非典型抗精神病药易致女性体重增加

据英国路透社2009年4月21日报道。阿尔茨海默病病人服用二代抗精神病药物（也称非典型抗精神病药,如利培酮、奥氮平、喹硫平等）后,会出现体重增加、血脂紊乱等不良反应。     

抗精神病药物所致体重增加与护理干预

目的探讨传统抗精神病药物（氯丙嗪或氯氮平）和新型抗精神病药物（利培酮或阿立哌唑）对精神分裂症患者体重的影响以及实施护理干预的效果。方法选取78例住院精神分裂症患者,分两组分别服用传统抗精神病药物和新型抗精神病药物,测定8周后体重变化。然后采取护理干预,8周后对体重再测定。结果服药8周后,两组体重均较基础体重有显著增加,但两组间比较无显著差异（T=1．08,〉0．05）。经护理干预后,两组体重均显著下降。结论抗精神病药物可导致体重增加,护理干预可减轻该副作用。     

非典型抗精神病药奥兰扎平致体重增加和高血脂

礼来公司近期发出一份“致医师公开信”,就其上市的非典型抗精神病药奥兰扎平（olanzapine,Zyprexa）提出警告：青春期患者使用该药时,较成年患者更具体重增加和血脂升高的风险。该药为一种多巴胺、5-羟色胺和毒蕈碱受体拮抗剂,于1996年在美国首次上市,用于成年精神分裂症、双相障碍型精神病或抑郁症以及普通精神病和抑郁症患者,并于2009年12月获准用于治疗13～17岁的青春期精神分裂症和双相Ⅰ型障碍所致躁狂型或混合型发作患者,其推荐的起始剂量低于致成年患者发生不良反应的最小剂量。     

抗精神病药使体重增加之谜的线索

近年来广泛应用的非典型抗精神病药（AAPD）的代谢副作用引起人们的关注，但是AAPD复杂的药理活性使得确定其内在机制很困难。Snyder等揭示了这一谜团，证明下丘脑组胺1受体拮抗食欲激动酶AMP-蛋白激酶（AMPK）的活化是AAPD氯氮平和奥氮平增强食欲的基础。     

非典型抗精神病药物的副作用

抗精神病药物代谢副作用从上世纪开始已引起人们的关注，但主要是研究其对神经系统的作用。随着副作用案例的增多，人们发现其导致糖尿病的副作用更严重。本文检索Medline 1996年至2003年6月有关氨磺必利、阿立哌唑、氯氮平、奥氮平、喹硫平、利培酮、齐拉西酮及佐替平致糖尿病的文献报道，总结了这些药物的副作用及可能的作用机制，并为如何选用这些药物及用药期间注意事项提出了建议。     

非典型抗精神病药物不良反应的比较

非典型抗精神病药物在疗效、安全性、耐受性等各方面优于传统抗精神病药物;但仍不可避免地存在一定不良反应。本文从中枢神经、心血管、代谢和内分泌、消化以及血液等系统对氯氮平、利培酮、奥氮平、奎硫平和阿立哌唑的不良反应进行比较。     

非典型抗精神病药物的研究进展

［摘要］查阅近年来有关非典型抗精神病药物的国内外文献。从药物作用机制和构效关系方面综述非典型抗精神病药物的最新研究进展。目前非典型抗精神病药物主要分为三大系列：①具有代表性的非典型抗精神病药物;②已经进入临床研究的非典型抗精神病药物;③潜在的非典型抗精神病药物。多巴胺受体基因的多态性在精神病治疗中起到重要的作用,是新的非典型抗精神病药物设计的研究方向。随着分子药理学和组合化学的发展、药物设计理论的进一步完善以及计算机辅助药物设计技术的广泛应用,越来越多的新型非典型抗精神病药物将会在更短的时间内应用于临床,更好地服务患者。     

非典型抗精神病药物的不良作用

为了解非典型抗精神病药物的不良作用,检索国外有关文献中临床试验的数据,比较典型与非典型抗精神病药物之间,及各种非典型抗精神病药物之间不良作用的差异.非典型药物致锥体外系综合症(EPS)、迟发性运动障碍(TD)发生率均低于典型药物;一般非典型药物血中催乳激素增高低于典型药物.其他不良作用的发生率可能与典型药物相同.非典型药物引起患者体重增加是值得关注的问题,在非典型药物之间,不良作用发生的类型、严重程度均有差异,临床医生选择用药应个体化.     

非典型抗精神病药物与代谢综合征相关性分析

目的探讨应用非典型精神病药物治疗时与代谢综合征发生率影响的情况。方法选择我院精神科住院患者160例,分组应用不同药物治疗后对其餐后血糖、腹围、血压、血脂等指标进行检测。结果治疗8周末对4组患者代谢综合征的患病情况进行比较,差异无统计学意义(P>0.05);但齐拉西酮与利培酮患病率比较有明显差异(P<0.05),有统计学意义。其他组比较无明显差异(P<0.05)。第4、第8周4组患病率比较差异无统计学意义(P>0.05),组内比较,喹硫平组、利培酮组、阿立哌唑组治疗第4、第8周比较有统计学差异(P<0.05)。结论不同的非典型抗精神病药物对代谢综合征的影响也不相同,应对患者加强健康指导,适度运动、合理饮食,对体质量进行控制,提高其治疗的依从性。     

非典型抗精神病药物不良反应的性别差异

常用的非典型抗精神病药物有:阿立哌唑、氯氮平、奥氮平、奎硫平、利培酮及齐拉西酮.非典型抗精神病药物的药代动力学和不良反应均有性别差异.女性的CYP1A2酶的活性较男性低,致氯氮平和奥氮平的血药浓度高于男性.利培酮引起女性高催乳素水平,导致女性骨质疏松和性功能障碍的发生率高于男性.研究表明,非典型抗精神病药物使女性代谢综合征的发生率明显高于男性.其中女性和男性肥胖症、高血压、三酰甘油血症及高密度脂蛋白降低的发生率分别为76.3%和35 5%,46.9%和47.2%,42.2%和50.7%,48.9%和63.3%;女性和男性高血糖[≥100 mg/dl(5.55 mmol/L)和≥110 mg/dl(6.10 mmol/L)]的发生率分别为30.0%和21.7%,24.2%和14.1%.非典型抗精神病药物引起心电图QTc间期延长及锥体外系症状女性较男性多见;其中某些药物对胎儿有不良影响.     

Atypical antipsychotics and hyperglycaemia

Hyperglycaemia is known occasionally to occur with conventional neuroleptics, but has more recently been associated with atypical antipsychotics especially clozapine and olanzapine. This article examines more closely this association. A review of relevant published literature from 1970 to date was undertaken following Medline and Embase searches in June 2000. Hyperglycaemia with clozapine was widely reported: spontaneous reports of either hyperglycaemia or ketoacidosis were described in a total of 17 people. In a five-year naturalistic study, 30.5% of patients taking clozapine were eventually diagnosed with Type 2 diabetes. With olanzapine, a total of 10 cases of hyperglycaemia and 5 cases of ketoacidosis have been published. Reports of hyperglycaemia with other atypicals are relatively scarce. The association of hyperglycaemia or ketoacidosis with clozapine and olanzapine appears to be a true drug-induced effect. Risk factors may include male gender, age of around 40 years and being non-Caucasian. The management of hyperglycaemia depends on the causative agent. With clozapine, treatment with oral hypoglycaemics has been successful. With olanzapine, other atypical antipsychotics may be considered. Blood glucose monitoring is essential for all patients starting clozapine or olanzapine.     

Atypical antipsychotics]

This paper synthetizes important information concerning principal atypical antipsychotic drugs actually used in clinical practice: classification, pharmacokinetics, therapeutic uses, side effects, contra-indications and drug interactions. These molecules have heterogeneous structures, but are more and more used because of good neurological tolerance, greater efficacy against negative symptoms, and for clozapin greater efficacy against resistant schizophrenia.     

非典型抗精神病药物与锥体外系症状

为了解非典型抗精神病药物引起锥体外系症状(EPS)的情况,利用Medline检索系统对已公开发表的临床随机对照试验与流行病学资料进行分析。非典型抗精神病药物间引起EPS的程度各有差异,有的与剂量相关,总体较经典的抗精神病药物发生率低,严重程度轻。但临床仍应重视锥体外系症状的预防与治疗问题。     

Atypical antipsychotics in mood disorders

Bipolar disorder is ranked as the sixth most important worldwide cause of disability. Current treatment is based chiefly on lithium and/or anticonvulsants, of which sodium valproate is the most widely used. A significant minority of patients fail to respond fully to current treatments, particularly those with mixed mania and/or rapid cycling. Many patients are unable to tolerate the side-effects of current therapy in the long term, and adverse effects may contribute to the high rate of noncompliance observed in bipolar disorder. The shortcomings of current treatments are reflected in poor outcomes: two-thirds of patients with bipolar disorder require hospitalization on more than one occasion; employment and social functioning are significantly lower than in control groups; 93% of carers suffer at least moderate distress; and 25-50% of patients are believed to attempt suicide at least once. Bipolar disorder shares some features with schizophrenia, and several atypical antipsychotics have demonstrated efficacy in bipolar disorder. Quetiapine has a particularly favourable tolerability profile, with placebo-level extrapyramidal symptoms and prolactin levels across the entire dose range combined with a neutral effect on weight during long-term use, and may be a valuable treatment option in acute mania and bipolar disorder.     

Effects of an educational intervention on weight gain in patients treated with antipsychotics

BACKGROUND: Increasing numbers of reports have raised concerns about significant increases in weight and adiposity over both short- and long-term treatment in patients treated with antipsychotics (APs). The management of overweight and obesity in patients treated with APs has included pharmacological interventions, dietary suggestions, and behavioral strategies. Nevertheless, current evidence does not support the use of pharmacological management of this specific type of obesity, and only a limited number of studies have been published regarding prevention and treatment of weight gain with other strategies. OBJECTIVE: The aim of this study was to evaluate the effectiveness of an educational intervention (EI) that combines low-calorie diet with increased physical activity to prevent and treat weight gain in patients treated with APs. METHOD: Data were from 53 subjects whose body mass index (BMI) had increased by more than 7% after starting an AP therapy and who consented to participate in a 12-week educational intervention study aimed at preventing further weight gain and, when possible, at inducing a weight loss. Weight and BMI were measured at baseline (at each of the monthly follow-up visits) and at study completion 12 weeks from entry in the study. RESULTS: Twenty-six patients completed the 12-week program. Completers showed a significant mean body weight decrease of 3.15 kg, with a mean BMI reduction of 1.2 (kg/m) at the end of the 3-month period. CONCLUSIONS: Educational intervention can be an important tool for the management of weight increase in patients treated with APs. A larger prospective and controlled study is now needed to confirm our findings.     

Atypical antipsychotics in older adults.

Psychotic symptoms are common in older adults and reflect a variety of psychiatric and medical conditions. Antipsychotic drugs form the core of the treatment of these symptoms; however, treatment of the elderly is complicated by a high frequency of comorbid medical illnesses, risk of side effects, and age-related changes in pharmacodynamics and pharmacokinetics. The superior safety and efficacy of atypical antipsychotics makes them first-line agents for managing psychotic patients with schizophrenia. Their uses now extend to other conditions such as schizoaffective disorders, delusional disorder, and mood disorders with psychotic features. Although the drugs have been studied extensively in young subjects, well-designed, double-blind, placebo-controlled studies are relatively lacking in the elderly. Our knowledge of their safety, efficacy and dosage in older adults is based on a few studies with small samples or extrapolated from studies of younger patients. Several psychiatric and medical conditions that are associated with psychotic symptoms in older people are reviewed, as well as how these patients may benefit from treatment with these agents.