Classification of antipsychotic drugs by gene expression in the frontal cortex of mice.

Antipsychotic drugs are classified as typical and atypical based on extrapyramidal effects. However, since the frontal cortex is one of the most important regions for antipsychotic actions, this study attempted to classify antipsychotic drugs based on gene expression in the frontal cortex. Chlorpromazine and thioridazine were selected as typical antipsychotics, and olanzapine and quetiapine as atypical antipsychotics. Since these drugs have similar chemical structures, the effect of the basic structure on gene expression can be eliminated. Cluster analysis of microarray experiments separated 4-drug-administered mice into chlorpromazine-quetiapine and thioridazine-olanzapine groups. This classification scheme is different from that which is based on criteria currently used to group the typical and atypical drugs and suggests that antipsychotic drugs can be further separated into multiple groups.     

2007—2011年盐城市第四人民医院抗精神病药应用分析

目的：了解2007—2011年我院抗精神病药使用情况,以促进临床合理用药。方法：采用回顾性分析法,对2007—2011年我院抗精神病药销售金额、用药频度（DDDs）和限定日费用（DDC）等进行统计、分析。结果：新型非典型抗精神病药的用量逐年上升,5年销售金额增长了2.84倍,DDDs上升了2.53倍;而典型抗精神病药及非典型抗精神病药氯氮平的用量则逐年下降,5年DDDs下降了33.00%。利培酮、阿立哌唑、喹硫平、奥氮平的销售金额及DDDs排序均居前列。2011年抗精神病药的平均DDC比2007年增长了2.26倍,DDC呈现快速增长趋势。结论：我院抗精神病药应用合理,新型非典型抗精神病药的用量呈现增长态势,典型抗精神病药及非典型抗精神病药氯氮平仍是部分患者特别是经济承受能力较低患者的首选药,选用国产和普通剂型的药物有利于降低药物治疗成本。     

我院2009-2012年门诊抗精神病药用药分析

目的：调查我院2009-2012年精神科门诊抗精神病药物的应用情况。方法：采用药物的限定日剂量（DDD）分析法和金额排序法,对我院2009-2012年精神科门诊抗精神病药进行统计分析。结果：抗精神病药使用金额在2010,2011和2012年分别以34.84%,22.24%和16.92%的速度增长;典型抗精神病药用药频度（DDDs）有下降的趋势,非典型抗精神病药DDDs逐年增长。结论：非典型抗精神病药物已广泛应用于精神科临床,成为精神疾病药物治疗的主要药物。     

Basic biology of clozapine: electrophysiological and neuroendocrinological studies

The effects of clozapine and other purported atypical antipsychotics were compared with those of typical antipsychotics within the neuroendocrine axis of the rat. Atypical antipsychotics (e.g., clozapine, thioridazine, melperone, setoperone and RMI 81582) differed from typical antipsychotics (e.g., haloperidol, chlorpromazine, cis-flupentixol and fluphenazine) in that they produced only a brief elevation in serum concentrations of prolactin but marked increases in serum or plasma concentrations of corticosterone and ACTH. Moreover, atypical antipsychotics, but not typical antipsychotics, acutely increased the activity of tuberoinfundibular dopamine neurons, as judged from the accumulation of DOPA in the median eminence after inhibition of decarboxylase activity. The effects of atypical antipsychotics on tuberoinfundibular dopamine neurons and corticosterone secretion were mimicked by neurotensin. It would appear that atypical antipsychotics elicit unique neuroendocrine responses that differentiate these agents from typical antipsychotic drugs.     

Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat.

The alpha1A- and alpha1B-adrenoceptor affinity of the typical (chlorpromazine, haloperidol, pimozide, thioridazine and trifluoperazine) and atypical (clozapine, olanzapine, quetiapine, risperidone and sertindole) antipsychotics was determined by competition binding at alpha1A- and alpha1B-adrenoceptors in rat submaxillary gland and liver. Although all antipsychotics bound to both subtypes with relatively high affinity (K(i)s<74 nM), none were selective (>10-fold). Comparison with published dopamine D2 receptor affinities suggests that antipsychotic blockade of alpha1A- and/or alpha1B-adrenoceptors may contribute to the antipsychotic activity of all the atypical and several of the typical antipsychotics examined.     

Chlorpromazine as a discriminative stimulus in rats: Generalization to typical and atypical antipsychotics

The discriminative stimulus properties of the typical antipsychotic chlorpromazine were examined in a two‐lever drug discrimination procedure for food reward. Six of nine rats readily acquired the discrimination between 1.0 mg/kg chlorpromazine (i.p.) and vehicle in a mean of 29.7 training sessions. The chlorpromazine generalization curve was dose‐dependent and yielded an ED₅₀ of 0.305 mg/kg (95% confidence interval (CI) = 0.201–0.463 mg/kg). The chlorpromazine cue generalized to the atypical antipsychotics clozapine (ED₅₀ for the clozapine curve was 0.258 mg/kg [95% CI = 0.047–1.420 mg/kg]) and olanzapine (ED₅₀ for the olanzapine curve was 0.199 mg/kg [95% CI = 0.076–0.522 mg/kg]) and to the typical antipsychotic thioridazine (ED₅₀ for the thioridazine curve was 3.103 mg/kg [95% CI = 1.993–4.832 mg/kg]). Haloperidol (a typical antipsychotic) and raclopride (an atypical antipsychotic) did not substitute for chlorpromazine. It is clear from the present results that the discriminative stimulus properties of chlorpromazine share similarities both with the atypical antipsychotics clozapine and olanzapine and with the typical antipsychotic thioridazine. The extent to which the discriminative stimulus properties of antipsychotic drugs reflect or are predictive of their therapeutic effects in schizophrenic patients remains unclear. Drug Dev. Res. 48:38–44, 1999. © 1999 Wiley‐Liss, Inc.     

Short-acting parenteral antipsychotics drive choice for classical versus atypical agents

OBJECTIVE: The objective of this study was to investigate which antipsychotics (classical versus atypical) are prescribed in a psychiatric hospital and which determinants affect the choice for one of these two classes of antipsychotics in newly admitted patients. METHODS: In a retrospective cohort design, 522 newly admitted patients were followed from the date of admission until discharge from the hospital. In the cohort of newly admitted patients treated with an oral antipsychotic, a nested case-control study was conducted considering recipients of an atypical agent as cases. Controls were all other cohort members. The association of patient characteristics and the choice between classical versus atypical antipsychotics was studied using logistic regression analysis. The same analysis was performed with adjustment for possible confounding factors (age group, gender, DSM-IV diagnoses, use of short-acting parenteral antipsychotic, global assessment of functioning score, involuntary admissions and involuntary measures). RESULTS: Patients treated with classical oral antipsychotics were more often previously treated with short-acting parenteral antipsychotics than patients treated with atypical antipsychotics (40.8% vs 15.2%; adjusted OR=0.20 95% CI=0.09-0.44). No statistically significant difference was found between patients with different severities of disease. DISCUSSION: Availability of injectable forms seems to drive the choice for oral antipsychotic agents. Future introductions of short-acting parenteral atypical antipsychotics may have a large impact on first-choice oral antipsychotic treatment.     

我院2003-2006年抗精神病药用药分析

目的 了解医院抗精神病药的应用情况,为合理用药提供科学依据.方法 对重庆市精神卫生中心2003-2006年消耗的抗精神病药用药金额、用药频度及日均费用的变化进行统计、分析.结果 与2003年相比,2004与2005年该院抗精神病药销售总金额逐年下降,2006年销售总金额有大幅度的上升;4年中非典型抗精神病药用药金额所占比例逐年上升,而典型抗精神病药用药金额所占比例迅速下降;用药频度最高的为舒必利;用药金额最大的为维思通.结论 该院4年间抗精神药的应用基本合理,用药水平的变化趋势与现代治疗需要的变化一致.     

Risperidone-induced retrograde ejaculation: case report and review of the literature

Medication adherence with antipsychotics is adversely impacted by the burden of untoward adverse effects. In particular, sexual side-effects may interfere with compliance, but are often underreported by patients. Sexual dysfunction related to hyperprolactinemia is commonly described, but ejaculatory disturbance due to potent alpha1 adrenergic antagonism may also occur, and has been reported frequently with certain typical antipsychotics such as thioridazine, but rarely with atypical antipsychotics. Presented here is the case of a 51 year old male with schizophrenia who developed retrograde ejaculation on high dose risperidone therapy (8 mg/day) with prompt resolution of symptoms upon dose reduction. The absence of decreased libido or erectile dysfunction indicates that alpha1 adrenergic antagonism and not low serum testosterone due to hyperprolactinemia is the etiology for this side-effect. This case illustrates another mechanism for sexual adverse effects, and the need for routine inquiry into sexual dysfunction during atypical antipsychotic therapy.     

Quetiapine-induced diabetes with metabolic acidosis

Medication adherence with antipsychotics is adversely impacted by the burden of untoward adverse effects. In particular, sexual side-effects may interfere with compliance, but are often underreported by patients. Sexual dysfunction related to hyperprolactinemia is commonly described, but ejaculatory disturbance due to potent alpha1 adrenergic antagonism may also occur, and has been reported frequently with certain typical antipsychotics such as thioridazine, but rarely with atypical antipsychotics. Presented here is the case of a 51 year old male with schizophrenia who developed retrograde ejaculation on high dose risperidone therapy (8 mg/day) with prompt resolution of symptoms upon dose reduction. The absence of decreased libido or erectile dysfunction indicates that alpha1 adrenergic antagonism and not low serum testosterone due to hyperprolactinemia is the etiology for this side-effect. This case illustrates another mechanism for sexual adverse effects, and the need for routine inquiry into sexual dysfunction during atypical antipsychotic therapy.     

Diabetes mellitus and antipsychotic treatment in the United Kingdom.

OBJECTIVE: Treatment-emergent diabetes has been reported during exposure to conventional and atypical antipsychotics. This retrospective cohort study explored the UK General Practice Research Database (GPRD) to determine hazard ratios of diabetes for patients prescribed antipsychotics. METHODS: A Cox proportional hazard regression model using age, gender, and obesity (BMI > 30 kg/m2) was used to determine the hazard ratio (HR) of diabetes development in conventional antipsychotic (N = 59,089), atypical antipsychotic (N = 9053), individual antipsychotic, and general patient population cohorts (N = 1,491,548). RESULTS: Compared with the general GPRD patient population, patients exposed to conventional or atypical antipsychotics had a higher risk of developing diabetes (atypical antipsychotic cohort: HR = 2.9, CI = 2.0-4.4; and conventional antipsychotic cohort: HR = 1.9, CI = 1.6-2.3). The risk of developing diabetes during thioridazine, risperidone, or olanzapine treatment was significantly higher compared with the general GPRD patient population. CONCLUSION: Consistent with other epidemiology studies, this study supports an increased risk of developing diabetes during treatment with antipsychotics.     

Effects of antipsychotic drugs on operant responding after acute and repeated administration

RATIONALE: The current generation of atypical antipsychotic drugs represents an improvement over traditional ("typical") antipsychotics in many respects. However, a theoretical framework and adequate preclinical models have not yet been developed to predict or explain differences among the atypical antipsychotics, a necessary component of future development. OBJECTIVES: The purpose of the present set of experiments was to identify differences between the acute and subchronic effects of several atypical antipsychotic drugs and the typical antipsychotic haloperidol on operant responding in rats. METHODS: The effects of haloperidol and the atypical antipsychotics clozapine, olanzapine, risperidone, sertindole, quetiapine, remoxipride, and thioridazine were determined in rats trained to respond for food reward under a multiple fixed ratio 30/fixed interval 60 s schedule. A profile of the acute effects of each drug on response rates, response durations, and within-session effects were determined. Next, the dose of each drug that produced 75% suppression of response rates was administered for 16 consecutive days to determine whether or not tolerance would develop to the rate-suppressing effects of that dose. RESULTS: All drugs produced dose-related decreases in response rates. Only haloperidol and risperidone produced significant increases in response duration, while only haloperidol and remoxipride displayed within-session response decrements. Tolerance was evident for clozapine and to a lesser extent thioridazine. CONCLUSIONS: These results illustrate that the current generation of atypical antipsychotics are a heterogeneous group and that operant procedures may be useful for identifying differences preclinically. Specifically, clozapine appears to possess properties that distinguish it from other atypical antipsychotics, particularly after repeated dosing.     

我院2005-2010年住院患者抗精神病药应用分析

目的:分析我院抗精神病药的应用情况。方法:采用回顾性方法,对我院2005-2010年住院患者抗精神病药的应用情况进行统计、分析。结果:我院抗精神病药销售金额和用药频度(DDDs)逐年增加,销售金额从588329元逐年上升至5312869元、DDDs从237176日逐年上升至528822日。其中,经典抗精神病药的销售金额呈下降趋势,非经典抗精神病药的销售金额呈上升趋势。结论:疗效好、副作用小的非经典抗精神病药有逐渐取代经典抗精神病药的趋势。     

Antipsychotic drugs in mania: factors predicting use of antipsychotic medication following inpatient treatment of mania

Inpatients treated for mania are frequently discharged on antipsychotics. There has been disagreement in clinical guidelines concerning their use, and there is little knowledge of the factors predicting this. The aim of the present study was to identify those factors predicting discharge on typical antipsychotic medication after hospital admission for mania. Data were collected retrospectively from the hospital notes of 74 patients who had 100 consecutive psychiatric hospital admissions for mania during the 1990s. Univariate and multivariate analyses were used to estimate odds ratios. The rate of discharge on typical antipsychotics was 71.6% (53 out of the 74 episodes included in the analyses) (95% confidence interval 61.3-81.9). Three factors were found to predict this with odds ratios significant at the P<0.05 level: (i) use of typical antipsychotics during the first week of admission [odds ratio (OR)=13.3]; (ii) voluntary admission (OR=4.2); and (iii) male gender (OR=8.4). There was no evidence that psychotic symptoms or aggressive behaviour were associated. In conclusion, the use of antipsychotics early in the episode strongly predicted discharge on antipsychotics. It appears that clinicians use antipsychotics for their anti-manic effects and patients are often thought to still need the drugs at the time of discharge.     

2011～2014年我院门诊抗精神病药应用分析

目的对我院门诊抗精神病药的用药情况进行调查、统计和分析,为患者及医生提供更好的合理用药服务。方法采用药物利用研究方法,对2011~2014年我院门诊抗精神病药的用药金额、日用药金额(DDC)和用药频度(DDDs)等指标进行统计分析。结果我院门诊各年度的抗精神病药的销售金额年均增长率为6.49%,DDDs年均增长率为4.91%,两者上升趋势明显;非典型抗精神病药(atypical antipsychotics)DDDs排序始终占据前列,最高达86.27%。结论我院门诊抗精神病药使用情况较为合理。非典型抗精神病药已经成为临床上治疗精神障碍的一线用药,而典型抗精神病药(typical antipsychotics)的使用则逐年递减。