氯氮平致药源性强迫症状的调查

目的：了解在应用抗精神病药物治疗精神分裂症过程中出现的强迫症状,是否为药物所致。方法：对上海市精神卫生中心分部某一病区所有正在应用抗精神病药物治疗的住院精神分裂症病人,以Y－BOCS及MSCPOR量表评定,凡发现有强迫症状,予以减药直至停药,观察强迫症状的变化,以期证其与抗精神病药物的关系。结果：共调查430名,发现确实系抗精神病药物所强迫症状者4例,均为服用氯氮平者,占服氯氮平病例总数,发现确实系抗精神病药所致强迫症状者4例,均为服用氯氮平者,占服氯氮平病例总数1．41％。结论氯凿可产生强迫症状,在临床应用时应予注意。     

氯氮平与强迫症状——读者来信(一)

编辑先生：众所周知,精神分裂症可伴有强迫症状,并有报告认为,氯氮平可引起强迫症状,若以氯氮平治疗精神分裂症,原无强迫症状,而在疾病缓解时出现,则应如何诊断和处理？请赐复。安徽阜阳市精神病院　宁南义答读者来信（一）宁南义医师：一般说来,一个原无强迫症状和精神分裂症患者经氯氮平治疗病情缓解时出现强迫症状,可以考虑强迫症状系氯氮平所致。如果想肯定诊断,可采用换药—再用药的方法予以证实。这一方法是：将氯氮平换成其它抗精神病药治疗一段时间,如强迫症状消失,则可能性极大;当再次换成氯氮平治疗时,强迫症状又出…     

三种不同情况强迫症状的临床特点及全血5-羟色胺浓度的比较研究

目的比较强迫症、精神分裂症伴有的强迫症状和精神分裂症经氯氮平治疗导致的强迫症状等3组不同患者在症状学和全血5-羟色胺(5-HT)浓度方面的差异,探讨强迫症状与5-HT异常间的关系。方法对强迫症、伴强迫症状的及氯氮平治疗导致强迫症状的精神分裂症各15例,不伴强迫症状的(19例)以及氯氮平治疗未导致强迫症状的精神分裂症组(15例)使用Yale-Brown强迫量表(YBOCS)、汉密顿焦虑量表(HAMA)、汉密顿抑郁量表(HAMD)及阳性和阴性症状量表(PANSS)进行临床症状评定;采用高效液相色谱法检测上述5组和正常组(15例)的全血5-HT浓度。结果强迫症和精神分裂症伴有的强迫症状中强迫思维和行为均多见,而氯氮平导致的强迫症状则以强迫行为为主。有无强迫症状的精神分裂症组比较,后者的PANSS阳性量表分低,HAMA评分高(P<0.05)。有强迫症状的3组患者的全血5-HT浓度均低于无强迫症状的3组(正常组,精神分裂症不伴强迫症状组和氯氮平治疗未导致强迫症状组)(P<0.05),并且全血5-HT浓度和这3组的YBOCS分,强迫思维评分及强迫行为评分均无显著相关性。结论强迫症状在强迫症和精神分裂症中存在着症状学差异;5-HT功能低下可能是这三种强迫症状产生的共同生化机制之一。     

药源性迟发性强迫状态与精神分裂症强迫症状的比较

药源性迟发性强迫状态与精神分裂症强迫症状的比较韩春美韩勇冯永平抗精神病药治疗精神病过程出现的副反应多种多样，但表现为各种神经症者易被忽视，如药源性强迫状态，尤其是迟发性强迫状态，至今国内外报道尚少。现将所见４０例药源性迟发性强迫状态与精神分裂症强迫症...     

不同精神障碍中的强迫症状

强迫症状是以反复出现的强迫观念和强迫动作为基本特征的一种常见而难治的精神症状。人们已经认识到该症状并非强迫性神经症所特有 ,在精神分裂症和抑郁症中强迫症状都占有相当比例 ;而且 ,抗精神病药物尤其是非典型抗精神病药物能引起或加重强迫症状 ,称为药源性强迫症。本文复习了近年来的文献 ,对此三种情况中的强迫症状与强迫性神经症进行临床比较分析 ,并探讨其发生机制。1　临床特点1 1　精神分裂症与强迫症状　不同文献报道强迫症状在精神分裂症中的发生率相差甚远。国外的报道为 1.1%～ 4 6 %不等 ,国内则在 1.7%～ 2 3%之间。各家…     

精神分裂症患者的强迫症状

强迫症状是精神分裂症常见症状之一 ,也是药物治疗中常见的副反应 ,其发生率多报告在 14 %～2 5 %之间 ,也有报道为 3 5 % (回顾性方法 )或 4 6 % ,可能与不同研究人员使用不同检测工具、方法及对症状认识不同有关。Ｐｏｙｕｒｏｖｓｋｙ等[1] 发现 ,首发精神分裂症患者有 14 %伴强迫症状。Ｔｉｂｂｏ等[2 ] 发现 ,2 5 %的精神分裂症患者有强迫症状 ,用氯氮平治疗时 ,超过 10 %的患者出现强迫症状。1　机制探讨作者单位 :5 180 2 0　深圳市康宁医院体内 5 羟色胺 (5 ＨＴ)系统与多巴胺 (ＤＡ)系统有相互抑制作用 ,而非典型抗精神病药对 5 …     

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。     

强迫症与精神分裂症

强迫症状常出现在强迫症,但也可见于其他精神疾病,如精神分裂症、抑郁症、器质性疾病等,也可由于多种抗精神病药引起,造成临床鉴别困难的病例十分常见。近些年来,由于精神疾病临床症状的多样化、轻性化和不典型化,特别在疾病早期,似乎有分裂症可疑,但又有强迫症状、抑郁症状或疑病症状,究竟应该诊断为精神分裂症呢,还是强迫症、情感性精神障碍或疑病症,作者经常为这些精神疾病的鉴别诊断     

氯氮平所致静坐不能的发生率及严重程度

氯氮平属弱多巴胺拮抗剂,因锥体外系反应轻,抗精神病作用谱广,引起了研究者的极大兴趣。1987年Claghorn报告氯氮平所致的巴金森综合征仅是氯丙嗪的1/3,但两者所致静坐不能基本相同,鉴于氯氮平所致静坐不能的研究为数不多,本文选择了氯氮平及经典抗精神病药治疗的两组病人进行盲性研究。方法:选择23例服用氯氮平的病人及29例服用经典抗精神病药病人。所有病人均因精神障碍接受治疗。服经典抗精神病药病人     

精神分裂症伴强迫症状的临床研究

目的 分析伴强迫症状的精神分裂症临床特点及治疗效果，为临床诊断及治疗提供参考。方法 对伴强迫症状的精神分裂症与不伴强迫症状的精神分裂症各38例进行对照分析，使用维思通抗精神病药物治疗，采用阳性及阴性症状量表（PANSS）、强迫症状量表（Y—BOCS）、Hamilton抑郁量表（HAMD）、Hamilton焦虑量表（HAMA）评定疗效。结果 伴强迫症状的精神分裂症起痛年龄早，起病隐袭，病程迁延，以阴性症状为主，住院时间长，治疗效果差，Y—BOCS、HAMD、HAMA等量表评分明显高于不伴强迫症状的精神分裂症，有显著性差异。结论 伴强迫症状的精神分裂症，具有一定的异质性，单一使用抗精神病药物疗效差。     

Antipsychotics and obsessive–compulsive disorder/obsessive–compulsive symptoms: A pharmacovigilance study of the FDA adverse event reporting system

Objective

Antipsychotics have conflicting data with respect to obsessive–compulsive disorder/symptoms (OCD/OCS), with some reporting causality and some reporting treatment benefits. This pharmacovigilance study aimed to investigate reporting of OCD/OCS in association with the use of antipsychotics in comparison to one another, as well as treatment failure using data derived from the FDA Adverse Event Reporting System (FAERS).

Methods

Data from January 1st, 2010 to December 31st, 2020 on suspected adverse drug reactions (ADRs) including OCD/OCS was obtained. The information component (IC) was used to determine a disproportionality signal, and reporting odds ratio (ROR) calculations were performed via intra-class analyses to discern differences between the evaluated antipsychotics.

Results

A total of 1454 OCD/OCS cases were utilized in IC and ROR calculations and 385,972 suspected ADRs were used as non-cases. A significant disproportionality signal was seen with all second generation antipsychotics. Relative to other antipsychotics, only aripiprazole had a significant ROR of 23.87 (95% CI: 21.01–27.13; p < 0.0001). The ROR for antipsychotic treatment failure in those with OCD/OCS was highest with aripiprazole, and lowest with risperidone and quetiapine. Sensitivity analyses were largely in favor of the primary findings. Our analysis appears to implicate the 5-HT_1A receptor or an imbalance between this receptor and the D₂-receptor in antipsychotic treatment-emergent OCD/OCS.

Conclusions

In contrast to prior reports noting clozapine as the antipsychotic most commonly associated with de novo or exacerbated OCD/OCS, this pharmacovigilance study found aripiprazole was most frequently reported for this adverse effect. While these findings from FAERS offer a unique perspective on OCD/OCS with different antipsychotic agents, due to the inherent limitations of pharmacovigilance studies they should ideally be validated through alternative prospective research studies involving direct comparisons of antipsychotic agents.     

Treatment of generalized tardive dystonia with clozapine

Tardive dystonia is a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures, associated with prolonged exposure to antipsychotics. We report a case of a 35-year-old patient with schizophrenia who developed a generalized form of tardive dystonia after switching of clozapine to risperidone treatment that persisted after switch to olanzapine and during the period while treatment with an antipsychotic was discontinued. It was successfully managed with reintroduction of clozapine. The case may represent the first report of generalized tardive dystonia while taking risperidone. The possible pathophysiological bases of the disorder are discussed. The goal of our report is to emphasize that an adequate trial of clozapine is a worthwhile option in the cases of tardive dystonia, even where discontinuation of antipsychotics was unsuccesful.     

Aripiprazole improves olanzapine-associated obsessive compulsive symptoms in schizophrenia

Many schizophrenic patients have comorbid obsessive-compulsive syndromes (OCS) frequently associated with antiserotonergic second-generation antipsychotics such as clozapine and olanzapine. Whereas cognitive behavioral therapy and antiobsessive antidepressants brought up inconsistent results, pharmacological add-on strategies were able to alleviate OCS. One suggestive agent for antiobsessive add-on treatment is aripiprazole, a partial agonist at dopamine and serotonin receptors. Here, we summarize the course of a patient with paranoid schizophrenia. She developed OCS during long-term treatment with olanzapine at 20 mg/d over a period of 10 years. Baseline assessment showed severe obsessions (Yale Brown Obsessive Compulsive Scale (YBOCS) subscale score : 13) and compulsions (YBOCS subscale score : 10), whereas the psychotic syndrome was compensated (Positive and Negative Syndrome Scale, 11/17/28). The combination with aripiprazole (15 mg/) over a period of 12 weeks resulted in a marked improvement of OCS (YBOCS, 8/3) and some further improvement of the psychotic symptoms (Positive and Negative Syndrome Scale, 9/13/27). This observation points toward an antiobsessive potency of aripiprazole in combination with olanzapine, quite similar to approaches involving clozapine. Hence, the proposed strategy should be further evaluated in prospective controlled trials.     

Schizophrenic with obsessive-compulsive disorder or symptoms

The concept of pseudo-obsessive schizophrenia has been often used in the past. Clinically, severe obsessive-compulsive disorders (OCD) are closed from psychotic symptoms and ask questions about differential diagnosis with schizophrenia. Moreover some characterized schizophrenia may present in some cases obsessive compulsive symptoms (OCS). Finally, schizophrenia treated by atypical antipsychotics can be complicated by obsessive compulsive symptoms following the onset of the drug. Until now, there have been no control trials on this specific topic. Reviewing data of studies exploring the prevalence of OCD in schizophrenia this current article summarizes the different pharmaceutical approaches used in treating this disorder. In addition, a review about antipsychotics causing either emergence or exacerbation of OCS is presented.     

Combination of clozapine and amisulpride in treatment-resistant schizophrenia--case reports and review of the literature

BACKGROUND: The clinical outcome of patients suffering from schizophrenic psychoses has been considerably improved by atypical antipsychotics like clozapine and amisulpride. In patients whose symptomatology cannot be ameliorated by monotherapy, it might be necessary to combine two atypical antipsychotics. While clozapine interacts with a variety of neurotransmitter receptors, amisulpride predominantly binds with high affinity to D3/D2-dopamine receptors. Combination can be considered if a supplementary dopamine-receptor blockade is desired. METHODS: We report on the therapy of 15 patients using a combination regimen of amisulpride and clozapine. Data were collected from patient records. The case reports document previous treatment attempts, describe the reason for the combination therapy, and determine its effect. RESULTS: Major (six cases) or at least marked (eight cases) improvement of previously treatment-resistant positive and negative symptoms could be achieved by using a mean clozapine dose of 375 mg/day (serum level 0.38 mg/l) and an amisulpride dose of 527 mg/day. Additionally, by reducing the clozapine dose compared to monotherapy by 24 %, a significant reduction of side effects was observed. CONCLUSIONS: The combination of amisulpride with clozapine considerably enriches the therapeutic arsenal in cases of severe schizophrenic psychoses. Additional prospective studies are needed in order to systematically evaluate this new treatment strategy.     

Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications

OBJECTIVE: The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis. METHOD: Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis. RESULTS: Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine). CONCLUSIONS: Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.     

Time course of dopamine D2 receptor occupancy by clozapine with medium and high plasma concentrations

Most antipsychotics were thought to induce antipsychotic action at an excess of 70% striatal dopamine D2 receptor occupancy, while the clinical dose of clozapine was reported to show less than 60% occupancy. High-dose clozapine could occupy as high as 80% of striatal dopamine D2 receptor in monkey PET studies. Although the time course of dopamine D2 receptor occupancy is an important property of antipsychotics, that by clozapine has not been investigated in a clinical setting. We measured the time course of extrastriatal dopamine D2 receptor occupancy with different doses of clozapine and evaluated whether the measured occupancies fitted the binding theory. Three consecutive PET scans with [11C]FLB 457 were performed for two patients with schizophrenia, chronically taking 600 mg/day and 200 mg/day of clozapine, respectively. Series of occupancies were also measured in combination with fluvoxamine or paroxetine in one patient. Dopamine D2 receptor occupancies were also simulated using individual clozapine plasma data and previously determined in vivo ED50 value. The occupancy of one patient with high plasma concentration (1207 ng/ml at peak time) was around 75% at peak and around 60% after 26 h. Another patient with medium plasma concentration (649 ng/ml at peak time) showed less than 50% occupancy at peak, decreasing to 15% after 25 h. The measured occupancy values fitted well with the simulated occupancy values. At high plasma concentration, clozapine can induce high extrastriatal dopamine D2 receptor occupancy in the human brain, and this finding fitted well with the theoretical estimation.     

长期服用氯氮平血浆药物浓度的稳定性研究

目的：了解长期服用氯氮平患者的血浆药物浓度的稳定性及其影响因素.方法：对305例稳定使用氯氮平治疗1年以上的精神分裂症住院患者,检测3次氯氮平血浆药物浓度.结果：3次氯氮平血浆药物浓度之间波动：〉20.0%者210例,其中〉25.0%者127例,〉50.0%者50例,〉100.0%者7例,有1例波动达到404.2%.在性别、吸烟、联合用药、氯氮平剂量等与氯氮平血浆药物浓度的稳定性有显著关系.结论：长期服用氯氮平的血浆药物浓度的稳定性也可能因性别、吸烟、合并用内科药、氯氮平剂量等的不同而变化.     

精神科住院病人精神药物使用情况调查

目的：了解目前住各精神药物的使用情况。方法：以１９９８年１２月１日为调查日,共调查４所精神病院,１所为全部住院患者,３所为分别随机抽取男女各１个病区的住院患者。用自制的调查表调查当日用药情况,共调查５４９例。结果：住院患者的用药以氯丙嗪和氯氮平最常用,分别为６０．１％和５９．７％,以后依次为氟哌啶醇,和利和奋乃静。结论：由于氯丙嗪和氯氮平较为有效,安全和价廉,故成为临床最常用的精神药物