FDA批准奥氮平与锂剂或丙戊酸盐合用于治疗双相情感障碍的急性躁狂发作

近期,FDA批准礼来公司的奥氮平 (olanzapine,Zyprexa) 与锂剂或丙戊酸盐 (Depakote,雅培公司)合用于治疗双相情感障碍的急性躁狂发作。本品是第一个获许可与其他心境稳定剂合用于治疗急性双相性躁狂的药物。本品于2000年获FDA许可单用于双相情感障碍相关急性躁狂发作的短期治疗,是唯一获FDA许可用于治疗此病的非典型抗精神病药。FDA的此项批准基于两项随机双盲安慰剂对照研究。研究显示,与单用锂剂或丙戊酸盐相比,合用本品治疗双相情感障碍患者的躁狂或混合型发作,能有效改善躁狂和抑郁症状。本品3年前获许可用于急性双相性躁狂的短期…     

心境稳定剂在治疗双相情感障碍抑郁发作中的临床疗效研究

目的探讨心境稳定剂在治疗双相情感障碍抑郁发作中的临床疗效。方法采用回顾性分析的方法对我院2015年1月至2016年9月于我院收治的100例双相情感障碍抑郁发作的患者的病历资料进行分析。随机分为两组:实验组和对照组,每组患者50例。实验组双相情感障碍抑郁发作的患者采用心境稳定剂联合抗抑郁药物治疗的方法进行治疗,而对照组双相情感障碍抑郁发作的患者则采用单用抗抑郁药物治疗的方法进行治疗。两组患者在治疗前后采用汉密尔顿抑郁量表及汉密尔顿焦虑量表进行评定给分。结果对照组双相情感障碍抑郁发作的患者在治疗后的总有效率为68%,实验组患者在治疗后的总有效率远高于对照组为92%,两组间比较(P<0.05),差异具有统计学意义。结论在临床中双相情感障碍抑郁发作的患者采用心境稳定剂联合抗抑郁药物进行治疗后,患者的临床症状有了很明显的改善,该方法值得临床推广和使用。     

心境稳定剂在治疗儿童精神障碍中的应用

心境稳定剂在儿童和青少年心理和行为障碍治疗中的应用广泛,适用于治疗双相情感障碍、破坏性行为障碍和注意力缺陷-多动障碍等行为障碍患者出现的冲动和攻击行为以及情绪不稳定和易激惹等表现,同时对发育迟缓儿童如精神发育迟滞和孤独症等患者出现的伤害他人或自伤行为治疗也有效果。在经典的心境稳定剂中,锂盐是唯一获准可一线用于儿童和青少年双相情感障碍患者躁狂发作和维持治疗的药物,而丙戊酸盐、卡马西平、奥卡西平和拉莫三嗪在治疗儿童攻击性或破坏性行为中也有一定的临床应用。选用心境稳定剂治疗儿童精神障碍时应考虑药物的疗效证据、安全性和不良反应以及患者的靶症状、疾病史、用药史和家族史等,以确保儿童用药安全、有效。     

双相情感障碍联合治疗研究进展与临床评价

目的 :研究双相情感障碍联合治疗的进展 ,评价其疗效与安全性 ,以期为临床合理应用提供参考。方法 :查阅近期相关国内、外文献 ,对涉及各临床时期的双相情感障碍联合治疗研究进展和临床评价进行介绍。结果与结论 :目前的研究结果提示 ,对于急性躁狂患者 ,非典型抗精神病药与心境稳定剂联用可明显提高疗效 ,且起效更迅速。对于双相抑郁患者 ,在心境稳定剂的基础上 ,加用帕罗西汀等新型抗抑郁药可改善疗效 ,且不增加转相的风险 ;关于维持治疗中的联合用药问题 ,锂盐和三环类抗抑郁药(TCA)长期联用并无优越性 ,且TCA会诱发躁狂。而心境稳定剂与新型抗抑郁药联用的长期随机对照研究仍很缺乏 ,还需要更多的研究来考察其疗效与安全性     

非典型抗精神病药物在双相障碍治疗中的应用

非典型抗精神病药物由于其自身独特的药理学特性,除了用于治疗精神分裂症外,其对双相障碍的疗效日益受到关注。目前较为明确的是,无论是单一用药还是与心境稳定剂联用,多数非典型抗精神病药用于控制双相障碍的急性躁狂发作均安全有效;其中奥氮平和喹硫平对双相障碍抑郁发作的疗效也得到了肯定。除此之外,有关非典型抗精神病药用于混合发作的治疗、稳定期的维持治疗、预防复发以及一些特殊类型如快速循环型双相障碍的治疗等的探索研究也在不断深入进行中。     

河北省双相障碍患者药物治疗现状的调查分析

目的:为促进河北省双相障碍患者治疗的规范化、合理化,特别是为提高基层的临床治疗水平提供参考。方法:选取在河北省39家精神专科医院或综合医院精神科接受精神药物治疗的门诊或住院双相障碍患者,通过问卷调查患者的药物治疗情况,并对数据进行统计分析。结果:共发放问卷521份,回收有效问卷519份,有效回收率为99.6%。397例(76.5%)患者接受心境稳定剂治疗,使用频率排前3位的分别为丙戊酸钠、碳酸锂和丙戊酸镁;455例(87.7%)患者接受抗精神病药治疗,使用频率排前5位的分别为喹硫平、奥氮平、利培酮、氯氮平和阿立哌唑;89例(17.1%)患者接受抗抑郁药治疗,其中73.0%使用选择性5-羟色胺再摄取抑制剂;154例(29.7%)患者接受苯二氮类药物治疗,47例(9.1%)患者辅以抗胆碱药物治疗,27例(5.2%)患者辅以β受体阻滞药治疗。双相障碍治疗以联合用药为主,428例(82.5%)患者联合2种以上精神药物治疗,以心境稳定剂联合抗精神病药为主;且抗抑郁药使用以联合心境稳定剂或抗精神病药为主。住院患者心境稳定剂的使用与门诊患者比较,差异有统计学意义(P<0.01),丙戊酸钠的使用频率低于门诊患者,碳酸锂和丙戊酸镁的使用频率高于门诊患者;住院患者接受抗抑郁药治疗的比例显著低于门诊患者,二者比较差异有统计学意义(P<0.05)。结论:河北省双相障碍患者的治疗以心境稳定剂联合抗精神病药为主要的方式;抗精神病药的使用比例较高,以非典型抗精神病药为主;抗抑郁药的使用以联合用药为主;心境稳定剂在住院与门诊的选择有所不同,且抗抑郁药门诊使用比例较高。双相障碍患者的治疗总体符合双相障碍防治指南的推荐用药原则。     

基于格林模式的服药管理干预结合丙戊酸盐对成人双相情感障碍患者情绪症状及疗效的影响

目的 探究基于格林模式的服药管理干预结合丙戊酸盐对成人双相情感障碍患者情绪症状及疗效的影响。方法选取本院2022年1月至2023年6月收治的80例双相情感障碍患者,按照随机数字表法分为研究组和对照组,各40例。对照组用丙戊酸盐治疗,观察组在对照组的基础上结合格林模式下的服药管理干预。比较两组患者临床疗效、狂躁症状[贝克-拉范森躁狂量表(BRMS)评分]、心理压力[抑郁自评量表（SDS）及焦虑量表（SAS）]、炎症因子、依从性。结果 治疗后,观察组治疗总效率及依从性高于对照组,差异有统计学意义（P<0.05）;观察组BRMS、SDS、SAS评分及IL-1β、TNF-α较对照组低,差异有统计学意义（P<0.05）;IL-2两组比较差异无统计学意义（P>0.05）。结论 结合格林模式的服药管理干预和丙戊酸盐治疗能有效增强双相情感障碍患者的疗效及治疗依从性,且对情绪症状的缓解更为显著。     

丙戊酸镁联合富马酸奎硫平治疗快速循环型双相情感障碍的效果观察

目的 探讨丙戊酸镁缓释片联合富马酸奎硫平治疗快速循环型双相情感障碍的效果.方法 42例随机分为治疗组和对照组,每组21例.治疗组给予丙戊酸镁缓释片联合富马酸奎硫平治疗,对照组给予单用丙戊酸镁缓释片治疗,均治疗2个月后评定临床疗效,随访2年,观察复发情况.结果 治疗组总有效率高于对照组,治疗后治疗组EI评分显著高于对照组,治疗组复发率明显低于对照组,差异有统计学意义(P<0.05,P<0.01).结论 丙戊酸镁缓释片联合富马酸奎硫平治疗快速循环型双相情感障碍效果明显,复发率低.     

心境稳定剂临床应用中常见不良反应

心境稳定剂 (ｍｏｏｄｓｔａｂｉｌｉｚｅｒｓ) ,有时也被译为心境 (情感、情绪 )调整剂 ,或称情感稳定性药物 (ｍｏｏｄ/ａｆｆｅｃｔｉｖｅｓｔａｂｉｌｉｚｉｎｇｄｒｕｇｓ/ａｇｅｎｔｓ)。心境稳定剂原称“抗躁狂药”(ａｎｔｉｍａｎｉｃｄｒｕｇｓ) ,近年来的“改名”突出了此类药物对双相情感障碍躁狂及抑郁症状均有效 ,而不仅仅是抗躁狂作用。本文就心境稳定剂临床应用中常见的不良反应作简要综述。1　种类一般认为 ,某种药物只需具备对躁狂及抑郁双相均有治疗 /预防作用即可归入此类。此类药物中 ,锂盐和卡马西平不良反应较多 ;新…     

双相抑郁发作的治疗:情感稳定剂或抗抑郁剂

治疗双相情感障碍常使用某种情感稳定剂,当抑郁发作时,临床常追加另一种情感稳定剂,或抗抑郁剂。本文就此作一双盲对比研究。２７例门诊病人,符合ＤＳＭ－Ⅳ诊断标准,其时发生抑郁发作,排除精神病性和快速循环型双相障碍。病人半年内无酒精或药物滥用,无急性躯体疾病。入选者均应用一种情感稳定剂达３个月以上,如１９例使用碳酸锂的剂量为一日１２００±２４０ｍｇ,血药浓度为０．８±０．２ｍｍｏｌ／Ｌ;８例服用丙戊酸钠的剂量为一日１２００±２１０ ｍｇ,血药浓度为５７０±７１ｍｍｏｌ／Ｌ。除５例服用催眠药水合氯醛或佐…     

Acute and maintenance treatment with mood stabilizers

Treatment of bipolar disorder is complicated by the multiple phases of the illness, dimensional symptomatology that varies considerably across individuals, and a limited spectrum of activity for all mood stabilizers. Randomized, blinded, placebo-controlled studies provide clear guidelines to the overall efficacy of treatments for mania. However, for secondary questions, such as the treatment to employ when lithium or valproate is inadequate as monotherapy, evidence is incomplete, and usually derived from both smaller and less well-designed studies. For mania, the spectrum of efficacy of valproate is broader than for other mood stabilizers. However, many patients obtain inadequate benefit from monotherapy regimens of all mood stabilizers. Recent studies indicate that for patients who develop mania while taking a mood stabilizer, combinations of an antipsychotic and a mood stabilizer yield greater improvement than does continuation of the mood stabilizer alone. Maintenance-treatment studies support the efficacy of lithium, valproate and lamotrigine, although with a different spectrum of benefits and limitations for each. Valproate and lithium provide greater benefits for prevention of manic relapses and control of manic symptomatology than for depression. Several studies indicate actual worsening in depressive aspects of bipolar disorder with lithium treatment. Lamotrigine appears effective in delaying relapse into a new episode, with most benefits limited to delaying time to depression. Lamotrigine has not shown anti-manic activity in placebo-controlled studies. In contrast to traditional antidepressant medications, lamotrigine has not been associated with induction of mania, or of rapid-cycling illness symptomatology. Recent studies reported that carbamazepine was inferior to valproate in acute mania, and inferior to lithium in maintenance treatment. Other putative mood stabilizers have to date yielded negative or inconclusive results in studies in mania. Systematic studies are needed to clarify treatment guidelines for youth with bipolar disorder, and for other special populations, e.g. pregnant women and the elderly.     

The armamentarium of treatments for bipolar disorder: a review of the literature

To assess current pharmacotherapeutic options for bipolar disorder, with particular emphasis on the use of antipsychotic agents, Medline and EMBASE were searched between January 1980 and December 2005 using the keywords "schizoaffective disorder" and "bipolar disorder", combined with various antidepressants, antipsychotics, lithium or other mood stabilizers. English-language articles, review articles and original research articles were reviewed. Most data are available for the "mood stabilizers" lithium and valproate. However, these agents have important limitations regarding their tolerability and efficacy in certain groups. Newer anticonvulsants, especially lamotrigine, have demonstrated efficacy across mood-symptom domains. Antidepressants are not generally favoured as monotherapy in patients with bipolar depression or schizoaffective disorder, due to their potential to induce switching to manic states. However, data are emerging for the efficacy of selective serotonin reuptake inhibitors for bipolar depression in combination with atypical antipsychotics. Atypical antipsychotics may also be used as monotherapy or in conjunction with mood stabilizers for the treatment of acute mania and for continuing maintenance therapy. The choice of antipsychotic may be influenced by the therapeutic situation; formulations that facilitate administration in the acute scenario can provide rapid tranquillization, whereas those that enhance compliance may have a place in maintenance therapy. Our results suggest a growing role for atypical antipsychotics in the treatment of bipolar disorder and further data are anticipated.     

Effects of mood stabilizers on the disruption of prepulse inhibition induced by apomorphine or dizocilpine in mice

The prepulse inhibition of the startle response provides an operational measure of sensorimotor gating in which a weak stimulus presented prior to a startling stimulus reduces the startle response. Prepulse inhibition deficits were observed in patients with several neuropsychiatric disorders, including schizophrenia and acute manic bipolar patients. Valproic acid, carbamazepine and lithium carbonate are frequently used as mood stabilizers in patients with bipolar affective disorder and schizophrenia. However, little is known about the mechanisms of action of mood stabilizers on prepulse inhibition deficits. In this study, we investigated the effects of mood stabilizers on the disruption of prepulse inhibition of the acoustic startle response induced by either apomorphine or dizocilpine in mice. Valproate (30-300 mg/kg, i.p.), carbamazepine (3-30 mg/kg, i.p.) and lithium carbonate (10-100 mg/kg, p.o.) had any effect on prepulse inhibition by itself. Valproate, carbamazepine and lithium carbonate reversed the disruption of prepulse inhibition induced by apomorphine (1 mg/kg, s.c.). Although valproate and carbamazepine had no effect on the disruption of prepulse inhibition induced by dizocilpine (0.3 mg/kg, s.c.), lithium carbonate exacerbated the dizocilpine-induced disruption. These results suggest that valproate, carbamazepine and lithium carbonate reverse the disruption of prepulse inhibition through the dopaminergic system.     

Treatment of bipolar affective disorder in clinical practice

A case note survey of 100 outpatients with a clinical diagnosis of bipolar affective disorder in a UK inner city teaching hospital revealed monotherapy with a mood stabilizer in only 23% of patients, mostly lithium (15%). Overall, 51% of patients were prescribed lithium, 19% carbamazepine and 5% valproate with only 8% receiving a combination of two mood stabilizers. Treatment appeared to be inadequate in 13/51 of patients on lithium, 9/19 of those on carbamazepine and 1/5 of those on valproate. Antipsychotics were used as monotherapy in 20% of patients and combined with a mood stabilizer in 43% of patients. Only 6% of patients were on atypical antipsychotics. These findings suggest that the treatment for many patients does not match recommendations. Clearer evidence on the place of combination mood stabilizers and adjunctive antipsychotics, particularly atypicals is needed in the treatment of bipolar affective disorder.     

Anticonvulsants in the treatment of mood disorders: assessing current and future roles

Anticonvulsants are frequently used in the treatment of affective illnesses, especially for patients refractory to or intolerant of other treatments. The differential therapeutic roles of anticonvulsants, however, remain largely undetermined. The author reviews the available efficacy data for carbamazepine, oxcarbazepine, valproate, lamotrigine, gabapentin and topiramate. Valproate is efficacious in the monotherapy of acute manic presentations but confirmatory evidence of the efficacy of valproate in long-term maintenance has been elusive. Valproate and possibly carbamazepine, may provide a therapeutic advantage over lithium in non-classic bipolar conditions such as mixed mood states and rapid cycling conditions. Lamotrigine is unique among the anticonvulsants in its monotherapy efficacy for bipolar I depression. Emerging data also suggest a role for lamotrigine in the adjunctive treatment of depressive mixed states and rapid cycling conditions in the absence of prominent manic symptoms. Controlled trials have found gabapentin ineffective for acute mania and refractory bipolar conditions. The role of gabapentin in the treatment of other aspects of affective illness remains uncertain. Definitive statements regarding the differential psychotropic use of topiramate and oxcarbazepine are not possible, though active investigation is underway to better characterise the utility of topiramate. The author suggests that current diagnostic models utilised in controlled trials may limit identification of differential therapeutic benefits. Caution is advised in generalising from the ability or inability of an agent to demonstrate antimanic activity. Future studies of newer anticonvulsants should include dimensional perspectives and soft bipolar presentations, as the greatest contribution of the newer anticonvulsants may be in treatment of mood conditions other than acute mania.     

Mood stabilizers and atypical antipsychotics: bimodal treatments for bipolar disorder

Treatment options for bipolar disorder have rapidly expanded over the last decade, but providing optimal management remains an elusive goal. The authors reviewed the literature on the efficacy of agents with the best clinical evidence supporting their use in bipolar disorder, including the mood stabilizers lithium, valproate, lamotrigine, and carbamazepine, as well as the atypical antipsychotics olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Most medications appear to be more effective for symptoms of mood elevation than for symptoms of depression. The efficacy, tolerability, and safety profiles of agents must be considered when making clinical decisions. Several agents, including lithium, valproate, olanzapine, quetiapine, and risperidone, can cause problematic weight gain. In addition, the use of atypical antipsychotics has been associated with an increased risk of metabolic abnormalities such as dyslipidemia, hypergylycemia, and diabetes mellitus. In most patients, monotherapy offers inadequate efficacy. Further investigation of combinations of agents such as mood stabilizers and atypical antipsychotics may yield valuable insights into the potential of combination therapies to enhance clinical outcomes in patients with bipolar disorder.     

Anticonvulsants in the treatment of mood disorders: assessing current and future roles

Anticonvulsants are frequently used in the treatment of affective illnesses, especially for patients refractory to or intolerant of other treatments. The differential therapeutic roles of anticonvulsants, however, remain largely undetermined. The author reviews the available efficacy data for carbamazepine, oxcarbazepine, valproate, lamotrigine, gabapentin and topiramate. Valproate is efficacious in the monotherapy of acute manic presentations but confirmatory evidence of the efficacy of valproate in long-term maintenance has been elusive. Valproate and possibly carbamazepine, may provide a therapeutic advantage over lithium in non-classic bipolar conditions such as mixed mood states and rapid cycling conditions. Lamotrigine is unique among the anticonvulsants in its monotherapy efficacy for bipolar I depression. Emerging data also suggest a role for lamotrigine in the adjunctive treatment of depressive mixed states and rapid cycling conditions in the absence of prominent manic symptoms. Controlled trials have found gabapentin ineffective for acute mania and refractory bipolar conditions. The role of gabapentin in the treatment of other aspects of affective illness remains uncertain. Definitive statements regarding the differential psychotropic use of topiramate and oxcarbazepine are not possible, though active investigation is underway to better characterise the utility of topiramate. The author suggests that current diagnostic models utilised in controlled trials may limit identification of differential therapeutic benefits. Caution is advised in generalising from the ability or inability of an agent to demonstrate antimanic activity. Future studies of newer anticonvulsants should include dimensional perspectives and soft bipolar presentations, as the greatest contribution of the newer anticonvulsants may be in treatment of mood conditions other than acute mania.     

Mood stabilization in the treatment of bipolar disorder: focus on quetiapine

The use of at least one mood-stabilizing agent is common clinical practice in the treatment of bipolar disorder, regardless of the treatment setting or disease phase. However, a consensus definition of 'mood stabilizer' remains to be established. A mood stabilizer has been operationally described as an agent that is useful in at least one phase of bipolar disorder while not worsening any other phase of the illness. More stringent definitions have been proposed, and it can be argued that a clinically effective mood stabilizer would have efficacy in a broad range of affective, psychotic, behavioral and cognitive domains in all phases of bipolar disorder and would be well tolerated across a range of doses for sustained periods. Clinically effective mood stabilizers should treat mania and depression, while preventing recurrence and improving quality of life. Effective treatment should not precipitate mania, depression, or rapid cycling, and should minimize the burden of treatment-emergent side effects. Data from clinical studies of quetiapine are reviewed in context with the literature discussing traditional and emerging mood stabilizers. Using a liberal definition, the evidence for quetiapine qualifies it as a bimodal mood stabilizer based on its demonstrated effectiveness in the treatment of bipolar mania and depression. Further data suggest that quetiapine has promise across all phases of bipolar disorder with the potential to meet even the most stringent definitions of a mood stabilizer.     

Levetiracetam in the treatment of rapid cycling bipolar disorder

Levetiracetam (LEV) is a novel anticonvulsant that is currently investigated in bipolar disorder. It may be useful in the treatment of refractory and complicated cases, in which conventional mood stabilizers are not effective. We report two cases of rapid cycling bipolar disorder in which the add-on of LEV to a conventional treatment regimen improved symptoms of depression, as well as those of mania/mixed mania, and disrupted the severe rapid cycling pattern.