Ziprasidone for the treatment of acute manic or mixed episodes associated with bipolar disorder

Ziprasidone, a benzisothiazolyl piperazine-type atypical antipsychotic agent, has a unique receptor-binding profile. A potent antagonist of serotonin 5-HT(2A) and dopamine D(2) receptors, ziprasidone has an affinity for 5-HT(2A) receptors >10-fold higher than its affinity for D(2) receptors.Ziprasidone has been shown to be effective in the treatment of bipolar disorder in patients experiencing manic or mixed episodes. It was significantly more effective than placebo in improving manic symptoms as early as day 2 of treatment in two 3-week placebo-controlled trials as monotherapy. In a 12-week, placebo-controlled trial of patients with acute mania, ziprasidone as monotherapy showed comparable efficacy with, and fewer movement-related adverse events than, haloperidol. It has demonstrated efficacy in two 1-year open-label extension trials, both as monotherapy and in combination with lithium.Ziprasidone has a generally favourable adverse effect profile. In short-term placebo-controlled trials, there were similar discontinuation rates in active treatment and placebo recipients. While twice as many patients treated with ziprasidone compared with placebo discontinued therapy because of adverse events, the number of events was small and adverse effects were generally mild or moderate. The favourable tolerability of ziprasidone has been confirmed in long-term extension studies and its use was not associated with weight gain or dyslipidaemia. Ziprasidone-related movement disorders occurred infrequently.     

Practical guidance for prescribing ziprasidone in acute manic or mixed episodes of bipolar I disorder

INTRODUCTION: Limited information is available on the clinical issues and strategies for optimal clinical usage of ziprasidone in the treatment of adult patients with acute manic or mixed episodes of bipolar disorder. AREAS COVERED: To address those issues, information from clinical trials addressing the efficacy and tolerability of ziprasidone in acute bipolar mania was reviewed and supplemented with the input from an expert faculty of European psychiatrists with extensive experience in treating patients with bipolar mania, both in clinical trials and in everyday clinical practice. EXPERT OPINION: Effective use of oral ziprasidone in the treatment of acute bipolar mania requires rapid titration to doses in the range 120 - 160 mg/day and administration with meals of ≥ 500 kcal. As in the clinical trials, temporary short-term use of benzodiazepines (in particular lorazepam for agitation or temazepam for insomnia) could be advisable. Available evidence from randomized clinical trials in combination with clinical experience supports the use of ziprasidone as one of the first-line effective and safe treatments for acute manic or mixed episodes associated with bipolar I disorder.     

Safety and efficacy of olanzapine monotherapy and olanzapine with a mood stabilizer in 18-week treatment of manic/mixed episodes for Japanese patients with bipolar I disorder

Abstract

Objective:

To assess the safety and efficacy of 18-week olanzapine monotherapy in Japanese patients with bipolar mania, following a 6-week, placebo- and haloperidol-controlled double-blind study (acute study). For those who discontinued the acute study due to lack of efficacy, safety and efficacy was assessed with a combination therapy of olanzapine and a mood stabilizer.     

喹硫平与丙戊酸钠治疗双相情感障碍躁狂急性发作的对照研究

目的比较喹硫平与丙戊酸钠治疗双向情感障碍躁狂急性发作的疗效及安全性。方法2007年至2009年在上海市精神卫生中心因双相情感障碍躁狂急性发作住院患者70例,随机分为喹硫平组和丙戊酸钠组,两组分别接受喹硫平（一日400～800mg）与丙戊酸钠缓释片（一日500～1500mg）,治疗4周,以躁狂量表（BRMS）评定疗效,不良反应量表（TESS）评定不良反应。结果两种药物均能有效缓解躁狂发作,组间疗效差异无统计学意义,但喹硫平组起效较丙戊酸钠组快,治疗l周喹硫平组患者症状即获得有效缓解。喹硫平组不良事件病例数较丙戊酸钠组少,两组均未见严重不良事件。结论短期治疗中,喹硫平比丙戊酸钠治疗双相情感障碍躁狂急性发作起效快、不良反应少。     

Aripiprazole: in acute mania associated with bipolar I disorder

Aripiprazole, an oral quinolinone (carbostyril), is a novel atypical antipsychotic that has partial agonist activity at dopamine D(2) and serotonin 5-HT(1A) receptors, and antagonist activity at 5-HT(2A) receptors. Aripiprazole had a rapid onset of action (as early as day 4) and was effective in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. Aripiprazole was generally significantly more effective than placebo in improving manic symptoms (as defined by a mean change in Young Mania Rating Scale Total Score) in 3-week placebo-controlled trials, and demonstrated superior effectiveness to haloperidol (response rate 50% vs 28.4% in patients remaining on treatment) in a 12-week comparative trial. The time to relapse of symptoms in stabilised patients with bipolar I disorder who previously experienced a manic episode was significantly longer with aripiprazole than with placebo in a 26-week relapse prevention study. Aripiprazole was generally well tolerated and was not associated with weight gain, serum prolactin elevation or clinically significant QTc interval prolongation. black triangle Changes from baseline in extrapyramidal symptom scale scores with aripiprazole were small (<0.5 units), but generally significantly greater than with placebo in one of the 3-week trials. In the 12-week trial, changes from baseline were significantly smaller with aripiprazole than with haloperidol.     

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.     

非典型抗精神病药物用于儿童和青少年双相情感障碍急性躁狂发作和混合发作治疗进展

近年来,双相情感障碍(BD)在儿童和青少年中越来越常见.药物治疗联合心理干预有益于治疗和稳定患者情绪,非典型抗精神病药物(SGA)用于儿童和青少年双相情感障碍急性躁狂发作和混合发作有效.本文简要综述近年来多种SGA用于儿童和青少年BD急性躁狂发作和混合发作治疗的疗效和耐受性研究.     

Drug treatments for bipolar disorder: 1--Acute manic or depressive episodes

Bipolar disorder is a severe, chronic mental illness characterised by repeated episodes of mania or hypomania, depression or mixed affective states. Depending on the clinical context, treatment may involve drugs, psychological therapies, social interventions and/or electroconvulsive therapy (ECT). Here we concentrate on the role of drug treatments for acute manic or depressive episodes in adults with bipolar disorder. A second article will consider their role as maintenance and preventive therapy, and in special situations such as pregnancy.     

Frequency of hospitalisations and inpatient care costs of manic episodes: in patients with bipolar I disorder in France

BACKGROUND: Bipolar disorder is a chronic illness that may involve multiple relapses and result in substantial psychosocial impairment. However, very few recent studies have investigated the economic burden of the disease. OBJECTIVE: To assess the frequency of hospitalisation and the inpatient care costs associated with manic episodes in patients with bipolar I disorder in France. METHOD: A cost-of-illness study was conducted based on available data using a hospital payer perspective. The lifetime prevalence of manic episodes was estimated from published epidemiological data using a random-effects meta-analysis. Data were obtained by a computerised literature search using the main scientific and medical databases. Additional epidemiological references were identified from published studies and textbooks. Data on frequency of hospitalisation and length of stay were collected from a large psychiatric university hospital. Data on unit costs for inpatient care were obtained from the accounting system of the largest hospital group in Paris, France for the year 1999. RESULTS: Extrapolating from international data on the average prevalence of bipolar I disorder, the proportion of rapid cycling patients and the average cycle duration, we estimated the annual number of manic episodes in patients with bipolar I disorder to be around 265,000 in France. Based on hospital data in Paris, the proportion of manic episodes that require hospitalisation was estimated to be around 63%. The average length of stay was 32.4 days and the hospitalisation-related costs were estimated to be around 8.8 billion French francs (Euro 3 billion) [1999 values]. CONCLUSION: Our study highlights the lack of medical and economic data on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France. As the lifetime prevalence of bipolar I disorder may be as high as 3% among adults, further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar I disorder in France.     

齐拉西酮与奎硫平合并碳酸锂治疗双相情感障碍躁狂发作对照研究

目的探讨齐拉西酮合并碳酸锂治疗双相情感障碍躁狂发作的疗效和安全性。方法将80例双相情感障碍躁狂发作患者随机分为齐拉西酮联合碳酸锂治疗组（研究组）和奎硫平联合碳酸锂治疗组（对照组）各40例。观察4周。分别采用杨氏躁狂量表（YMRS）、治疗中出现的症状量表（TESS）评定疗效和不良反应。结果治疗4周,研究组痊愈率为20.00%,总有效率为85.00%;对照组分别为25.00%和87.50%,两组比较,差异无统计学意义（P〉0.05）。两组YMRS评分治疗前差异无统计学意义（P〉0.05）,治疗后各周均有显著下降（P均〈0.01）,两组比较,差异无统计学意义（P〉0.05）。研究组和对照组不良反应发生率分别为42.50%和47.50%,差异无统计学意义（P〉0.05）,研究组静坐不能、肌张力增高的发生率高于对照组（P均〈0.05）,体质量增加发生率低于对照组（P〈0.05）。结论齐拉西酮联合碳酸锂治疗双相情感障碍躁狂发作有良好疗效,不良反应轻微。     

Asenapine as adjunctive treatment for acute mania associated with bipolar disorder: results of a 12-week core study and 40-week extension

In a 12-week randomized, placebo-controlled study evaluating the efficacy and safety of adjunctive asenapine, bipolar I disorder patients experiencing manic or mixed episodes despite pretreatment with lithium or valproate monotherapy were treated with flexible-dose, twice-daily asenapine 5 or 10 mg (n = 158) or placebo (n = 166). The primary efficacy end point was change from baseline Young Mania Rating Scale (YMRS) total score at week 3. Secondary outcomes included YMRS response and remission and Clinical Global Impression for Bipolar Disorder and Montgomery-Asberg Depression Rating Scale score changes. Patients completing the core study were eligible for a 40-week double-blind extension assessing safety and tolerability. Adjunctive asenapine significantly improved mania versus placebo at week 3 (primary end point) and weeks 2 to 12. The YMRS response rates were similar at week 3 but significantly better with asenapine at week 12. The YMRS remission rates and changes from baseline on Clinical Global Impression for Bipolar Disorder for mania and overall illness were significantly better with asenapine at weeks 3 and 12. No other statistically significant differences on secondary outcomes were observed. Only a small number of patients entered the extension, making firm statistical conclusions on efficacy difficult. Treatment-emergent adverse events reported by 5% or more of asenapine patients and at twice the incidence of placebo were sedation, somnolence, depression/depressive symptoms, oral hypoesthesia, and increased weight in the 12-week core study. Adjunctive asenapine to lithium or valproate was more effective than mood stabilizer monotherapy in the core study and was well tolerated for up to 52 weeks.     

齐拉西酮联合心境稳定剂治疗双相障碍躁狂发作和混合发作

目的：研究和探讨齐拉西酮合并碳酸锂或丙戊酸钠治疗躁狂发作和混合发作的疗效和安全性。方法：对符合CCMD-3躁狂发作和混合发作诊断标准的68例研究对象随机分成两组,试验组应用齐拉西酮合并碳酸锂或丙戊酸钠,对照组单一使用碳酸锂或丙戊酸钠,治疗观察6周。采用杨氏躁狂量表（YMRS）评定疗效,以副反应量表（TESS）及实验室有关辅助检查评价安全性。 结果：两组在治疗前后症状均有显著降低（F＝9.05,P＜0.01;F＝6.10,P＜0.01）。齐拉西酮组在治疗第1周末的减分率比对照组显著,这种差异在1~6周持续存在,而且第6周结束后的临床痊愈率也显著高于对照组。研究组1周末、治疗2周末、治疗4周末、治疗6周末YMRS分别是21.4±8.4,14.6±5.5,8.9±3.3,6.5±3.4,对照组分别是23.9±7.2,20.9±8.1,17.8±7.8,12.8±8.9,组间差异有统计学意义（P＜120.01）,试验组的相对变化分别是6.1±3.5,12.9±4.8,20.1±5.3,21.4±5.5,对照组分别是2.1±3.0,6.8±4.5,11.5±5.6,14.4±5.3,组间比较差异有统计学意义（P＜0.01）。两组间有效率差异有统计学差异（68.5%,48.5%, X2=4.47,P＜0.05）。两组间痊愈率也有统计学意义（54.3%, 18.2%, X2=9.52,P＜0.01）。但是两组间均没有严重的药物副作用,因无疗效和副作用导致的脱落率两组差异无显著性。结论：齐拉西酮合并碳酸锂或丙戊酸钠治疗躁狂发作和混合发作双相障碍的疗效比较理想,比单一使用心境稳定剂更好。     

A 12-week, open, randomized trial comparing sodium valproate to lithium in patients with bipolar I disorder suffering from a manic episode

On the basis of 3-week studies, lithium and valproate are both recommended for first-line treatment of acute mania. It is, however, also important to demonstrate that antimanic efficacy can be maintained. This study has been designed to compare the efficacy and tolerability of valproate and lithium over 12 weeks in the treatment of acute mania in patients with type I bipolar disorder. Three hundred patients with bipolar I disorder presenting with acute mania were randomized to open treatment with lithium (starting dose: 400 mg/day) or valproate (starting dose: 20 mg/kg/day) for 12 weeks. The primary efficacy criterion was remission (YMRS score or=2 on the CGI-BP severity scale). Remission rates were 65.5% (lithium group) and 72.3% (valproate group). Noninferiority of valproate with respect to lithium was demonstrated [between-group difference: 6.78% (95% confidence intervals: -3.80 to 17.36%)]. Remission rates assessed by the secondary mixed model repeated measures analysis were significantly greater with valproate than with lithium. Adverse events were reported in 44% of patients in both groups. Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks.     

Aripiprazole for the treatment of bipolar disorder: a review of current evidence

INTRODUCTION: several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission. AREAS COVERED: this paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice. EXPERT OPINION: aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic-maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.     

Aripiprazole for the treatment of bipolar disorder: a review of current evidence

Introduction: Several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission.

Areas covered: This paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice.

Expert opinion: Aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic–maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.