抗精神病药物与肝损害的研究进展

在精神科临床用药过程中,肝功能异常的发生十分常见。有共识的容易产生肝损害的抗精神病药物有氯丙嗪、多虑平等。出现肝损害时,临床医师往往采取保肝治疗、减药、换药治疗等方式。目前临床上使用的抗精神病药物品种繁多,其中非典型抗精神病药物得到了较普遍的使用,并逐渐取代了典型抗精神病药物的地位。     

抗精神病药物对乙肝病毒感染患者肝功能影响的对照研究

目的许多研究认为抗精神病药物可导致肝损害，但还不清楚服用抗精神病药物的同时乙肝病毒感染对肝功能的影响，及抗精神病药物是否会加重肝损害。方法本文对照研究了抗精神病药物对乙肝病毒感染（ＨＢＶ）、未感染和曾感染但已恢复的精神分裂症患者肝功能的影响。结果我们发现三组肝功能异常发生率（１９％、２３％和２０％）无显著性差异，抗精神病药物所致肝损害与是否存在乙肝病毒感染无关。结论抗精神病药物所致肝损害除变态反应外可能还有直接细胞毒效应，抗精神病药物与乙肝病毒对肝功能的损害并无叠加作用     

抗精神药物对乙肝病毒感染患者肝功能影响的对照研究

目的 许多研究认为抗精神病药物可导致肝损害，但还不清楚服用抗精神病药物的同时乙肝病毒感染对肝功能的影响，及抗精神病药物是否会加重肝损害。方法 本文对照研究了抗精神病药物对乙肝病毒感染（ＨＢＶ）、未感染和曾感染但已恢复的精神分裂症患者肝功能的影响。结果 我们发现三组肝功能异常发生率（１９％、２３％和２０％）无显著性差异，抗精神病药物所致肝损害与是否存在乙肝病毒感染无关。结论 抗精神病药物所致肝损害除     

2006年我国十省市抗精神病药联合用药情况调查及其影响因素分析

目的 调查2006年我国10个省市精神分裂症患者抗精神病药联合用药的现状,并初步研究其影响因素.方法 按人均国民生产总值,将各省分为5个经济发展等级,以一定的抽样比例,选择10个省市的41所精神病专科医院或综合医院精神科的5898例精神分裂症住院患者和门诊患者,于2006年5月22-28日使用自制调查问卷进行抗精神病药治疗现况调查.结果 (1)4306例(73.0％)患者单独使用1种抗精神病药,其中74例(1.2％)单独使用长效抗精神病药,1237例(21.0％)患者单独使用第1代抗精神病药,2995例(50.8％)患者单独使用第2代抗精神病药,1541例(26.1％)患者联合使用≥2种抗精神病药.联合用药患者中,291例(4.9％)联用长效抗精神病药与非长效抗精神病药,1250例(21.2％)联用≥2种非长效抗精神病药,其中159例(2.7％)联用≥2种第1代非长效抗精神病药,741例(12.6％)联用第1代与第2代抗精神病药,350例(5.9％)联用≥2种第2代抗精神病药.(2)联合用药组震颤、静坐不能、嗜睡、便秘、流涎、口干、体位性低血压、体质量改变、肝功能变化等不良反应的发生比例显著高于单一用药组(P＜0.05).(3)Logistic回归分析结果显示,门诊或住院治疗、所在地区、年龄、病程(总病程和本次病程)、就诊次数、阴性症状、情感症状、思维奔逸、言语活动增多、攻击以及疾病的严重程度可能为使用联合用药方式的影响因素(P＜0.01).结论 当前我国精神分裂症患者使用抗精神病药以单一用药为主,联合用药方式发生不良反应的风险更高,应当掌握联合用药的适应证;联合用药方式受到多种因素的影响.     

托吡酯与二甲双胍治疗抗精神病药致肥胖的疗效的对照研究

目的:探讨托吡酯与二甲双胍治疗抗精神病药致肥胖的作用及安全性.方法:随机将62例抗精神病药致肥胖、且病情稳定的精神分裂症患者分为托吡酯组及二甲双胍组;在原抗精神病药种类、剂量治疗的基础上分别给予托吡酯及二甲双胍.分别于干预前、干预后进行阳性和阴性症状量表(PANSS)评估,测量体质量、体质量指数(BMI)、腰臀比(WH...     

抗精神病药致肝损害的研究进展

药物性肝损害是抗精神病药治疗过程中常见的不良反应,也是精神病人停止治疗的常见原因之一,本文简要综述近年来抗精神病药致肝损害的研究进展。     

抗精神病药致肠梗阻53例临床分析

目的:对抗精神病药致肠梗阻的临床特点进行分析.方法:对53例精神疾病患者在药物治疗过程中合并肠梗阻的临床表现、腹部X线检查及预后进行比较.结果:53例患者中,以40岁以上、服用抗精神病药5年以上及服用氯氮平(45.2%)后发生肠梗阻较为多见;临床表现均有渐进式腹胀、肠鸣音减弱或肠鸣音消失;腹部X线检查均可见肠管扩张及液平面;经治疗后49例痊愈,4例死亡.结论:各类抗精神病药均可引起肠梗阻,腹部X线检查有助于早期确诊.     

长期使用抗精神病药患者血清游离脂肪酸水平与有关因素研究

目的:探讨长期(1年以上)使用抗精神病药患者的血清游离脂肪酸(FFAs)水平,及其与空腹血糖和胰岛素抵抗之间的关系. 方法:调查308例长期使用抗精神病药住院患者,用比色法检测患者空腹血清FFAs,用放射免疫法测定患者血清胰岛素和瘦素. 结果:与长期使用抗精神病药有关的体质量(体重)增加或肥胖、糖耐量降低和糖尿病患者的血清FFAs水平显著高于对照组(P值分别为0.04, 0.01和0.022),且与空腹血糖、胰岛素抵抗均呈显著正相关(P值分别为0.005和0.04). 结论:长期使用抗精神病药的精神分裂症患者的高血清FFAs水平影响患者的糖代谢,并参与胰岛素抵抗乃至糖尿病的发生,是代谢紊乱综合征的重要特征之一.     

癫(癎)性精神障碍患者临床用药调查

目的:了解癫性精神障碍患者临床药物使用情况。方法:对89例癫性精神障碍患者使用抗癫药和抗精神病药情况进行分析。结果:在癫性精神障碍治疗中,抗癫药以卡马西平使用频度最高达65.2%,抗癫药不良反应发生率为15.7%,抗精神病药不良反应以锥体外系反应居首位。结论:在癫性精神障碍治疗中,应合理使用抗癫药与抗精神病药。     

2006年我国十省市抗精神病药处方方式的现况调查

目的 调查2006年我国10省市抗精神病药处方方式;分析4年间我国抗精神病药处方方式的变化趋势.方法 按照作者2002年的调查方法,选择10省市41所精神疾病专科医院或综合医院精神科的5898例精神分裂症门诊和住院患者,于2006年5月22-28日使用自制修订的调查问卷进行精神分裂症处方方式的现况调查.结果 (1)5898例患者中,门诊患者为2716例(46.0%);住院患者为3182例(54.0%);男3041例(51.6%),女2803例(47.5%),缺失54例数据.(2)99.1%的患者接受了抗精神病药治疗,使用频率在前7位的药物依次为:氯氮平(31.7%),利培酮(30.5%),舒必利(14.5%),氯丙嗪(10.8%),奋乃静(9.2%)、喹硫平(7.2%),氟哌啶醇(5.8%).换算为氯丙嗪等效剂量后,住院患者平均药物剂量显著高于门诊患者.(3)72.7%的患者使用第2代抗精神病药治疗;第1代抗精神病药的使用频率为38.3%;6.19%的患者接受了长效药物治疗.(4)75.6%的患者接受了单一非长效抗精神病药治疗;24.4%的患者联合使用2种或2种以上抗精神病药.(5)54.1%的患者联合了抗胆碱能药、苯二氮革类、β-受体阻断剂、抗抑郁药和心境稳定剂,主要用于控制不良反应或增效治疗.结论 第2代抗精神病药已经成为我国治疗精神分裂症的主流药物,反映出精神分裂症治疗理念和治疗技术的进展.     

Effects of typical, atypical, and no antipsychotic drugs on visual contrast detection in schizophrenia

OBJECTIVE: Visual contrast detection has been reported in some studies to be normal in schizophrenia patients, but in other studies impairments have been reported. Because contrast detection in the visual processing system is mediated by dopamine, and because the pharmacotherapy of schizophrenia involves blocking dopamine postsynaptic receptor sites, the authors investigated the effects of dopamine-blocking antipsychotic drugs on visual contrast detection in schizophrenia. METHOD: Visual contrast detection thresholds were measured in healthy subjects and schizophrenia patients receiving typical and atypical antipsychotic drugs; a two-alternative, forced-choice psychophysical method was used. Also included were six patients receiving no antipsychotic treatment as well as clinically unaffected first-degree relatives of the schizophrenia patients. RESULTS: Patients receiving atypical antipsychotic drugs showed unimpaired visual contrast detection, those given typical antipsychotic drugs exhibited higher visual contrast detection thresholds, and the unmedicated schizophrenic patients showed visual contrast detection thresholds significantly below those of healthy subjects. CONCLUSIONS: Dopamine modulation via D(2) receptor blockade affects sensory processes in schizophrenia, shifting visual contrast detection from hypersensitivity in the unmedicated state to normal and even to hyposensitive levels. Thus, antipsychotic drug treatment may account for the inconsistent reports concerning visual contrast detection in schizophrenia.     

自由基代谢与精神分裂症临床症状和药物治疗的关系

目的：探讨自由基代谢与精神分裂症临床症状和药物治疗的关系。方法：是否治疗的慢性精神分裂症患者各４０例分别评定定阳性和阴性症状量表（ＰＡＮＳＳ）,并测定膜脂质过氧化物丙二醛（ＭＤＡ）含量、铜／锌超氧化物歧化酶（Ｇｕ－ＺｎＳＯＤ）和谷胱苷肽过氧化物酶（ＧＳＨ－Ｐｘ）活性。结果：与健康对照组相比,未治疗组患者ＭＤＡ含量和ＧＳＨ－Ｐｘ活性显著增加,治疗组患者无显著改变;而两组患者ＳＯＤ活性显著降低;未治疗     

Influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia: comparison of middle-aged and older adults.

OBJECTIVE: The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia. METHODS: Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology. RESULTS: The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline. CONCLUSION: These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.     

Correlation between plasma homovanillic acid levels and the response to atypical antipsychotics in male patients with schizophrenia

OBJECTIVE: The authors investigated the effects of atypical antipsychotic drugs-olanzapine, perospirone, and quetiapine-on plasma homovanillic acid (pHVA) in male patients with chronic schizophrenia. METHODS: In this prospective, open-label study, the subjects were 30 inpatients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia. The authors switched patients from typical antipsychotic drugs to olanzapine, perospirone, or quetiapine. Each patient gave informed consent for the research. pHVA was assessed before and after switching medications. RESULTS: After the switch, the authors found a significant improvement in psychotic symptoms, nonsignificant improvement in extrapyramidal symptoms, and a nonsignificant reduction in pHVA. In addition, the baseline pHVA correlated positively with the score changes from baseline in the Brief Psychiatric Rating Scale (BPRS) total, positive, and negative symptoms in the group with a whole sample and in the olanzapine-treated group, and with the score changes in the BPRS total and positive symptoms in the quetiapine-treated group. CONCLUSION: Our findings indicated that the preswitching pHVA levels could be used to predict changes in the psychotic symptoms of male patients with chronic schizophrenia when switching to atypical antipsychotic drugs.     

Chronic nicotine interactions with clozapine and risperidone and attentional function in rats

Although antipsychotic drugs are therapeutically effective in attenuating the hallmark symptoms of schizophrenia, these improvements do not return most patients to normative standards of cognitive function. Thus, complementary drug treatment may be needed to treat the attentional deficits of schizophrenia as well as to counteract the potential attentional impairments caused by some antipsychotic drugs. Nicotine, a drug commonly self-administered by a great majority of individuals with schizophrenia, has been shown to significantly improve cognitive function in some studies. The current study was conducted to determine the interactive effects of the atypical antipsychotic drugs clozapine and risperidone with chronic nicotine administration on attentional performance. Adult female Sprague-Dawley rats (N=35) were trained to perform an attentional task using an operant visual signal detection task. After training, rats were infused with a dose of 5 mg/kg/day (s.c.) nicotine base (n=18) or saline (n=17) for 28 consecutive days via osmotic pump. In Exp. 1, while being administered chronic nicotine or saline, rats were given acute doses of clozapine (0, 0.625, 1.25 and 2.5 mg/kg, s.c.) and were tested for attentional function. In Exp. 2, while on chronic nicotine or saline, other rats were challenged with acute doses of risperidone (0, 0.025, 0.05 and 0.1 mg/kg, s.c.) and were tested for attentional function. Results showed that acute administration of clozapine caused a significant dose-dependent impairment in choice accuracy (percent hit) in animals treated with chronic saline. Chronic nicotine treatment itself lowered accuracy, but attenuated further declines with acute clozapine treatment. Acute administration of risperidone at high dose significantly reduced performance (percent correct rejection) in chronically saline-treated rats, but in a similar fashion as in Exp. 1, chronic nicotine lowered accuracy but attenuated further impairment with acute risperidone. In summary, atypical antipsychotic drugs clozapine and risperidone significantly impaired choice accuracy in the visual signal detection task. Clozapine was more detrimental than risperidone but the adverse effects of both clozapine and risperidone on attentional performance were masked in rats chronically treated with nicotine.     

Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population

OBJECTIVE: To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia. METHOD: Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive 1 of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS. CONCLUSION: These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.     

Effectiveness of olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia after discontinuing perphenazine: a CATIE study

OBJECTIVE: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient's previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic perphenazine. METHOD: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5-30.0 mg/day (N=38); quetiapine, 200-800 mg/day (N=38); or risperidone, 1.5-6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment discontinuation and measures of drug tolerability. RESULTS: The time to treatment discontinuation was longer for patients treated with quetiapine (median, 9.9 months) and olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision. CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued the older antipsychotic perphenazine, quetiapine and olanzapine were more effective than risperidone, as reflected by longer time to discontinuation for any reason. In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances.     

Potentiation of the NMDA receptor in the treatment of schizophrenia: focused on the glycine site

N-methyl-D-aspartate receptor (NMDAR) hypo-function theory of schizophrenia proposes that impairment in NMDAR function be associated with the pathophysiology of schizophrenia and suggests that enhancement of the receptor function may produce efficacy for schizophrenia. Consistent with this theory, for the last decade, clinical trials have demonstrated that the enhancement of NMDAR function by potentiating the glycine site of the receptor is efficacious in the treatment of schizophrenia. Full agonists of the glycine site, glycine and D-serine and a glycine transporter-1 inhibitor, sarcosine, added to antipsychotic drugs, have been shown to be effective in the treatment of negative symptoms and possibly cognitive symptoms without significantly affecting the positive symptoms of schizophrenia. A partial agonist of the glycine site, D-cycloserine, added to antipsychotic drugs, can be effective for the negative symptoms at the therapeutic doses. However, these drugs have not shown clinical efficacy when added to clozapine, suggesting that the interactions of clozapine and the glycine site potentiators may be different from those of other antipsychotic drugs and the potentiators. This article suggests that the glycine site potentiators may produce efficacy for negative and cognitive symptoms by blocking apoptosis-like neuropathological processes in patients with chronic schizophrenia and thereby can deter progressive deterioration of the disorder. This article proposes a polypharmacy of glycine site potentiators augmented with antipsychotic drugs to control positive and negative symptoms in a synergistic manner and block deterioration in schizophrenia. Since the NMDAR complex consists of multiple sites modulating receptor functions, the efficacy of glycine site potentiators for schizophrenia suggests the possibility that manipulation of other modulating sites of the NMDAR can also be efficacious in the treatment of schizophrenia.     

Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study

This study aimed to determine the effect of olanzapine and other antipsychotic drugs on cognitive functions after 6months of treatment. Baseline, 3month and 6month psychopathological and cognitive evaluations were made. Thirty-eight partially responsive outpatients with DSM-IV chronic schizophrenia diagnosis were included in the study. On the indication of their attending psychiatrists, 21 patients initiated treatment with olanzapine, and 17 remained on their previous treatment with other antipsychotic drugs. Cognitive assessments were blind to medication and psychopathological status.The olanzapine group presented a significantly greater improvement in negative symptomatology and verbal memory than the comparison group in repeated-measures of MANOVAs between baseline, 3month and 6month assessments. These differences remained statistically significant after covarying out gender, treatment with other atypical antipsychotics, biperidene doses and changes in positive and negative symptoms. In order to match previous differences between groups, cognitive baseline scores for each test were introduced as covariates, resulting in a significant improvement for the olanzapine group in negative symptomatology and the interference task of the Stroop test.We then re-analyzed the data, dividing the comparison group into two groups: risperidone-treated patients (n=9) and patients receiving conventional antipsychotic drugs (n=8). Post-hoc analyses between groups were carried out with baseline cognitive assessment as covariate. The olanzapine group improved significantly more than the risperidone group in negative symptomatology and in the interference task of Stroop test. The improvement in the number of categories of the Wisconsin Card Sorting Test was higher in risperidone patients than in those receiving olanzapine or conventional antipsychotic treatment. Conventional antipsychotic drugs did not present a significant improvement over atypical antipsychotic drugs in any cognitive function.In summary, in patients suffering from chronic schizophrenia, atypical antipsychotic agents were associated with slight differential improvements over time in attentional, verbal memory and executive functions compared with conventional neuroleptic drugs. No differential improvements were found in social functioning, verbal fluency, non-verbal domains of memory or visuo-motor abilities.     

Potentiation of the NMDA receptor in the treatment of schizophrenia: focused on the glycine site

N-methyl-d-aspartate receptor (NMDAR) hypo-function theory of schizophrenia proposes that impairment in NMDAR function be associated with the pathophysiology of schizophrenia and suggests that enhancement of the receptor function may produce efficacy for schizophrenia. Consistent with this theory, for the last decade, clinical trials have demonstrated that the enhancement of NMDAR function by potentiating the glycine site of the receptor is efficacious in the treatment of schizophrenia. Full agonists of the glycine site, glycine and d-serine and a glycine transporter-1 inhibitor, sarcosine, added to antipsychotic drugs, have been shown to be effective in the treatment of negative symptoms and possibly cognitive symptoms without significantly affecting the positive symptoms of schizophrenia. A partial agonist of the glycine site, d-cycloserine, added to antipsychotic drugs, can be effective for the negative symptoms at the therapeutic doses. However, these drugs have not shown clinical efficacy when added to clozapine, suggesting that the interactions of clozapine and the glycine site potentiators may be different from those of other antipsychotic drugs and the potentiators. This article suggests that the glycine site potentiators may produce efficacy for negative and cognitive symptoms by blocking apoptosis-like neuropathological processes in patients with chronic schizophrenia and thereby can deter progressive deterioration of the disorder. This article proposes a polypharmacy of glycine site potentiators augmented with antipsychotic drugs to control positive and negative symptoms in a synergistic manner and block deterioration in schizophrenia. Since the NMDAR complex consists of multiple sites modulating receptor functions, the efficacy of glycine site potentiators for schizophrenia suggests the possibility that manipulation of other modulating sites of the NMDAR can also be efficacious in the treatment of schizophrenia.