拉莫三嗪治疗双相情感障碍抑郁发作的临床观察

目的:探究在双相情感障碍抑郁发作中应用拉莫三嗪的临床效果。方法:在我院2017年1月至2017年10月收治的120例处于急性抑郁发作的双相情感障患者中,选择60例作为对照组,治疗过程中服用碳酸锂;另选择60例作为研究组,在对照组的基础上联用拉莫三嗪。统计治疗前后两组患者的汉密尔顿抑郁量表(HAMD)评分差异。结果:经过治疗,研究组患者的HAMD评分显著低于对照组(P0.05)。结论:拉莫三嗪可有效改善双相情感障碍抑郁发作的患者的抑郁症状,具有较高的临床应用价值     

警惕拉莫三嗪引发无菌性脑膜炎

2010年8月12日,FDA发布了关于拉莫三嗪（Lamotaigine）可致无菌性脑膜炎的安全信息,以提醒医生和患者引起警惕。拉莫三嗪属于抗癫痫药,临床用于治疗2岁以上儿童的癫痫以及成人双相情感障碍。     

FDA批准拉莫三嗪口腔速崩片上市

FDA批准葛兰素史克公司的拉莫三嗪口腔速崩片（Lamictal ODT）上市,其剂量规格为每片含拉莫三嗪25、50、100和200mg。本品由葛兰素史克公司和Eurand公司合作开发,是迄今惟一获准上市的癫痫治疗药口腔速崩片。本品的上市为吞咽固体制剂困难者以及癫痫或双相情感障碍患者提供了方便。     

FDA批准拉莫三嗪用于治疗双相情感障碍

2003年6月,美国FDA批准葛兰素史克公司的拉莫三嗪(lamotrigine, Lamictal) 片剂用于治疗成人急性躁狂发作,本品也可作为双相情感障碍患者的长期维持治疗药物,以延迟情绪异常的发作 (抑郁、躁狂及混合型发作)。本品是自锂剂用于双相情感障碍的维持治疗以来,FDA批准的第一个用于该适应证的长期治疗药物。FDA此次批准基于两项为期18个月的随机安慰剂对照临床研究,研究共涉及1305例躁狂或抑郁成人患者,是迄今有关双相情感障碍治疗规模最大的临床研究。在标签公开期后,病情达到稳定标准的患者进入随机期。研究结果显示,本品能明显推迟双相情…     

拉莫三嗪与喹硫平治疗双相抑郁的对照研究

目的比较拉莫三嗪(利必通)和喹硫平(思瑞康)治疗双相抑郁的疗效及安全性。方法对71例符合CCMD-3诊断双相障碍(目前为抑郁发作)的患者按随机、平行、对照的方法分为拉莫三嗪组和喹硫平组,观察8周,分别于第0、2、4、6、8周末用HAMD、CGI评价疗效,于第2、4、6、8周末用TESS评定不良反应,于第4、8周末用BRMS评定躁狂症状。结果拉莫三嗪组的痊愈率34.21%,有效率65.79%,喹硫平组的痊愈率39.39%,有效率69.70%。两组疗效比较无显著性差异(P>0.05),两组不良反应发生率相当。结论拉莫三嗪和喹硫平均可首选用于双相抑郁治疗,且安全性、不良反应相当。     

拉莫三嗪联合帕罗西汀治疗双相抑郁的临床疗效及安全性

目的:探讨拉莫三嗪联合帕罗西汀治疗双相抑郁的临床疗效及安全性。方法:将118例双相抑郁患者随机分入对照组(58例)与观察组(60例),给予对照组患者帕罗西汀口服治疗,观察组患者接受拉莫三嗪联合帕罗西汀口服,疗程8周。治疗前后采用汉密尔顿抑郁量表(HAMD)及临床总体印象量表(CGI)评估疗效。结果:治疗后8周,观察组治疗有效率显著高于对照组(88.3%(53/60)对70.7%(41/58),P<0.05);观察组HAMD认知障碍、焦虑/躯体化、阻滞以及睡眠障碍因子显著优于对照组(P<0.05);观察组CGI评分显著低于对照组(P<0.05);两组不良反应无显著性差别。结论:拉莫三嗪联合帕罗西汀治疗双相抑郁临床疗效确切,且不增加不良反应。     

双相抑郁障碍的诊断及治疗

双相抑郁障碍患病率高,且临床上易误诊和漏诊,导致不正确、不合理的药物治疗.因此,早期诊断及合理的治疗策略非常重要.本文对双相抑郁障碍的自身特点、相关特征和药物治疗(锂盐、拉莫三嗪、非典型抗精神病药物、抗抑郁药)作一综述,以供临床工作者参考.     

拉莫三嗪与丙戊酸钠治疗双相抑郁效果比较

目的：分析拉莫三嗪与丙戊酸钠治疗双相抑郁的疗效及安全性。方法选择在本院接受治疗的双相抑郁的患者作为研究对象,根据不同治疗方法分为观察组和对照组各46例,其中观察组给予拉莫三嗪治疗,对照组给予丙戊酸钠治疗,比较两组患者的治疗后耶鲁-布朗强迫症量表（Y-BOCS）及汉密尔顿抑郁量表评分（HAMD）、治疗效果、不良反应、复发率等指标。结果观察组痊愈率、总有效率均明显高于对照组;Y-BOCS及HAMD评分、不良反应发生率,以及治疗后半年、1年、3年复发率均明显低于对照组,差异有统计学意义。结论拉莫三嗪用于双相抑郁患者治疗可以有效减轻抑郁程度,减少不良反应发生,降低治疗后的远期复发率,结论值得进一步研究。     

拉莫三嗪联合舍曲林治疗双相抑郁的临床观察

目的:探讨拉莫三嗪联合舍曲林治疗双相抑郁的抗抑郁、延缓抑郁复发及其对预防转躁的影响。方法:将60例双相抑郁患者分为研究组(拉莫三嗪联合舍曲林组)和对照组(舍曲林组),观察2组在抗抑郁、延缓抑郁复发、预防转躁方面的疗效以及药物不良反应(ADR),1年后随访。结果:研究组在抗抑郁、延缓抑郁复发方面明显优于对照组,且转躁率低,ADR少。结论:拉莫三嗪联合舍曲林可有效用于双相抑郁治疗,安全性较好。     

拉莫三嗪在美国被批准替换丙戊酸

葛兰素史克公司的抗癫痫药物利必通 (Lamictal,拉莫三嗪 )已被美国食品和药品管理局 (FDA)批准追加适应证。拉莫三嗪从原来与丙戊酸联合使用可改为单一使用 ,用以治疗≥ 16岁局限性癫痫患者。 2 0 0 3年 1月 ,FDA批准拉莫三嗪用于辅助治疗≥ 2岁儿童患者的局限性癫痫发作。 2 0 0 3年6月 ,拉莫三嗪被批准用于维持治疗双相精神障碍。最近这次批准的拉莫三嗪新适应证的依据是 77例癫痫患者为期 18周的研究结果。在整个研究期间 ,拉莫三嗪和丙戊酸的血药浓度在规定间期内受到监控 ,患者由联合用药改为单独使用拉莫三嗪后 ,其血液浓度仍能维…     

Safety and tolerability of lamotrigine for bipolar disorder.

Tolerability and safety are important considerations in optimising pharmacotherapy for bipolar disorder. This paper reviews the tolerability and safety of lamotrigine, an anticonvulsant recommended in the 2002 American Psychiatric Association guidelines as a first-line treatment for acute depression in bipolar disorder and one of several options for maintenance therapy. This paper reviews the tolerability and safety of lamotrigine using data available from a large programme of eight placebo-controlled clinical trials of lamotrigine enrolling a total of nearly 1800 patients with bipolar disorder. This review is the first to collate all the safety information from these clinical trials, including data from four unpublished studies. The results these trials in which 827 patients with bipolar disorder were given lamotrigine as monotherapy or adjunctive therapy for up to 18 months for a total of 280 patient-years of exposure demonstrated that lamotrigine is well-tolerated with an adverse-event profile generally comparable with that of placebo. The most common adverse event with lamotrigine was headache. Lamotrigine did not appear to destabilise mood and was not associated with sexual adverse effects, weight gain, or withdrawal symptoms. Few patients experienced serious adverse events with lamotrigine, and the incidence of withdrawals because of adverse events was low. Serious rash occurred rarely (0.1% incidence) in the clinical development programme including both controlled and uncontrolled clinical trials. These findings - considered in the context of data showing lamotrigine to be effective for bipolar depression - establish lamotrigine as a well-tolerated addition to the psychotropic armamentarium.     

Gabapentin and lamotrigine in bipolar disorder.

The utility of gabapentin and lamotrigine for the treatment of bipolar disorder is reviewed. Bipolar disorder is characterized by extreme mood fluctuations, including mania, hypomania, depression, and mixed episodes. Extrapolation of postulated mechanisms of anticonvulsant activity in bipolar disorder has led to the use of the newer anticonvulsants gabapentin and lamotrigine for therapy. Both agents appear promising on the basis of limited (often anecdotal) evidence. They may prove effective in patients with difficult cases of bipolar disorder, such as patients with rapid cycling, mixed episodes, and illness refractory to other treatments. Lamotrigine may offer a much-needed treatment alternative for bipolar depression and could be found effective for acute mania, but the need for slow dosage adjustment and the risk of rash may limit overall clinical utility. Gabapentin may offer significant advantages for acute mania: The dosage can be adjusted rapidly, adverse effects are generally minimal, the therapeutic index is high, there is no required laboratory monitoring, and there is minimal potential for interactions with other psychotropics. Until the results of randomized controlled trials are known, however, these two agents should be reserved for patients with bipolar disorder unresponsive to traditional therapies and for patients who cannot tolerate traditional agents. Preliminary evidence indicates that gabapentin and lamotrigine may be useful for the treatment of bipolar disorder.     

An observational nationwide register based cohort study on lamotrigine versus lithium in bipolar disorder

It is not clear whether the effectiveness of lamotrigine versus lithium differs for patients with bipolar disorder treated in clinical practice. We compared rates of switch to, or add on of, another psychotropic, and rates of psychiatric hospitalization for patients treated with lamotrigine or lithium in clinical practice. Using linkage of nationwide Danish registers we identified 730 patients who received lamotrigine and 3518 patients received lithium subsequent to a diagnosis of bipolar disorder in psychiatric hospital settings during a period from 1995 to 2006. The overall rate of switch to or add on of another psychotropic (the opposite drug of interest (lithium or lamotrigine), antidepressants, antipsychotics or other anticonvulsants than lamotrigine) was increased for lamotrigine compared with lithium (HR?=?2.60, 95% CI: 2.23-3.04), regardless of whether the index episode was depressive, manic, mixed or remission. In addition, the overall rate of psychiatric hospitalization was increased for lamotrigine compared with lithium (HR?=?1.45, 95% CI: 1.28-1.65), as were the rates for patients with a depressive (HR?=?1.31, 95% CI: 1.01-1.70) and patients with a manic (HR?=?1.65, 95% CI: 1.31-2.09) index episode. Rates did not differ significantly between the drugs for patients with a mixed index episode and for patients in remission. It is concluded that in daily clinical practice, treatment with lithium is in general superior to treatment with lamotrigine.     

Lamotrigine: a review of its use in bipolar disorder

Lamotrigine (Lamictal), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane. Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months' duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure. Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania.Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine- than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain. The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine. CONCLUSION: Lamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.     

Lamotrigine in mood disorders

Lamotrigine is an anticonvulsant drug with good efficacy and safety in the treatment of epilepsy. There is now substantial evidence that lamotrigine is also useful in treating resistant depression, rapid cycling bipolar affective disorder, depressive episodes in bipolar affective disorder and in the maintenance phase or prophylaxis of bipolar affective disorder. There are possible roles in managing mood changes in borderline personality disorder, reducing chronic pain and treating schizoaffective disorder. The general range of doses found effective in affective disorders is from 50 to 300 mg daily. Clinical use seems to involve a titration of dose upwards over several weeks until the desired effect is obtained. However, further definitive double-blind, randomised controlled trials against gold standard treatments are required. Lamotrigine has a preferable side-effect profile compared to standard agents for bipolar affective disorder such as lithium or carbamazepine. Further research is certainly warranted and, given its tolerability, could point to lamotrigine as the treatment of choice for some affective disorders.     

Lamotrigine-induced toxic epidermal necrolysis in three patients treated for bipolar disorder

Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), is a mild-to-life-threatening process that has been described after exposure to many antiepileptic drugs. The increased use of antiepileptic drugs for treatment of bipolar disorder and neurologic disorders has extended the risk of exfoliative disorder to this population of patients, and these patients and their health care providers may not be familiar with the risks involved with these drugs. We describe the cases of a 28-year-old woman with bipolar 1 disorder initially treated with lamotrigine, and two adolescent girls with bipolar 2 disorder treated with lamotrigine after poor responses to other drug regimens. In all three patients, rashes progressed to toxic epidermal necrolysis in spite of treatment with corticosteroids at their local hospitals; thus, they were transferred to our burn treatment center. Response to early corticosteroid treatment in suppressing progression of exfoliation was variable in these patients. Ultimately, two of the three required ventilatory support; their conditions improved within 8-32 days of treatment, and they were discharged from the hospital. Case reports of lamotrigine-induced exfoliative disorder in patients with bipolar disorder have been published. However, these three patients were admitted to our burn treatment center within a 12-month period. Our institution admits approximately 10-12 patients with TEN/year, and the increased use of lamotrigine for treatment of bipolar disorder is likely to result in more patients with TEN. Therefore, health care professionals need to be aware of the early signs and symptoms of exfoliative dermatotoxicity when treating patients with lamotrigine.     

Spotlight on lamotrigine in bipolar disorder

Lamotrigine (Lamictal), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane. Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months' duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure. Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania. Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine- than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain. The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine. CONCLUSION: Lamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.     

Lamotrigine add-on therapy to venlafaxine treatment in adolescent-onset bipolar II disorder: a case report covering an 8-month observation period

Observations made with lamotrigine add-on therapy with venlafaxine in this case give clues for some aspects of its use in adolescent-onset bipolar II disorder. An 18-year-old adolescent boy with a 3-year history of bipolar II disorder had experienced 2 episodes of hypomania and 4 episodes of major depression. He had been depressed for the last 3 months and had taken olanzapine 5 mg daily for over 6 weeks as mood stabilizer but was still depressed at referral. Other aspects of the patient history included anhedonia, psychomotor retardation, poor concentration, a feeling of hopelessness, hypersomnia, overeating, weight gain, low energy and a refusal to attend school. Parents reported that his symptoms had recently become more severe. His medicine was replaced by venlafaxine, which has a more rapid onset of action and is often used in bipolar depression, especially in patients with atypical depression. Since the clinical response at 6 weeks was only partial, lamotrigine was added to this regimen. The patient responded to lamotrigine after 3 weeks of treatment while on a dose of 50 mg/ day. After 6 weeks of treatment, whilst on a dose of 75 mg/day, his symptoms remitted completely with no evidence of any adverse effects. At the time of publication of this article, the patient had remained euthymic for a total of 8 months. The present report shows that lamotrigine add-on therapy with venlafaxine facilitated clinical remission and that this combination is well tolerated.     

Lamotrigine in mood disorders

SUMMARY

Lamotrigine is an anticonvulsant drug with good efficacy and safety in the treatment of epilepsy. There is now substantial evidence that lamotrigine is also useful in treating resistant depression, rapid cycling bipolar affective disorder, depressive episodes in bipolar affective disorder and in the maintenance phase or prophylaxis of bipolar affective disorder. There are possible roles in managing mood changes in borderline personality disorder, reducing chronic pain and treating schizoaffective disorder.

The general range of doses found effective in affective disorders is from 50 to 300?mg daily.

Clinical use seems to involve a titration of dose upwards over several weeks until the desired ! effect is obtained.

However, further definitive double-blind, randomised controlled trials against gold standard treatments are required.

Lamotrigine has a preferable side-effect profile compared to standard agents for bipolar affective disorder such as lithium or carbamazepine. Further research is certainly warranted and, given its tolerability, could point to lamotrigine as the treatment of choice for some affective disorders.     

Rapid cycling bipolar disorder: clinical characteristics and treatment options

Approximately one of six patients who seek treatment for bipolar disorder present with a rapid cycling pattern. In comparison with other patients who have bipolar disorder, these individuals experience more affective morbidity in both the immediate and distant future and are more likely to experience recurrences despite treatment with lithium or anticonvulsants. Particular care should be given to distinguishing rapid cycling bipolar disorder from attention-deficit hyperactivity disorder in children or adolescents and from borderline personality disorder in adults. Perhaps four of five cases of rapid cycling resolve within a year, but the pattern may persist for many years in the remaining patients. As with bipolar disorder in general, depressive symptoms produce the most morbidity over time. Controlled studies have not established that antidepressants provoke switching or rapid cycling, but neither have they been shown consistently to have benefits in bipolar illness. Successful management will often require a sequence of trials with mood stabilizer drugs, beginning with lithium in treatment-naive patients. Efforts to minimise adverse effects, and the recognition that full benefits may not be apparent for several months, will make the premature abandonment of a potentially helpful treatment less likely. Placebo-controlled studies so far provide the most support for the use of lithium and lamotrigine as prophylactic agents. The combination of lithium and carbamazepine, valproate or lamotrigine for maintenance has some support from controlled studies, as does the adjunctive use of olanzapine.