心境稳定剂的药物相互作用

心境稳定剂在临床应用中普遍存在联合用药现象,不仅有多种心境稳定剂的合用,也有与抗精神病药、抗抑郁药的合用,还有心境稳定剂本身作为辅助用药等问题。目前广泛使用的心境稳定剂包括锂盐与抗癫痫药物,而多药联用就有可能在药物体内过程的各环节发生相互作用。本文将从药物在体内的分布、代谢与排泄等药动学过程及药效学方面来综述心境稳定剂与其他可能合用药物的相互作用,以期为临床合理选药提供参考。     

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…     

中山市住院流浪精神病患者用药现况调查

目的：了解中山市住院流浪精神病患者的用药情况。方法采用横断面调查方法,以2O13- O7-17为时间点,对中山市第三人民医院住院流浪精神病患者的用药情况进行调查。结果使用频率最高的抗精神病药物是利培酮,其次是氯氮平和奋乃静;使用一种抗精神病药物患者83例,两种抗精神病药物联用患者9例;使用心境稳定剂患者32例,抗精神病药物与心境稳定剂联用者26例;使用抗抑郁药患者1例;使用苯二氮卓艹类药物患者23例。结论中山市住院流浪精神病患者使用的抗精神病药物以第二代抗精神病药物为主,注重心境稳定剂、抗抑郁药及苯二氮卓艹类药物的使用,兼顾关注患者的躯体情况,从医疗用药方面体现了中山市对流浪精神病患者救治的重视。     

我院2008-2011年心境稳定剂使用分析

目的通过分析心境稳定剂的应用状况及变化趋势,为合理应用和科学管理此类药物提供参考依据。方法对我院2008-2011年心境稳定剂的应用品种、用药金额、用药频度(DDDs)、限定日费用、序号比值等进行统计分析。结果 4年间丙戊酸镁的用药金额一直占据首位,拉莫三嗪列第2位。自2010年起奥卡西平的使用金额明显增加,列第3位。按用药频度排序,碳酸锂一直位居第一位,丙戊酸钠和丙戊酸镁则分列2、3位。结论 4年中,心境稳定剂的用药金额、DDDs均逐年增加,碳酸锂和丙戊酸盐仍为大众最易接受的品种,本院心境稳定剂的应用基本合理。     

丙戊酸盐治疗双相情感障碍的研究进展

作为心境稳定剂,丙戊酸盐治疗各型双相情感障碍均有一定的疗效。近年来对各型双相情感障碍患者进行的临床研究证实：丙戊酸盐能改善躁狂症状;联合镇静药物治疗可有效改善抑郁症状;联合抗抑郁药物预防抑郁发作的疗效优于锂盐。丙戊酸盐与其他心境稳定剂联合治疗快速循环型双相情感障碍患者时可能更有益,也更适用于非快速循环型双相情感障碍患者的长程治疗。     

心境稳定剂研究进展及合理应用

心境稳定剂（Mood Stabilizers）是几类不同药物具有相同治疗作用的统称，它包括了抗躁狂药物碳酸锂，抗抽搐药物卡马西平、丙戊酸盐和不典型抗精神病药物奥氮平、利培酮、奎硫平等。     

新型抗精神病药物在双相情感性疾病中的应用

新型抗精神病药物在精神科临床应用 ,是近年来精神分裂症治疗学进展的重要标志。随着这些新型药物 (如利培酮、奥氮平、奎的平、寿廷多等 )临床应用经验的不断积累 ,人们已经注意到这些抗精神病药物的其他作用 ,对双相情感性疾病的治疗就是其中之一。人们在将这些药物应用于双相情感性疾病的过程中 ,逐渐认识到其类心境稳定剂样作用 ,这一重要的发现进一步促使了新型抗精神病药物在双相情感性精神障碍中的应用。1　抗躁狂效应作为非典型抗精神病药物的氯氮平 ,不论是单独应用 ,还是联合其他心境稳定剂 (如碳酸锂、丙戊酸钠、卡马西平 )都已…     

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。     

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。     

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。     

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.     

Combination of aripiprazole with mood stabilizers for the treatment of bipolar disorder: from acute mania to long-term maintenance

Introduction: Bipolar disorder is characterized by a complex set of symptoms, including recurrent manic, depressive or mixed episodes. Acute and long-term treatment of patients with bipolar disorder is mandatory to prevent symptom relapse and episode recurrences. Outcomes with monotherapy are often unsatisfactory in clinical practice, hence combinations of mood stabilizers and antipsychotics are widely utilized in patients showing no or partial response to, as well as intolerance to, monotherapies. This may offer a therapeutic advantage, however, the possibility of an increased incidence of side effects should be considered.

Areas covered: This paper reviews the current treatment guidelines for the treatment of bipolar disorder and examines the rationale behind the use of aripiprazole in combination with mood stabilizers for acute and long-term treatment of bipolar disorder.

Expert opinion: The combination of aripiprazole and mood stabilizers seems to offer an effective and relatively well-tolerated option for the treatment of acute mania and for the maintenance treatment of patients with bipolar I disorder. The combination presents a lower risk of metabolic side effects compared with other combination therapies, but increases the risk of extrapyramidal side effects with long-term treatment. The aripiprazole–valproate combination seems to be particularly promising in the treatment of patients with comorbidities such as anxiety and drug abuse, obsessive-compulsive disorder and bipolar disorder, as well as in mixed depressive disorder. Controlled trials are necessary in order to confirm these observations and to provide a useful insight for improving the use of drug combinations in bipolar patients.     

Adjunctive topiramate in the maintenance treatment of bipolar disorders: an open-label study

SUMMARY

Objective: A considerable number of patients with bipolar disorder fail to respond completely to mood stabilizers. The anti-epileptic topiramate shares some pharmacological actions with carbamazepine and valproate. We therefore explored the efficacy and tolerability of topiramate in the prophylaxis of bipolar disorder.

Methods: Fifty-six patients receiving outpatient treatment for bipolar affective disorder who had been on mood stabilizers, and had relapsed at least once in the past 12?months, were treated with topiramate in an add-on design and were evaluated for 1?year. Patients were assessed biweekly for the first 3?months and every month thereafter.

Results: Fifty out of 56 patients completed the 1-year study, which indicated that adjunctive topiramate was associated with a significant reduction of new manic and depressive episodes compared to the past 12?months. The most common adverse effects were reduced appetite, fatigue and somnolence.

Conclusions: This was an open-label, uncontrolled study involving retrospective evaluation of episodes prior to the initiation of treatment, and the use of more than one mood stabilizer in a few patients. However, these preliminary observations of adjunctive topiramate as a maintenance treatment encourage further investigations, especially with controlled trials, for its long-term effect.     

The effect of adjunctive mood stabilizers on antipsychotic utilization pattern and health resource utilization for Medicaid enrollees with schizophrenia

ABSTRACT

Background: Prescribing adjunctive mood stabilizers to manage schizophrenia is prevalent, despite the lack of substantial evidence to support the long-term use of this treatment regimen.

Objective: The objective of this study was to assess the impact of using adjunctive mood stabilizers on antipsychotic utilization, total health expenditures, inpatient hospital­izations, long-term care stays, and emergency room (ER) visits for patients with schizophrenia.

Methods: Georgia Medicaid claims from 1999 through 2001 were analyzed to identify recipients diagnosed with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD?9?CM]: 295.XX). The treatment groups consisted of subjects who received combination therapy of mood stabilizers and anti­psychotics (including both atypical and typical medica­tions), while the comparison group consisted of subjects who were on antipsychotic medications without exposure to the mood stabilizers under investigation. Four treatment groups (valproate, lithium, carbamazepine, and combina­tion mood stabilizer therapy) were formed based on the mood stabilizers patient received. Differences in annual health care use and expenditures were estimated between propensity score matched treatment and comparison groups controlling for comorbidity, prior utilization, demographic, and health provider specialty.

Results: During the 1?year observation period, subjects in treatment groups filled an average of 200-days supply of adjunctive mood stabilizers. These adjunctive mood stabilizer recipients had significantly longer antipsychotic treatment durations than the subjects who did not have exposure to mood stabilizers (valproate + antipsychotic vs. antipsychotic only, net difference: 56.47 days, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: 90.25 days, p < 0.0001; carbamazepine + antipsychotic vs. antipsychotic only, net difference: 41.27 days, p = 0.0439; multiple mood stabilizers + anti­psychotic vs. antipsychotic only, net difference: 83.14 days, p < 0.0001). The intensive pharmacotherapy associated with treatment groups resulted in $900–$1300 higher pharmacy costs than the comparison groups (valproate + antipsychotic vs. antipsychotic only, net difference: $1218.43, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: $985.79, p = 0.0015; carbamazepine + antipsychotic vs. anti­psychotic only, net difference: $911.63, p = 0.0497; multiple mood stabilizers + antipsychotic vs. antipsychotic only, net difference: $1281.91, p < 0.0047). However, there were no statistically significant differences for total health expenditures, hospitalizations, emergency room visits, and nursing home admissions between propensity-matched treatment and control groups.

Conclusions: There were no differences in health care costs or utilization of ER, long-term care, and inpatient services between schizophrenia patients who did and did not receive adjunctive mood stabilizer; however, longer anti­psychotic treatment durations were observed in patients receiving adjunctive mood stabilizers. Interpretation of these results is limited by the unknown selection bias between the treatment and the comparison groups and the relatively small number of patients in some treatment groups. The development of a better-controlled study to further evaluate this treatment regimen is warranted.     

Evaluation of the effects of propylisopropylacetic acid (PIA) on neuronal growth cone morphology

Propylisopropylacetic acid (PIA) is a constitutional isomer of valproic acid (VPA). It has previously been found to be a weak antiepileptic, but in common with mood stabilizers, causes inositol depletion and growth cone spreading, suggesting the basis of a new series of mood stabilizers. To assess this possibility, we have compared the effects of racemic (R,S)-PIA and its individual enantiomers to those of the mood stabilizers lithium (Li⁺), VPA and carbamazepine (CBZ). Unlike Li⁺ and VPA, but in common with CBZ and (R,S)-PIA, neither (R)-PIA nor (S)-PIA enantiomer induces T-cell factor (TCF)-mediated gene expression. However, as seen for other mood stabilizers, both enantiomers are potent inducers of growth cone spreading. To investigate the mechanism for these effects, we examined changes in the actin cytoskeleton following drug treatment with Li⁺, VPA, CBZ, (R,S)-PIA or its individual enantiomers. All exhibit a re-distribution of F-actin to the growth cone periphery, a feature of spread growth cones. (R,S)-PIA has the strongest effect as it also elevates F-actin polymerization at the cell periphery. This change in the actin cytoskeleton is associated with a substantial increase in F-actin-rich protrusions on the surface of the growth cone and in its close vicinity. These results demonstrate an effect of (R,S)-PIA on the neuronal actin cytoskeleton shared in common with other mood stabilizers, and suggest a potential to induce structural changes within the CNS.