碳酸锂联用拉莫三嗪对双相情感障碍快速循环型的疗效研究

目的 探讨碳酸锂联用拉莫三嗪对双相情感障碍快速循环型的疗效。方法 将40例快速循环型患者随机分为实验组和对照组，每组20例。实验组选用碳酸锂联用拉莫三嗪联合治疗，对照组单用碳酸锂治疗，分别于治疗前、治疗第2周、第4周和第6周选用大体评定量表（CGI）和简明精神病评定量表（BPRS）予以评定。结果 实验组在治疗第2周、第4周和第6周CGI评定总有效率分别为27％、48％、76％，显著高于对照组，BPRS评分显著低于对照组。结论 碳酸锂联用拉莫三嗪对双相情感障碍快速循环型具有良好的疗效。     

拉莫三嗪维持治疗双相障碍躁狂发作的疗效评价

目的评价拉莫三嗪维持治疗双相障碍躁狂发作的疗效。方法将73例维持期双相障碍躁狂发作患者随机分为两组，研究组用拉莫三嗪系统治疗，对照组用碳酸锂系统治疗，共治疗12周，并在入组时和治疗后第4、12、24周末评定蹂狂量表（BRMS）和社会功能缺陷筛查量表（SDSS），分别评估躁狂症状严重程度和社会功能受损情况，副反应量表（TESS）评定不良反应。结果在治疗第4周末及第12周末，研究组BRMS和SDSS评分均较治疗前有显著性降低（P〈0.05），而对照组无显著性变化。治疗第4周末、第12周末及第24周末，研究组的BRMS和SDSS评分均显著低于对照组（P〈0.05）。结论拉莫三嗪对双相障碍躁狂发作的维持期治疗有显著疗效，且可有效改善患者的社会功能。     

拉莫三嗪治疗双相抑郁的对照研究

目的 评价拉莫三嗪治疗双相抑郁的疗效和安全性.方法 将62例双相抑郁发作患者随机分为拉莫三嗪组31例,碳酸锂组31例.分别口服拉莫三嗪50～250 mg/d,碳酸锂500～2 000 mg/d,疗程8周,分别于治疗前及治疗后2、4、8周末采用17项汉密尔顿抑郁量表(HAMD)、临床总体印象-严重度量表(CGI-S)进行评定.结果 治疗8周末,两组均取得较好的显效率及有效率,且拉莫三嗪组优于碳酸锂组;两组CGI较治疗前显著减少(P＜0.05),而两组间无统计学意义(P＞0.05).两组HAMD评分与治疗前比较于治疗4周末始,均明显降低(P＜0.05);而且治疗8周末,拉莫三嗪组HAMD评分明显低于碳酸锂组(P＜0.05).拉莫三嗪组不良反应较碳酸锂组少而轻.结论 拉莫三嗪治疗双相抑郁有较好疗效,且安全性较好.     

拉莫三嗪与丙戊酸钠治疗双相抑郁的对照研究

目的评价拉莫三嗪治疗双相障碍抑郁发作的效果和安全性。方法对107例双相障碍抑郁发作患者采用随机、平行分组、对照的方法分别以拉莫三嗪和丙戊酸钠治疗,疗程8周,以汉密尔顿抑郁量表(HAMD)、临床疗效总评量表(CGI)在治疗前和治疗后第1、2、4、6、8周末评价疗效,同时采用治疗时出现的症状量表(TESS)进行安全性评估,在第1、2、4、6、8周末及需要时用Bech-Rafaelsen躁狂量表(BRMS)评定躁狂症状。结果拉莫三嗪组和丙戊酸钠组比较,两组有效率分别为75.5%和51.9%,治疗第6周和第8周末HAMD总分和减分率差异有统计学意义。治疗组不良反应明显较对照组发生率低。结论拉莫三嗪治疗双相障碍抑郁发作疗效优于丙戊酸钠,且前者不良反应较少,安全性高。     

拉莫三嗪治疗双相障碍

拉莫三嗪（Lamotrigine）可使情绪低落正常化，改善双相抑郁较突出；而老一代心境稳定剂（锂、卡马西平和丙戊酸钠）和某些新一代抗精神病药可使情感高涨正常化，改善躁狂或轻躁狂较突出。本文拟综述拉莫三嗪治疗双相障碍的进展。     

奥氮平与碳酸锂治疗躁狂发作的对照研究

目的：比较奥氮平与碳酸锂治疗双相Ⅰ型障碍急性躁狂发作的疗效及安全性。方法：57例符合美国精神障碍诊断与统计手册第4版（DSM-Ⅳ）双相Ⅰ型障碍急性躁狂发作患者随机分为奥氮平组与碳酸锂组。治疗6周。以Bech-Rafaelsen躁狂量表（BRMS）、大体评定量表（GAS）、临床疗效总评量表（CGI）评估疗效,治疗中出现的症状量表（TESS）评定不良反应。结果：奥氮平与碳酸锂疗效相当（P〉0.05）,各有其不良反应。治疗前后TESS量表分,两组间差异无显著性（P〉0.05）。结论：奥氮平治疗双相Ⅰ型障碍急性躁狂发作,疗效和不良反应与碳酸锂无明显差异。     

奥卡西平和碳酸锂治疗双相障碍躁狂发作患者的对照研究

目的：比较奥卡西平和碳酸锂治疗双相障碍躁狂发作的疗效和安全性。方法：70例双相障碍躁狂发作患者随机分为奥卡西平组和碳酸锂组各35例,分别给予奥卡西平和碳酸锂治疗8周。以Bech-Rafaelsen躁狂量表（BRMS）、临床疗效总评量表-病情严重程度（CGI-SI）以及治疗中出现的症状量表（TESS）评定疗效及不良反应。结果：两组治疗后BRMS、CGI-SI评分均较治疗前显著下降（P〈0.05或P〈0.01）;两组间比较差异无统计学意义（P〉0.05）;两组不良反应均为轻度。结论：奥卡西平治疗双相障碍躁狂发作的疗效与碳酸锂相当,不良反应轻。     

拉莫三嗪治疗双相Ⅱ型障碍的临床对照研究

拉莫三嗪是一种苯三嗪衍生物,通过抑制神经原突触前膜的钠离子和钙离子通道,对神经细胞的稳定作用而治疗双相抑郁[1],国外研究发现它不仅作为心境稳定剂,而且还具有较明显的抗抑郁作用,特别对双相抑郁,快速循环等有良好效应。为验证拉莫三嗪对双相Ⅱ型障碍治疗的疗效和安全性,我们进行了临床对照研究,现报道如下:1对象和方法1.1对象为我院2003年2月～2006年10月期间门诊及住院患者,①符合DSM-Ⅳ双相障碍Ⅱ型诊断标准;②全部病例均有一次或以上的轻躁狂发作,最多者达12次,入组时均呈抑郁相;③汉密尔顿抑郁量表(HAMD)24项≥26分;④年龄20～…     

奎硫平治疗双相情感障碍临床分析

目的：评价奎硫平单药治疗及联合碳酸锂治疗双相情感障碍躁狂发作的疗效和安全性。方法：78例双相情感障碍躁狂发作患者随机分成奎硫平单药治疗组（研究组）和奎硫平联合碳酸锂治疗组（对照组）各39例。观察4周。于治疗前以及治疗1、2和4周分别采用杨氏躁狂量表（YMRS）、阳性与阴性症状量表（PANSS）评价疗效;采用不良事件量表、SimpsonAngus量表、Barnes静坐不能评定量表及不自主运动量表评价药物安全性。结果：治疗4周,研究组痊愈率63.89%,有效率94.44%;对照组分别为66.67%和94.44%,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）。研究组不良反应总发生率显著低于对照组（χ2=4.06,P〈0.05）。结论：奎硫平单药治疗双相情感障碍躁狂发作与奎硫平联合碳酸锂治疗疗效相同,且单药治疗不良反应发生率更低。     

喹硫平治疗双相抑郁的对照研究

目的评价喹硫平治疗双相抑郁的疗效和安全性。方法对双相抑郁采用随机分组、对照的方法,分别以喹硫平、碳酸锂治疗,疗程8周,以HAMD、CGI、TESS在治疗前和治疗后第1、2、4、6、8周末评价疗效和安全性,在第1、2,4、6、8周末及需要时用BRMS评定躁狂症状。结果（1）喹硫平和碳酸锂相比较,两组有效率分别为62．5％和58．3％,治疗第6、8周末HAMD总分和减分率差异无统计学意义（P〉0．05）。（2）治疗组不良反应发生率比对照组少（P〈0．05）。结论喹硫平单药使用可有效治疗双相抑郁,减少诱发躁狂的风险。     

A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder

BACKGROUND: Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials. This double-blind, placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder. METHODS: After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued, patients were randomized to lamotrigine (100-400 mg daily), lithium (0.8-1.1 mEq/L), or placebo as double-blind maintenance treatment for as long as 18 months. RESULTS: Of 349 patients who met screening criteria and entered the open-label phase, 175 met stabilization criteria and were randomized to double-blind maintenance treatment (lamotrigine, 59 patients; lithium, 46 patients; and placebo, 70 patients). Both lamotrigine and lithium were superior to placebo at prolonging the time to intervention for any mood episode (lamotrigine vs placebo, P =.02; lithium vs placebo, P =.006). Lamotrigine was superior to placebo at prolonging the time to a depressive episode (P =.02). Lithium was superior to placebo at prolonging the time to a manic, hypomanic, or mixed episode (P =.006). The most common adverse event reported for lamotrigine was headache. CONCLUSIONS: Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode. The results indicate that lamotrigine is an effective, well-tolerated maintenance treatment for bipolar disorder, particularly for prophylaxis of depression.     

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2009

The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications.
The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events.
Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.     

A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder

BACKGROUND: The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression. This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder. METHOD: During an 8- to 16-week open-label phase, lamotrigine (titrated to 200 mg/day) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I outpatients (N = 966) and concomitant drugs were gradually withdrawn. Patients stabilized on open-label treatment (N = 463) were then randomly assigned to lamotrigine (50, 200, or 400 mg/day; N = 221), lithium (0.8-1.1 mEq/L; N = 121), or placebo (N = 121) monotherapy for up to 18 months. The primary outcome measure was time from randomization to intervention (addition of pharmacotherapy) for any mood episode (depressive, manic, hypomanic, or mixed). Data were gathered from September 1997 to August 2001. RESULTS: Time to intervention for any mood episode was statistically superior (p = .029) for both lamotrigine and lithium compared with placebo-median survival times were 200, 170, and 93 days, respectively. Intervention for depression was more frequent than for mania by a factor of nearly 3:1. Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode (p = .047). The proportions of patients who were intervention-free for depression at 1 year were lamotrigine 57%, lithium 46%, and placebo 45%. Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode (p = .026). The proportions of patients who were intervention-free for mania at 1 year were lamotrigine 77%, lithium 86%, and placebo 72%. Headache was the most frequent adverse event for all 3 treatment groups. CONCLUSION: Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients, with lamotrigine predominantly effective against depression and lithium predominantly effective against mania.     

Anticonvulsants and antipsychotics in the treatment of bipolar disorder

Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam) and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics.     

The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) who have rapid cycling features are often treatment refractory. Clear and conclusive evidence regarding effective treatments for this group is not available. METHODS: Patients with diagnoses of refractory bipolar disorder who were currently experiencing manic, mixed, depressive, or hypomanic episodes were treated with lamotrigine as add-on therapy (60 patients) or monotherapy (15 patients). We compared the efficacy of lamotrigine in the 41 rapid cycling and 34 non-rapid cycling patients with BD. RESULTS: Improvement from baseline to last visit was significant among both rapid cycling and non-rapid cycling patients for both depressive and manic symptomatology. For patients entering the study in a depressive episode, improvement in depressive symptomatology was equivalent in the two groups. Among patients entering the study in a manic, mixed, or hypomanic episode, those with rapid cycling improved less in manic symptomatology than did non-rapid cycling patients. Among rapid cycling patients with initial mild-to-moderate manic symptom severity, improvement was comparable to that in non-rapid cycling subjects; however, the subset of rapid cycling patients with severe initial manic symptomatology had little improvement in mania. Rapid cycling patients had earlier onset and more lifetime episodes of mania, depression, and mixed mania. CONCLUSIONS: Lamotrigine was generally effective and well tolerated in this group of previously non-responsive, rapid cycling bipolar patients.     

An open longitudinal study of patients with bipolar rapid cycling treated with lithium or lamotrigine for mood stabilization

Objectives: Patients with rapid cycling bipolar disorder are frequently observed to fail conventional treatment. We conducted a preliminary study to explore the potential efficacy of lamotrigine in the treatment of this refractory patient population.

Methods: In an open longitudinal investigation, 14 patients with rapid cycling bipolar disorder were treated for 1 year with either lithium or lamotrigine as mood stabilizer.

Results: Out of the seven patients with lithium, three out of seven (43%) had less than four and four out of seven (57%) had four or more episodes. In the lamotrigine group, six out of seven (86%) had less than four and one out of seven (14%) had more than four affective episodes (depressive, manic, hypomanic or mixed). In fact, three out of seven (43%) of the patients who were on lamotrigine therapy were without any further affective episodes. There was no evidence of a preferential antidepressant versus antimanic efficacy.

Conclusions: Although the study is limited by the small number of patients, the results are in line with other investigations, suggesting efficacy for lamotrigine and a suboptimal response for lithium in rapid cycling bipolar disorder. These preliminary data need to be confirmed with controlled double blind studies.     

Antiepileptic drugs and mood stability.

This paper will discuss different definitions of the term "mood stabilizer" and highlight in detail the antiepileptic drugs carbamazepine, valproate and lamotrigine with respect to their relative strengths in stabilizing mood in bipolar patients. These drugs are heterogeneous in their mechanisms of action and in their efficacy to stabilize patients with epilepsy and the various mood states in bipolar disorder. Lamotrigine has obtained approval in several countries for the indication of preventing bipolar depressive episodes, which raises the question of differential efficacy of other antiepileptic drugs as mood stabilizers in the prevention of either depressive or hypo-/manic episodes. A Medline Search to 2006 was conducted for controlled acute and maintenance studies of the three scientifically and clinically most established antiepileptic drugs carbamazepine, valproate and lamotrigine. The medications discussed in this review only partly fulfill definitions of a mood stabilizer, and we suggest that future research should focus on combined treatment strategies.     

A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder

BACKGROUND: Two clinical trials, prospectively designed for combined analysis, compared placebo, lithium, and lamotrigine for treatment of bipolar I disorder in recently depressed or manic patients. METHOD: 1315 bipolar I patients (DSM-IV) enrolled in the initial open-label phase, and 638 were stabilized and randomly assigned to 18 months of double-blind monotherapy with lamotrigine (N = 280; 50-400 mg/day fixed dose or 100-400 mg/day flexible dose), lithium (N = 167; serum level of 0.8-1.1 mEq/L), or placebo (N = 191). The primary endpoint was time from randomization to intervention for a mood episode. Data were gathered from August 1997 to August 2001. RESULTS: Lamotrigine and lithium were superior to placebo for time to intervention for any mood episode (median survival: placebo, 86 days [95% CI = 58 to 121]; lithium, 184 days [95% CI = 119 to not calculable]; lamotrigine, 197 days [95% CI = 144 to 388]). Lamotrigine was superior to placebo for time to intervention for depression (median survival: placebo, 270 days [95% CI = 138 to not calculable]; lithium, median not calculable; lamotrigine, median not calculable). Lithium and lamotrigine were superior to placebo for time to intervention for mania (median survival not calculable for any group). Results of additional analyses adjusted for index mood were similar; however, only lithium was superior to placebo for intervention for mania. There was no evidence that either active treatment caused affective switch. Adverse event analysis indicated more diarrhea (19% vs. 7%, p <.05) and tremor (15% vs. 4%, p <.05) in lithium-treated patients compared with lamotrigine-treated patients. CONCLUSIONS: Lamotrigine and lithium stabilized mood by delaying the time to treatment for a mood episode. Lamotrigine was effective against depression and mania, with more robust activity against depression. Lithium was effective against mania.     

New data on the use of lithium, divalproate, and lamotrigine in rapid cycling bipolar disorder.

The rapid cycling variant of bipolar disorder is defined as the occurrence of four periods of either manic or depressive illness within 12 months. Patients suffering from this variant of bipolar disorder have an unmet need for effective treatment. This review examines two major studies in an attempt to update understanding of the current therapies available to treat rapid cycling patients. The first trial compares lamotrigine versus placebo in 182 patients studied for 6 months. The second is a recently completed, 20-month trial comparing divalproate and lithium in 60 patients. Both trials had a double-blind, randomized parallel-group design. The data from the latter study indicate that there are no large differences in efficacy between lithium and divalproate in the long-term treatment of rapid cycling bipolar disorder. In addition, lamotrigine has the potential to complement the spectrum of lithium and divalproate through its greater efficacy for depressive symptoms.