抗精神病药所致高泌乳素血症干预对策的专家共识

高泌乳素血症是抗精神病药常见的不良反应,可导致闭经、溢乳、性功能低下、骨质疏松及代谢异常等不良后果,降低治疗依从性,从而影响治疗转归及结局。本文介绍了抗精神病药所致高泌乳素血症的危险因素、临床表现、诊断、评估、监测及干预对策。     

肠道菌群与抗精神病药所致代谢综合征相关研究进展

第2代抗精神病药在精神分裂症等精神障碍中广泛使用, 长期使用可导致代谢综合征患病风险增高。然而抗精神病药所致代谢综合征的病因机制并不明确, 肠道菌群与代谢紊乱的关系越来越引起重视。有研究显示抗精神病药源性代谢综合征患者具有独特肠道菌群特征, 靶向菌群的探索性治疗有初步临床效益, 肠道菌群可能通过免疫、炎症、神经、基因表达调控等多个方面参与抗精神病药所致代谢综合征的发生发展。本文将对肠道菌群与抗精神病药所致代谢综合征相关性研究进行综述, 为未来病因机制研究和治疗提供思路。     

抗精神病药物诱导代谢紊乱机制的研究进展

抗精神病药物是治疗精神分裂症的主要临床用药,也用于双相障碍、焦虑障碍等其它精神疾病的治疗.但因其明显的代谢紊乱不良反应而严重影响其依从性及疗效.早在1956年Bettie Hiles首次报告了第一代抗精神病药氯丙嗪可引起高血糖,但因其突出的锥体外系综合征等神经系统不良反应,使其代谢异常的副作用没有得到充分关注.     

抗精神病药对分裂症病人记忆的影响

自50年代术期以后,就有证据表明,抗精神病药能损害各种记忆和认知功能。最近有研究提出,抗精神病药损害短时和长时记忆功能,但不损害瞬间记忆;对记忆的损害部分是由抗精神病药的抗胆碱能效应引起。本研究旨在进一步验证抗精神病药中抗胆碱能效应对记忆功能的影响。     

分裂症患者的抑郁,巴金森氏症状及阴性症状

对分裂症患者中阴性症状的病因和分类仍有争议。阴性症状较难判断,并可见于抑郁症或巴金森氏病,因重叠而相混淆。抗精神病药可产生程度不同的巴金森氏症状,某些表现与阴性症状极难分辨。抗胆碱药常用来对抗抗精神病药的副作用,但也可影响阴性症状。为此,作者对45例门诊分裂症患者进行调查,以了解用抗精神病药治疗的分裂症患者中抑郁症状、巴金森氏症状、药物与阴性症状之间的关系。     

一日法调查住院老年精神病患者抗精神病药处方情况

目的了解老年精神病住院患者抗精神病药应用情况。方法采用一日法对北京回龙观医院老年精神痛患者的抗精神病药的处方进行调查。结果（1）单一用药及合并用药中利培酮处方量均第一;（2）新型抗精神病药比典型抗精神病药应用更广泛且以单一抗精神病药为主;（3）抗精神病药的使用剂量均在推荐的安全剂量之下。结论老年患者的抗精神病药的,1名床应用情况发生了较大改变,新型抗精神病药使用越来越广泛,药物选择更趋多样化;对于药物的选择和用量考虑疗效的同时应特别关注老年人药物的耐受性问题。     

EPS与病人的易患性

由于对抗精神病药诱发锥体外综合征(EPS)的预防看法不一,故难以预测EPS的发生。本文选择一年内诊断为精神分裂症并经多种抗精神病治疗的住院病人。排除入院前曾使用口服或长效抗精神病药、扰胆碱能药、三环抗抑郁药及超量用药者。研究包括5年中在同一医院住院、并经多种抗精神病药     

抗精神病药换药期间的撤药综合征

一种抗精神病药换成后一种抗精神病药时,前一种抗精神病药的撤药可引起撤药综合征,这种症状易被误认为是后一种药物的不良反应,应特别注意。抗精神病药的撤药综合征分为4组：多巴胺D2受体超敏综合征;5-FIT2A受体超敏综合征;胆碱受体超敏综合征;组胺H1受体超敏综合征。     

精神药物的不良反应

1抗精神病药所致精神症状 崔英光,孙秀珍：某些抗精神病药在临床应用中,可出现与治疗目的完全相反的精神症状或新的精神症状,现介绍如下。     

抗精神病药物对体外培养胰岛细胞分泌功能影响的比较研究

抗精神病药物(antipsychotic drugs APS),尤其是非典型抗精神病药物(atypical tmtipsychotic drugs AAPS)可以引起血糖血脂等代谢异常[1],具体机制尚不清楚.因此,本研究以目前研究涉及较少的舒必利、氟哌啶醇和氯丙嗪等典型抗精神病药物来探讨APS对离体大鼠胰岛细胞胰岛素分泌功能的影响.     

Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: State-of-the-art and future perspectives

Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia, resulting in a higher mortality rate and shorter life expectancy compared with those in the general population. Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks, antipsychotics, particularly those of second generation, may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia. This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms, monitoring guidelines, and interventions. Nearly all antipsychotics are associated with weight gain, but the degree of the weight gain varies considerably. Although certain neurotransmitter receptor-binding affinities and hormones are correlated with weight gain and specific metabolic abnormalities, the precise mechanisms underlying antipsychotic-induced weight gain and metabolic disturbances remain unclear. Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances. Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed, they are not routinely implemented in clinical care. Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances. Thus, patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs. If lifestyle intervention fails, switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered. Antipsychotic medications are essential for schizophrenia treatment, hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.     

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.     

Chronic clozapine treatment in female rats does not induce weight gain or metabolic abnormalities but enhances adiposity: implications for animal models of antipsychotic-induced weight gain

The ability of clozapine to induce weight gain in female rats was investigated in three studies with progressively lowered doses of clozapine. In an initial preliminary high dose study, clozapine at 6 and 12 mg/kg (i.p., b.i.d.) was found to induce weight loss. In a subsequent intermediate dose study, we obtained no evidence for clozapine-induced weight gain despite using identical procedures and doses of clozapine (1-4 mg/kg, i.p., b.i.d.) with which we have observed olanzapine-induced weight gain, hyperphagia, enhanced adiposity and metabolic changes [Cooper G, Pickavance L, Wilding J, Halford J, Goudie A (2005). A parametric analysis of olanzapine-induced weight gain in female rats. Psychopharmacology; 181: 80-89.]. Instead, clozapine induced weight loss without alteration in food intake and muscle mass or changes in levels of glucose, insulin, leptin and prolactin. However, these intermediate doses of clozapine enhanced visceral adiposity and elevated levels of adiponectin. In a final study, low doses of clozapine (0.25-0.5 mg/kg, i.p, b.i.d.) induced weight loss. These data demonstrate that clozapine-induced weight gain can be much more difficult to observe in female rats than olanzapine-induced weight gain. Moreover, these findings contrast with clinical findings with clozapine, which induces substantial weight gain in humans. Clozapine-induced enhanced adiposity appears to be easier to observe in rats than weight gain. These findings, along with other preclinical studies, suggest that enhanced adiposity can be observed in the absence of antipsychotic-induced weight gain and hyperphagia, possibly reflecting a direct drug effect on adipocyte function independent of drug-induced hyperphagia [e.g. Minet-Ringuet J, Even P, Valet P, Carpene C, Visentin V, Prevot D, Daviaud D, Quignard-Boulange A, Tome D, de Beaurepaire R (2007). Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Molecular Psychiatry; 12: 562-571.]. These and other findings which show that the results of studies of antipsychotic treatment in animals do not always mimic clinical findings have important implications for the use of animal models of antipsychotic-induced weight gain. With regard to weight gain the results obtained appear to depend critically on the experimental procedures used and the specific drugs studied. Thus such models are not without limitations. However, they do consistently demonstrate the ability of various antipsychotics to enhance adiposity.     

Antipsychotic induced weight gain in schizophrenia:mechanisms and management

The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible individual or team; and (iii) the adoption of clear structured protocols for clinicians to follow in case of clinically significant weight gain and metabolic issues, which should incorporate greater collaboration between various health professionals from psychiatric and medical specialist services.     

Developing translational animal models for symptoms of schizophrenia or bipolar mania

Animal models have long been used to explore hypotheses regarding the neurobiological substrates of and treatments for psychiatric disorders. Early attempts to develop models that mimic the entirety of the diagnostic syndromes in psychiatry have evolved into more appropriate efforts to model specific symptoms. Such an approach reflects the facts that even in patients, clinical symptoms transcend diagnostic categories, and the specific etiologies of psychiatric disorders are unknown. An animal model can only be identified adequately by specifying both the manipulation (drug, lesion, strain) used to induce abnormalities and the measure(s) used to characterize them. A wide range of pharmacological, lesion, and developmental manipulations have been combined with various measures of information processing to develop useful animal models that parallel human tests. Prepulse inhibition of startle, event-related potential (ERP) measures of auditory gating, and Cambridge neuropsychological test automated battery (CANTAB) measures of cognition are examples of measures that can be used in both rodents and humans and that are robustly altered in both psychiatric disorders and animals manipulated with appropriate drugs or lesions. The further development of cross-species models is critically important, given the new opportunities for the development and registration of specific treatments for the cognitive disorders of schizophrenia that are not ameliorated by available drugs. In moving beyond the focus on psychotic symptoms to the cognitive symptoms of schizophrenia, animal models that do not involve manipulations of dopamine D(2) receptors but that do utilize information processing measures that are correlated with cognitive disturbances are receiving increased attention. Here, selected examples of how cross-species measures of psychiatric disorders are developed and validated are discussed. Specific animal paradigms that parallel the specific domains of cognition that are altered in schizophrenia provide one focus of the review. Another focus includes efforts to develop new human models of psychiatric symptoms that are designed to parallel existing tests used in rodents.     

Stoffwechselerkrankungen des Erwachsenen und Epilepsie

Metabolic disorders with epilepsy are either acquired or hereditary. Hereditary metabolic disorders with epilepsy are rare in adults. The most frequent are the mitochondrial disorders. Epilepsy is the dominant or only phenotypic feature in metabolic disorders only in rare cases. All types of seizures occur but tonic-clonic seizures and myoclonic seizures prevail. Standard antiepileptic drugs are occasionally effective but are often ineffective. Valproate should be avoided in certain metabolic epilepsies, as it may worsen epilepsy or induce a fatal outcome. Identification of the underlying metabolic defect is essential as specific treatment is available for some of them.     

Dominant-submissive behavior as models of mania and depression

This review examines the ways in which dominant-subordinate behavior in animals, as determined in laboratory studies, can be used to model depression and mania in humans. Affective disorders are mood illnesses with two opposite poles, melancholia (depression) and mania that are expressed to different degrees in affected individuals. Dominance and submissiveness are also two contrasting behavioral poles distributed as a continuum along an axis with less or more dominant or submissive animals. The premise of this article is that important elements of both mania and depression can be modeled in rats and mice based on observation of dominant and submissive behavior exhibited under well defined conditions. Studies from our own research, where dominance and submissiveness are defined in a competition test and measured as the relative success of two food-restricted rats to gain access to a feeder, have yielded a paradigm that we call the Dominant Submissive Relationship (DSR). This paradigm results in two models sensitive to drugs used to treat mood disorders. Specifically, drugs used to treat mania inhibit the dominant behavior of rats gaining access to food at the expense of an opponent (Reduction of Dominant Behavior Model or RDBM), whereas antidepressants counteract the behavior of rats losing such encounters; Reduction of Submissive Behavior Model (RSBM). The validation of these models, as well as their advantages and limitations, are discussed and compared with other animal paradigms that utilize animal social behavior to model human mood disturbances.     

Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway

The exact therapeutic mechanism of action of antipsychotic drugs remains unclear. Recent evidence has shown that second-generation antipsychotic drugs (SGAs) are differentially associated with metabolic side effects compared to first-generation antipsychotic drugs (FGAs). Their proclivity to cause metabolic disturbances correlates, to some degree, with their comparative efficacy. This is particularly the case for clozapine and olanzapine. In addition, the insulin signaling pathway is vital for normal brain development and function. Abnormalities of this pathway have been found in persons with schizophrenia and antipsychotic drugs may ameliorate some of these alterations. This prompted us to hypothesize that the therapeutic antipsychotic and adverse metabolic effects of antipsychotic drugs might be related to a common pharmacologic mechanism. This article reviews insulin metabolism in the brain and related abnormalities associated with schizophrenia with the goals of gaining insight into antipsychotic drug effects and possibly also into the pathophysiology of schizophrenia. Finally, we speculate about one potential mechanism of action (that is, functional selectivity) that would be consistent with the data reviewed herein and make suggestions for the future investigation that is required before a therapeutic agent based on these data can be realized.