Ziprasidone: a new atypical antipsychotic

This paper reviews the clinical pharmacology, efficacy and safety of the new atypical antipsychotic, ziprasidone. All published citations regarding ziprasidone were retrieved and reviewed using a Medline^® search (completed for citations to early 2001). In addition, abstracts from recent scientific meetings presenting data not yet published were reviewed. Like other new antipsychotic medications, ziprasidone fits the profile of an atypical agent, exerting efficacy in positive and negative symptoms of psychosis, as well as affective symptoms, with a low risk of neurological and neuroendocrinological side effects. Unlike newer agents, it does not appear to be associated with weight gain in most patients.     

Olanzapine: an atypical antipsychotic for schizophrenia

Olanzapine is a serotonin-dopamine receptor antagonist primarily used in the treatment of psychotic illnesses. It has been shown in numerous large trials to be as equally effective as haloperidol in the acute treatment and maintenance treatment of schizophrenia. However, olanzapine was shown to be more effective than haloperidol in the treatment of negative symptoms and to cause significantly fewer extrapyramidal symptoms. Furthermore, early reports suggest that olanzapine produces less tardive dyskinesia than haloperidol, though longer follow-up data are needed. Current studies have failed to demonstrate the efficacy of olanzapine in the treatment of refractory schizophrenia. One comparison trial of olanzapine versus risperidone has indicated similar efficacy. Clinical trials in acute mania have found olanzapine to be more effective than placebo. However, there is no role for olanzapine monotherapy in bipolar disorder given current studies. Although olanzapine has shown a low rate of extrapyramidal symptoms, it is not without adverse effects. Clinically significant weight gain has been noted with olanzapine in each of the large clinical trials. The degree of weight gain is similar to clozapine and probably greater than that observed with risperidone. The long-term medical consequence of atypical antipsychotic-induced weight gain is not known at this time. While generally considered first-line drugs from an efficacy and adverse effect standpoint, pharmacoeconomic studies are needed to justify the large acquisition cost of olanzapine compared to typical agents.     

An observational study of the effectiveness and safety of intramuscular olanzapine in the treatment of acute agitation in patients with bipolar mania or schizophrenia/schizoaffective disorder

OBJECTIVE: To determine the effect of intramuscular (IM) olanzapine in severely agitated patients. METHODS: This was an open-label multicenter 1-week observational study of IM olanzapine treatment in severely agitated inpatients and psychiatric emergency services with bipolar mania (n = 22) or schizophrenia (n = 52). Mean change from baseline to 2 h post-first injection (LOCF) in agitation was assessed by PANSS-Excited Component (PANSS-EC) (score range: 5-35 points) mean change from baseline to 15, 30, 45, 60, 90, and 120 min post-first injection, and visit-wise mean changes from mixed-model repeated measures analysis of variance. Kaplan-Meier survival curve analyses estimated time to categorical response (rating of 相似文献   

新型非典型抗精神病药齐拉西酮

通过文献检索综述了齐拉西酮的作用机制、药代动力学及临床评价。齐拉西酮是一种安全、有效的非典型性抗精神病药，用于治疗精神分裂症和分裂情感性障碍。     

A review of atypical antipsychotic drugs versus conventional medication in schizophrenia

Atypical antipsychotics are replacing conventional antipsychotics for the treatment of schizophrenia. They are considered to be at least as effective as conventional agents, with most producing fewer extrapyramidal symptoms. This review presents the evidence from published meta-analyses and describes differences in clinical effectiveness and tolerability between conventional and atypical antipsychotic agents. In addition, it discusses some of the more significant adverse effects including tardive dyskinesia, weight gain, diabetes and sudden death. Results from meta-analyses are conflicting, with some finding no significant advantages on measures of efficacy or tolerability for atypical antipsychotics over moderate daily doses of conventional drugs. Other results have shown that some atypical drugs have at least minor efficacy advantages over conventional comparators. Atypical antipsychotics exhibit a much reduced risk for tardive dyskinesia compared with conventional drugs. However, weight gain is more common with some atypical drugs (especially clozapine and olanzapine). Both conventional and atypical antipsychotics have been associated with diabetes, with most reports implicating both clozapine and olanzapine. Finally, atypical antipsychotics (unlike conventional drugs) have little or no effect on QT and are not associated with sudden death.     

新型非典型抗精神病药:鲁拉西酮

鲁拉西酮为一新型非典型抗精神病药,属于苯并异噻唑衍生物,为多巴胺D_2和5-羟色胺2A(5-HT_(2A))受体拮抗剂。2010年10月28日美国食品和药物管理局批准鲁拉西酮上市,其商品名为Latuda,用于治疗成人精神分裂症。鲁拉西酮的有效剂量范围为40～120mg·d~(-1),推荐起始剂量为40mg·d~(-1),一般最大推荐剂量为80mg·d~(-1),应与食物同时服用。鲁拉西酮常见不良反应有嗜睡、静坐不能、恶心、帕金森病以及焦虑。本文对鲁拉西酮的药理作用、药动学、药物相互作用、临床评价和安全性等进行综述。     

Psychiatric Drug Discovery and Development

This new conference on Psychiatric Drug Research was organised by the Strategic Research Institute and was chaired by P McGonigle (Wyeth Research, USA) and D Schoepp (Eli Lilly, USA). The 2-day meeting featured presentations from an international assembly of industrial and academic experts who have significantly contributed to the current body of knowledge in the field of psychotherapeutics. D Weinberger (NIMH, USA) gave an elegant keynote lecture on the application of genomics in psychopharmacology. Other presentations covered the latest technological advances, animal models and mechanistic approaches utilised in drug discovery for neuropsychiatric disorders and reviewed the current status of numerous novel targets resulting from these strategies.     

非典型抗精神病药利培酮的药代动力学研究进展

利培酮(risperidone)是已在中国上市的非典型抗精神病药,由于其疗效肯定,且锥体外系反应及运动功能抑制等药物不良反应少,因而倍受关注。因此本文就利培酮在人体内吸收、分布、代谢、排泄的药代动力学特征,年龄、肝。肾功能损伤等因素对这些过程造成的影响及其他药物的相互作用做一综述。     

Paliperidone extended-release: a review of efficacy and tolerability in schizophrenia,schizoaffective disorder and bipolar mania

Importance of the field: Paliperidone extended-release (ER), a once-daily, oral, atypical antipsychotic, has been available in the USA and the EU for the treatment of schizophrenia for more than 2 years and was recently (July 2009) approved in the USA for treatment of schizoaffective disorder. Additional data on its efficacy and safety, including that for additional indications, is emerging.

Areas covered in this review: This review provides a background on the compound and summarizes recent data available on treatment of schizophrenia, including comparative data with other antipsychotics, and efficacy and safety data from clinical trials in schizoaffective and bipolar disorders.

What the reader will gain: The reader will gain knowledge of the compound and the existing clinical data so far for paliperidone ER.

Take home message: Paliperidone ER is effective for the treatment of schizophrenia and is at present the only antipsychotic approved in the USA for treatment of schizoaffective disorder. Its efficacy and tolerability profile in treating patients with schizophrenia or schizoaffective disorder indicates that paliperidone ER offers an important treatment option among atypical antipsychotic therapy for these patients.     

Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice

The Multidisciplinary Symposium on Head and Neck Cancer focused on the emerging data that underlie optimal treatment for head and neck cancers, with a particular focus on squamous cell carcinoma of the head and neck. In-depth discussions showcased the published Phase II and Phase III data on the treatment of locally advanced disease with both induction chemotherapy and concurrent chemoradiotherapy. Molecular targets of interest and relevance in this tumour type were identified, as were the agents which target these putative proteins or pathways of carcinogenesis. Preliminary results from trials incorporating molecularly-targeted agents have shown a promising role for these compounds in the management of both locally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck. The Symposium brought a clear message. The management of squamous cell carcinoma of the head and neck has evolved considerably, and with the advent of newer chemotherapeutic agents and molecularly targeted therapies, this field will continue to expand over time.     

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review

Importance of the field: Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP).

Areas covered in this review: Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency.

What the reader will gain: RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI.

Take home message: Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.     

The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania

Introduction: Asenapine is a novel antipsychotic drug approved for the treatment of acute schizophrenia, manic, or mixed episodes associated with bipolar I disorder, as a maintenance treatment of schizophrenia and as an adjunctive therapy with lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.

Areas covered: This review focuses on the preclinical profile of asenapine. It analyzes the pharmacological, neurochemical, behavioral, and molecular mechanisms of asenapine and their contribution to the beneficial therapeutic advantages of the drug as reported in published preclinical and clinical studies, product labels, and poster presentations.

Expert opinion: Asenapine exhibits a broad pharmacological profile that targets a wide range of neurotransmitter receptors with variable affinities. The drug preferentially increases dopamine, norepinephrine, and acetylcholine levels in cortical and limbic brain areas. It also potentiates cortical glutamatergic neurotransmission, and is active in behavioral animal models predictive of antipsychotic, antidepressant, and pro-cognitive activities. Chronic administration of asenapine alters the abundance of dopamine, serotonin, glutamate, adrenergic, and cholinergic receptor subtypes in different brain regions. These action mechanisms of asenapine might contribute to its unique psychopharmacological properties in the improved treatment of schizophrenia and other psychotic disorders.     

Rapid dose initiation of quetiapine for the treatment of acute schizophrenia and schizoaffective disorder: a randomised, multicentre, parallel-group, open study

OBJECTIVE: Rapid resolution of symptoms is a priority for clinicians treating acute psychosis, and rapid initiation of pharmacotherapy may prove beneficial. This study examined rapid dose initiation of quetiapine in acutely ill patients. METHODS: A 2-week, multicentre, randomised, parallel-group, open study. Inpatients (n = 269) diagnosed with schizophrenia or schizoaffective disorder received rapid (n = 139) or conventional (n = 130) initiation of quetiapine, followed by flexible dosing (maximum 800 mg/day). Primary outcome included proportion of patients experiencing > or =1 episode of selected AEs (somnolence, dizziness, orthostatic hypotension) during Week 1. Secondary outcomes included discontinuations due to AEs, and efficacy assessed by BPRS and CGI-S scores. RESULTS: The proportion of patients with > or =1 selected AE during Week 1 was 5.4% and 10.1% in the conventional and rapid initiation groups, respectively. Most common AEs (>5% patients) were hypotension, tachycardia, somnolence and sedation. Overall, four (3.1%) and three (2.1%) patients from the conventional and rapid initiation group, respectively, withdrew due to AEs. BPRS and CGI-S scores decreased significantly (p < 0.001) from baseline in both groups. CONCLUSION: A higher proportion of patients experienced AEs with rapid initiation of quetiapine (800 mg/day by Day 4), although withdrawals due to AEs were comparable. Rapid initiation of quetiapine was generally well tolerated and effective in this setting.     

丙戊酸钠缓释剂辅助治疗兴奋躁动的精神分裂症及分裂情感障碍的研究

目的:评价丙戊酸钠缓释剂(德巴金)辅助治疗兴奋躁动的精神分裂症以及分裂情感障碍的疗效。方法:对符合CCMD-3精神分裂症、分裂情感障碍诊断标准,且以兴奋躁动为主要表现的患者随机分为试验组43例和对照组47例。试验组应用抗精神病药物(氯氮平、奥氮平、利培酮或奎硫平其中之一)联合德巴金(0．5～1．5 g·d-1),对照组单一使用抗精神病药物,观察6周。结果:两组的症状学变化在治疗前后都具有显著性,但是试验组改善比对照组显著(P<0．05～0．01),不良反应组间比较无统计学差异(P>0．05)。结论:德巴金可协助治疗精神分裂症以及分裂情感障碍的兴奋状态。     

罗替戈汀透皮贴剂的研究进展

罗替戈汀为选择性多巴胺D1/D2/D3受体激动剂,其透皮贴剂是第一个非麦角类多巴胺受体激动剂贴剂。罗替戈汀贴剂24h有效,能对帕金森病人持续提供多巴胺能刺激,目前获得FDA和EMA批准上市。对罗替戈汀贴剂研究情况进行简要综述。     

Antipsychotic drug use in neurodegenerative disease in the elderly: problems and potential from a pharmacological perspective

The past decade has seen the introduction of several new antipsychotics for the treatment of schizophrenia. These drugs demonstrate substantially lower levels of extrapyramidal side effects (EPS) than the classical antipsychotics, as well as having (often poorly supported) claims of increased efficacy at ameliorating certain schizophrenic syndromes. Increasingly, these ‘atypical’ drugs are being used in the treatment of psychotic or related behavioural disturbances in patients with neurodegenerative disease. Thus, some newer antipsychotics are particularly valuable in ameliorating the L-dopa-induced psychosis in Parkinson’s disease, while behavioural problems in dementing disorders, such as those occurring in Alzheimer’s disease, are also frequently treated by antipsychotic drugs. The relationship between drug pharmacology and neurotransmitter pathology is essential to understanding the relative efficacy of individual antipsychotic drugs in treating the psychotic and behavioural disturbances of neurodegenerative disorders.     

Oral antipsychotics for the treatment of schizophrenia: heterogeneity in efficacy and tolerability should drive decision-making

Background: Antipsychotic medications are conventionally divided into two groups: First-generation and second-generation antipsychotics (FGAs and SGAs). There is a disagreement about the role of these two groups in the treatment of schizophrenia. Objective: To analyze the reasons for the disagreement and to propose a resolution that would improve the treatment of schizophrenia. Method: An overview of individual SGAs and several FGAs involved in the current disagreement is presented. Effectiveness studies that contributed to the SGAs versus FGAs disagreement are assessed, and meta-analyses of SGAs and FGAs are reviewed. Results/conclusions: Efficacy variations within SGAs and FGAs result in overlaps between the two groups. Regarding safety, FGAs elicit more extrapyramidal side effects and tardive dyskinesia as well as prolactin elevations than SGAs, whereas some SGAs tend to be associated with more weight gain and disturbances in lipid and glucose regulation than FGAs. However, there are again considerable differences between individual agents and overlaps between the two groups in terms of side effects. The classification of antipsychotics into the two groups is no longer useful. The treatment selection for an individual patient should focus on the suitability of an individual antipsychotic for that patient rather than on the group membership of the drug.