病药的精神分裂症患者进行了临床调查。结果 67．12％患者出现体重增加；体重增加从多到少的药物依次是氯氮平、奥氮平、氯氮平合并利培酮、氯丙嗪、利培酮、氯氮平合并舒必利；氯氮平、氯丙嗪、利培酮体重增加较人组前有显著差异；女性患者、初次服抗精神病药者、合并心境稳定剂者体重增加亦明显。结论 大部分抗精神病药可导致体重增加，应在治疗前及治疗中定期进行体重监测。     

Effectiveness of a structured diet program in antipsychotic-induced weight gain in patients with schizophrenia

Objective.The aim of this study was to evaluate the effectiveness of a structured diet program in weight loss in patients with schizophrenia. Methods. A total of 38 outpatients diagnosed with schizophrenia according to DSM-IV and who had complaints of weight gain during treatment with various antipsychotic drugs were invited to participate in a 3-month structured diet program. Thirty-two patients and another 40 patients were included as the control group. At the beginning of the diet program, the patients were given a form in order to evaluate their eating habits, and blood samples were taken to measure plasma lipid profile, and fasting blood glucose (FBG) level. Patients’ baseline weight, body mass index (BMI), and basal metabolism rate (BMR) were recorded. Results. Thirty-two patients with schizophrenia, who attended a 3-month structured diet program had mean weight loss of 6.19 kg, whereas patients in the control group gained 1.6 kg. Conclusion. Our findings show that a diet program is effective in managing antipsychotic-induced weight gain. The degree of weight loss seems to be correlated with the duration in which the patient is on the diet program. However; younger patients had less benefit from the diet program.     

The influence of 5-HT(2C) and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic patients

We investigated the relationships between functional genetic variants of the 5-HT(2C) receptor and multidrug-resistant protein (MDR1), coding for P-glycoprotein, and second generation antipsychotic (SDA)-induced weight gain among 108 female schizophrenic patients treated with olanzapine or risperidone for up to 4 months. No significant differences in -759C/T allelic and genotype variants of 5-HT(2C) were found between patients who gained more than 7% of their initial weight compared with those who gained less. Haplotype-based analysis of two MDR1 loci, exon 21 G2677T and exon 26 C3435T, revealed a slightly lower representation of the G2677/C3435 haplotype in the >/=7% group. In the subgroup of patients treated with risperidone, we found borderline overrepresentation of 2677T, significant overrepresentation of 3435T variant and borderline overrepresentation of 2677T/3435T haplotype the >/=7% group, whereas G2677/C3435 haplotype was found to be less represented in the >/=7% group. Our data indicate a nonsignificant role of 759C/T 5-HT(2C) in SDA-induced weight gain, and a stronger influence of the MDR1 G2677T and C3435T polymorphisms on risperidone-induced weight gain in female schizophrenic patients. 3435T and 2677T MDR1 variants, both associated with lower P-gp function, might predispose to higher risperidone accessibility to the brain that would lead to stronger effects, including weight gain.     

首发精神分裂症患者利培酮治疗前后的记忆功能研究

目的　研究首发精神分裂症患者记忆损害特点及其治疗。方法　 30例符合ICD 10精神分裂症诊断标准的首发患者入组 ,用利培酮治疗 (3 87± 0 95 )mg d 8周后分别用Wechsler记忆量表(WMS)测定患者的记忆功能 ,阳性及阴性症状量表 (PANSS)及治疗中需处理的不良反应症状量表(TESS)评价患者精神症状及不良反应的严重程度。结果　经配对t检验 ,精神分裂症患者的记忆商数 (MQ)及其大部分分测验 (10 0至 1例背数字、视觉再认测验、联想学习测验、触觉测验、理解记忆测验及数字广度测验 )治疗前后的差异具有统计学意义 (P <0 0 5或 0 0 1)。治疗前后MQ的差值与PANSS总分差值及阳性总分差值具有显著相关性 (r分别为 0 5 0 1及 0 6 0 6 )。结论　 (1)首发精神分裂症患者在发病初期就存在记忆损害。 (2 )利培酮对精神分裂症的记忆损害具有治疗作用 ,记忆功能的改善与精神症状 (阳性症状 )的好转具有显著相关性     

Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics

Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n = 57), risperidone (n = 23) or typical antipsychotics (n = 44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.     

Subcortical modulation of attentional control by second-generation antipsychotics in first-episode psychosis

Psychotic disorders are characterized by significant deficits in attentional control, but the neurobiological mechanisms underlying these deficits early in the course of illness prior to extensive pharmacotherapy are not well understood. Moreover, little is known regarding the symptom and brain changes associated with amelioration of attentional impairments through antipsychotic pharmacotherapy. In this study 14 male patients experiencing a first-episode of psychosis with minimal prior antipsychotic treatment completed an attentional control task while undergoing functional magnetic resonance imaging at the onset of treatment with a second generation antipsychotic (risperidone or aripiprazole) in a double blind randomized clinical trial and then again following approximately 12 weeks of treatment. In addition, 14 age-, and performance-matched healthy male volunteers who were not treated completed the same task at a baseline timepoint and then again following 12 weeks. Patients showed significantly greater activation than healthy volunteers in the right globus pallidus, left thalamus, and right thalamus at the time of the baseline scan. Among patients there was a significant reduction in right globus pallidus blood-oxygen level dependent (BOLD) response following antipsychotic treatment that correlated significantly with improvement in response accuracy and reductions in thought disturbance. No changes in globus pallidus activation were observed in healthy volunteers over this time period. These preliminary findings suggest that improvement in attentional control and concomitant reductions in thought disturbance in first-episode psychosis may be associated with reductions in subcortical activity following administration of second-generation antipsychotics early in the course of illness. These findings have implications for understanding how changes in basal ganglia activity may be linked to improvements in attentional control through antipsychotics.     

奥氮平对首发精神分裂症患者的疗效及认知功能影响

目的观察奥氮平对首发精神分裂症患者的疗效及认知功能的影响。方法对31例首发精神分裂症患者在奥氮平治疗前及治疗12周后,用阳性症状量表（SAPS）、阴性症状量表（SANS）、韦氏成人智力量表（WAIS—R）、韦氏记忆量表（WMS）、简明精神病评定量表（BPRS）、韦斯康星卡片分类测验（WCST）进行评估,并观察奥氮平对精神分裂症症状的疗效及对认知功能的影响。结果治疗后SAPS、SANS、BPRS〈WCST中错误应答数的评估分值显著降低（P〈0．01）,且非持续性错误、WMS的再生、理解评估分值也明显降低（P〈0．05）。结论奥氮平治疗精神分裂症疗效可靠并可显著改善部分患者的认知功能。