拉莫三嗪治疗双相心境障碍对照研究

目的：探讨拉莫三嗪治疗双相情感障碍的疗效与安全性。方法：双相心境障碍患者135例，其中双相抑郁78例，躁狂57例。将患者随机分为3组，每组抑郁相26例，躁狂相19例。疗程32周。前8周为急性期治疗阶段，对照组抑郁相只服选择性5-羟色胺回收抑制剂（SSRI）类抗抑郁剂，躁狂相只服利培酮；拉莫三嗪组在对照组用药的基础上加服拉莫三嗪；碳酸锂组在对照组用药的基础上加服碳酸锂。后24周为巩固治疗阶段，所有患者随机分为两组，只服拉莫三嗪或碳酸锂。采用汉密尔顿抑郁量表（HAMD）、Young躁狂评定量表（YMRS）、治疗中出现的症状量表（TESS）评定疗效及安全性。结果：急性期治疗结束后，无论躁狂相还是抑郁相，拉莫三嗪组和碳酸锂组的临床疗效显著高于对照组（P〈0．01或〈0．05）。巩固治疗阶段两组相比，拉莫三嗪的抗抑郁作用较好，碳酸锂的抗躁狂作用较强。不良反应发生率，碳酸锂组40％，拉莫三嗪组22％。巩固治疗阶段病情复发率，拉莫三嗪组8％，碳酸锂组11％，两组差异无显著性（P〉0．05）。结论：拉莫三嗪作为心境稳定剂治疗双相情感障碍疗效可靠，不良反应小，与碳酸锂相比，抗抑郁作用更强。     

抗抑郁药物治疗抑郁发作3个月引发转躁的前瞻性观察

目的前瞻性探讨抗抑郁药物在治疗抑郁发作过程中出现转相的几率。方法对符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)和《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)中抑郁发作或双相抑郁诊断标准的190例接受抗抑郁药物治疗的抑郁发作患者,在医生针对性选择抗抑郁药物治疗情况下进行为期3个月的前瞻性观察,评价转相发生率。结果 1 3个月的治疗中,190例患者转相18例,转相率为9.47%。2男性患者转相率为6.56%,女性患者转相率为10.85%,差异无统计学意义(χ2=0.89,P0.05)。3单相抑郁与双相抑郁患者转相率分别为5.88%和40.00%,差异有统计学意义(χ2=24.29,P0.01)。4应用心境稳定剂与未使用心境稳定剂者转相率分别为13.8%和8.44%,差异无统计学意义(χ2=1.47,P0.05)。5服用2种或2种以上抗抑郁药物者与仅服用一种抗抑郁药物者转相率分别为12.96%和8.08%,差异无统计学意义(χ2=1.07,P0.05)。6有心境障碍家族史者与无心境障碍家族史者转相率分别为18.4%和7.23%,差异有统计学意义(χ2=4.43,P0.05)。7转相时间大约在用药后一个月左右。8各种抗抑郁药物转相几率差异不明显。结论抑郁发作患者在抗抑郁药物治疗下会出现一定比例的转相。     

脑源性神经营养因子血清浓度与双相障碍关系横断面研究

背景近年来发现,脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）的血清浓度与双相障碍症状关系的研究结果不一致。目的检验BDNF血清浓度与双相障碍的关系,并讨论双相障碍家族史在两者关系中的作用。方法检测了228例双相障碍患者和153名健康对照者的BDNF血清浓度,采用杨氏躁狂量表和汉密尔顿抑郁量表（17项）评估患者的躁狂或抑郁症状,将杨氏躁狂量表评分≥20分定义为躁狂发作,共计85例;将汉密尔顿抑郁量表评分≥17分定义为抑郁发作,共计14例;将杨氏躁狂量表评分〈20分并且汉密尔顿抑郁量表评分〈17分定义为缓解期,共计129例。结果患者组平均（标准差）BDNF血清浓度低于健康对照组[18．75（8．98）ng／d比23．72（5．60）．g／ml,t=6．09,P〈0．001】,且各个亚组（躁狂组、抑郁组和缓解期组）与健康对照组BDNF血清浓度的差异均有统计学意义。躁狂发作期与缓解期之间的BDNF血清浓度差异有统计学意义,其余各亚组间的差异无统计学意义。在多元线性回归模型中控制各个因素后,发现仅有杨氏躁狂量表评分与BDNF血清浓度呈正相关（标准回归系数=0．17,P=0．011）。结论双相障碍患者的BDNF血清浓度低于健康对照组,BDNF血清浓度与躁狂症状存在正相关,与是否存在家族史并不相关。     

双相情感障碍混合发作血清细胞因子水平研究

目的：比较双相情感障碍混合发作与躁狂发作及抑郁发作患者之间血清细胞因子的水平。方法：采用酶联免疫吸附法测定38例双相情感障碍混合发作患者（混合组）、54例躁狂发作患者（躁狂组）、47例抑郁发作患者（抑郁组）及38名正常人（对照组）血清白介素-1（IL-1β）、白介素-2（IL-2）及白介素-6（IL-6）的浓度;混合组患者于治疗前和治疗8周进行Hamilton抑郁量表（HAMD-24）和Young躁狂量表（YMRS）评定。结果：混合组IL-1β浓度显著高于躁狂组及抑郁组（P〈0.01）,但与对照组差异无统计学意义（P〉0.05）。混合组IL-2浓度与躁狂组、抑郁组及对照组之间差异均无统计学意义（P〉0.05）。混合组IL-6浓度显著高于躁狂组、抑郁组及对照组（P〈0.001）。混合组IL-6浓度治疗8周后较治疗前显著下降（t=3.372,P〈0.01）,与对照组比较差异无统计学意义（t=1.823,P〉0.05）。混合组治疗前后IL-6浓度差值与HAMD-24、YMRS减分率之间均无显著相关（r分别=-0.211、-0.100,P均〉0.05）。结论：双相情感障碍混合发作可能存在IL-6诱导的免疫功能异常,有不同于双相情感障碍躁狂发作及抑郁发作的生物学特征。     

抗抑郁剂联合心境稳定剂治疗双相障碍患者:1年随访

目的:观察抗抑郁剂联合心境稳定剂治疗双相障碍1年的结局,并评价不同疗效对双相抑郁结局的影响。方法:选择符合ICD-10双相障碍诊断标准患者,急性期进行8周抗抑郁剂和心境稳定剂联合治疗,痊愈和有效者进入1年维持治疗期。用24项汉密顿抑郁量表(HAMD)、Bech-Rafaelsen躁狂量表(BRMS)和临床疗效总评量表(CGI)评定疾病严重程度和疗效。结果:76例患者急性期治疗痊愈者53例,有效者23例。随访1年后,共43例(56.57%)维持痊愈,17例症状复发,总复发率22.36%。痊愈组36例(67.92%)仍保持痊愈,有效组7例(30.43%)达痊愈,两组差异有显著性(χ2=9.176,P=0.002)。痊愈组抑郁复发率低于有效组(3.77%vs.17.39%,χ2=4.091,P=0.045),两组转躁率差异无统计学意义(11.32%vs.21.74%;χ2=1.406,P=0.236)。生存分析显示痊愈组平均复发时间显著长于有效组[(10.06±2.14)个月vs.(9.00±3.67)个月;u=9.327,P=0.002]。结论:抗抑郁剂联合心境稳定剂治疗双相障碍抑郁发作患者1年后复发率低,急性期治疗痊愈者优于非痊愈者。     

重视从抑郁障碍中识别双相抑郁

明确区分单相抑郁(即反复发作抑郁症)和双相抑郁具有重要的实践意义。因为，二者的治疗不同。若诊断为单相抑郁，通常应予抗抑郁剂；但若为双相抑郁，标准治疗应是心境稳定剂，不恰当地使用抗抑郁剂容易导致由抑郁转为躁狂相(以下简称转相)而使病情恶化。在临床上，     

儿童和青少年躁狂的治疗

儿科双相障碍的临床样本率为6％，其发作可致严重残疾、共患物质滥用和学习成绩下降。1表现1．1混合性躁狂有两种定义。一种是躁狂与重性抑郁症有重叠时间；第二种是躁狂至少与其中一种抑郁障碍（包括重性抑郁症、轻性抑郁或心境恶劣）有重叠时间。在儿童和青少年早期双相Ⅰ型障碍组，伴重性抑郁症的混合性躁狂率为54．8％（1／2），伴重性抑郁症、轻性抑郁或心境恶劣的混合躁狂率为88．2％（9／10）。     

双相障碍治疗前后催乳素、雌二醇水平的改变 及其与临床疗效的关系

目的 探讨双相障碍治疗前后催乳素（PRL）、雌二醇（E2）水平变化及其与临床疗效的关 联。方法 选取2014年1月—2015年5月收住北京回龙观医院的符合ICD-10标准的双相障碍患者57例（男 36 例,女21 例）,其中双相躁狂39 例,双相抑郁18 例。入组后患者接受药物治疗,治疗时间为6 周,采用 汉密尔顿抑郁量表24项版（HAMD-24）评估抑郁症状,采用贝克-拉范森躁狂量表（BRMS）评估躁狂症状。 使用化学发光免疫分析法检测研究对象周围血中E2、PRL水平。结果 与基线相比,治疗后双相障碍患 者PRL浓度降低,差异有统计学意义（P=0.01）,E2浓度未见明显升高（P＞0.05）。双相躁狂组PRL水平降 低,差异有统计学意义（P=0.01）。双相抑郁组PRL、E2浓度变化均不明显（P＞0.05）。双相躁狂组治疗前 BRMS评分及双相抑郁组治疗后HAMD-24评分均下降,差异有统计学意义（均P＜0.01）。躁狂组治疗前 PRL水平与BRMS评分呈正相关（r=0.41,P＜0.01）,躁狂组治疗前后PRL变化值及E2变化值与BRMS减分 值呈正相关（r=0.39,P＜0.01;r=0.33, P=0.03）。结论 双相障碍、躁狂发作患者治疗后PRL均下降,躁狂 发作患者的症状、疗效与PRL水平的变化可能存在一定相关性。     

10省市双相情感障碍患者药物治疗的现况调查

目的了解国内双相情感障碍患者精神药物的治疗现状。方法按一定的抽样比例，选择10个省市46家专科医院或综合医院精神科同时进行药物处方方式的调查。结果（1）在558例双相情感障碍患者中，躁狂相472例（84．6％），抑郁相86例（15．4％）；555（99．5％）例患者接受精神药物治疗。（2）主要治疗药物为心境稳定剂（80．7％），404例（72．8％）患者使用了抗精神病药。（3）躁狂相患者以心境稳定剂（84．7％）和抗精神病药（81．4％）单一或联合治疗为主，抑郁相患者单一或联合使用抗抑郁药的频率较高（80．2％）。（4）联合两种及其以上药物治疗者占80．2％。（5）145例（26．1％）患者合并使用了苯二氮Zhuo类药。结论国内双相情感障碍药物处方方式与国内外的指南推荐方案基本相符；双相障碍抑郁相抗抑郁药使用频率较高，有待于将来的临床实践论证。     

喹硫平治疗心境障碍的作用机制

双相情感障碍，简称双相障碍（BPD），是针对单相情感障碍（重性抑郁）而言。DSM—Ⅳ和ICD-10将二者并列为两种主要心境障碍。顾名思义，双相兼有心境变高和变低两极性特点，是心境在正常，高涨（躁狂），低落（抑郁）之间往返摆动。DSM—Ⅳ将双相障碍又分为若干个亚型，这在诊断上是一个重要变更，突出表现在分出了双相Ⅰ型和双相Ⅱ型，基本区别是前者一般以躁狂发作严重；后者以抑郁发作严重，躁狂发作较轻，且家族史中阳性率高，发作次数多，对治疗反应差。流行病学资料显示，双相Ⅰ型发病率为0．5％～2．4％，双相Ⅱ型发病率为0．2％-5．0％。双相障碍是精神科常见病，多发病，具有较高同病率（焦虑障碍，酒依赖，药物依赖）与较高死亡率（特别是在抑郁相或者混合状态）特点。目前有关躁狂症状的治疗已有很大进展；而抑郁症状则被认为治疗困难，传统抗抑郁药物或心境稳定剂疗效均不佳。美国最近一项研究发现，喹硫平除对躁狂症状（单药或喹硫平＋锂盐／双丙戊酸钠）或精神分裂症疗效明确外，还能控制抑郁症状，从而提高患者生活质量。因此，喹硫平是目前唯一被FDA批准单药既可用于治疗双相躁狂急性发作，     

Antidepressants for bipolar depression: a systematic review of randomized, controlled trials

OBJECTIVE: This study reviewed the evidence from randomized, controlled trials on the efficacy and safety of antidepressants in the short-term treatment of bipolar depression. METHOD: The authors performed a systematic review and meta-analysis of randomized, controlled trials. They searched the Cochrane Collaboration Depression, Anxiety, and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE, EMBASE, CINAHL, PsycLIT, PSYNDEX, and LILACS. The main outcome measures were the proportion of patients who clinically responded to treatment and the rate of switching to mania. RESULTS: Twelve randomized trials were included, with a total of 1,088 randomly assigned patients. Five trials compared one or more antidepressants with placebo: 75% of these patients were receiving a concurrent mood stabilizer or an atypical antipsychotic. Antidepressants were more effective than placebo. Antidepressants did not induce more switching to mania (the event rate for antidepressants was 3.8% and for placebo, it was 4.7%). Six trials allowed comparison between two antidepressants. The rate of switching for tricyclic antidepressants was 10%, and for all other antidepressants combined, it was 3.2%. CONCLUSIONS: Antidepressants are effective in the short-term treatment of bipolar depression. The trial data do not suggest that switching is a common early complication of treatment with antidepressants. It may be prudent to use a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor rather than a tricyclic antidepressant as first-line treatment. Given the limited evidence, there is a compelling need for further studies with longer follow-up periods and careful definition and follow-up of emerging mania and partial remission.     

Do antidepressants influence mood patterns? A naturalistic study in bipolar disorder

This prospective, longitudinal study compared the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. One hundred and eighty-two patients with bipolar disorder self-reported mood and psychiatric medications for 4 months using a computerized system (ChronoRecord) and returned 22,626 days of data. One hundred and four patients took antidepressants, 78 did not. Of the antidepressants taken, 95% were selective serotonin or norepinephrine reuptake inhibitors, or second-generation antidepressants. Of the patients taking an antidepressant, 91.3% were concurrently taking a mood stabilizer. The use of antidepressants did not influence the daily rate of switching from depression to mania or the rate of rapid cycling, independent of diagnosis of bipolar I or II. The primary difference in mood pattern was the time spent normal or depressed. Patients taking antidepressants frequently remained in a subsyndromal depression. In this naturalistic study using self-reported data, patients with bipolar disorder who were taking antidepressants--overwhelmingly not tricyclics and with a concurrent mood stabilizer--did not experience an increase in the rate of switches to mania or rapid cycling compared to those not taking antidepressants. Antidepressants had little impact on the mood patterns of bipolar patients taking mood stabilizers.     

我国部分精神科医生关于抗抑郁治疗与转躁认识的初步调查

目的：了解我国精神科高级职称医生对双相抑郁治疗过程中抗抑郁药物与躁狂转化的认识。方法：自编与双相抑郁治疗有关的因素评价表让全国各地的专科医生根据自己的经验进行选择。结果：调查信回收率70％，有56位医生回答了全部问题。医生认为，使用抗抑郁药物(94．6％)、联合多种抗抑郁药物(64．2％)、不同时应用心境稳定剂(50．9％)与双相抑郁治疗过程中引发躁狂有关。结论：我国精神科高级职称医生对双相抑郁治疗过程中药物引起躁狂发作的认识比较全面。     

Advances in the pharmacologic treatment of bipolar depression.

The pharmacologic treatment of bipolar depression has not been well studied in randomized, controlled trials. Thus important clinical questions regarding the efficacy in bipolar depression of mood stabilizers, antidepressants, and new antiepileptic and atypical antipsychotic agents have been relatively unaddressed. Until recently there were few data regarding the degree to which mood stabilizers reduce the risk of switching associated with antidepressant treatment. Likewise, although treatment guidelines have often recommended limiting antidepressant exposure in the maintenance treatment of bipolar depression, the potential risks of depressive relapse after antidepressant discontinuation were largely unknown. We review here data from new randomized, controlled trials published or presented during the past 5 years regarding the efficacy of antidepressants, mood stabilizers, lamotrigine, and olanzapine in the acute and maintenance treatment of bipolar depression. We also review new studies clarifying the protective effect of coadministration of mood stabilizers from antidepressant-associated switching and the risk of depressive relapse when antidepressants are discontinued during maintenance treatment.     

Mood changes related to antidepressants: a longitudinal study of patients with bipolar disorder in a naturalistic setting

This prospective, longitudinal study investigated the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. Eighty patients with bipolar disorder self-reported mood and psychiatric medications daily for 3 months using a computerized system (ChronoRecord) and returned 8662 days of data. Of the total group of 80 patients, 47 took antidepressants; 33 did not. Patients taking antidepressants reported depression twice as frequently (29% of days vs. 13.8% of days). In both groups, two-thirds of all mood changes over a 1-, 2- and 3-day period were small, between -5 and 5 on a 100-point scale. No statistically significant difference was found in the frequency of large mood changes (>10 on a 100-point scale) or in switches between depression and mania (0.7% if not taking antidepressants vs. 0.9% if taking), independent of diagnosis of bipolar I or II. Eighty-nine percent of patients taking antidepressants were also taking mood stabilizers. In this naturalistic setting, no significant difference between the rate of switches to mania or rapid cycling was found between those taking and not taking antidepressants, regardless of diagnosis. The primary difference in pattern between the groups was the time spent in depressed or normal mood, with minor daily mood variations.     

Risperidone and paroxetine given singly and in combination for bipolar depression

BACKGROUND: Bipolar depression is a major clinical problem that remains under-researched. The current study was intended to evaluate the effects of the novel antipsychotic risperidone, the selective serotonin reup-take inhibitor (SSRI) paroxetine, and the combination in patients with bipolar disorder. METHOD: Thirty patients with DSM-IV bipolar (I or II) disorder, depressed phase, who were receiving a stable dose of a mood stabilizer were randomly assigned to 12 weeks of double-blind treatment with risperidone (plus placebo), paroxetine (plus placebo), or the combination of risperidone and paroxetine. Data were gathered from August 1999 to September 2001. RESULTS: All 3 groups experienced significant reductions in depression ratings from baseline to endpoint; there were no significant differences in outcome between groups. There were statistically significant differences in paroxetine dose contrasting paroxetine plus placebo against the combined condition. The switch rate into mania or hypomania was very low, with only 1 patient in the paroxetine plus placebo condition experiencing mild hypomania. CONCLUSION: These results suggest that risperidone, paroxetine, and the combination of risperidone and paroxetine are equally but modestly effective when added to a mood stabilizer in bipolar depression. The paroxetine dose differed between groups, possibly because of drug-drug interactions. Using another SSRI in the combined condition could have produced a more robust effect and should be tested.     

New approaches in managing bipolar depression

Historically, the pharmacologic treatment of bipolar depression has not been well studied. New data are beginning to emerge regarding the efficacy of new medications and the use of combinations of mood stabilizers and antidepressants in acute and long-term treatment of bipolar depression. We reviewed data from recent randomized, controlled trials of mood stabilizers and antidepressants in the treatment of bipolar depression and naturalistic studies examining the risk of switching and depressive relapse with ongoing antidepressant treatment.     

Antidepressant treatment in bipolar versus unipolar depression

OBJECTIVE: Antidepressant responses were compared in DSM-IV bipolar and unipolar depression. METHOD: The authors analyzed clinical records for outcomes of antidepressant trials for 41 patients with bipolar depression and 37 with unipolar depression, similar in age and sex distribution. RESULTS: Short-term nonresponse was more frequent in bipolar (51.3%) than unipolar (31.6%) depression. Manic switching occurred only in bipolar depression but happened less in patients taking mood stabilizers (31.6% versus 84.2%). Cycle acceleration occurred only in bipolar depression (25.6%), with new rapid cycling in 32.1%. Late response loss (tolerance) was 3.4 times as frequent, and withdrawal relapse into depression was 4.7 times less frequent, in bipolar as in unipolar depression. Mood stabilizers did not prevent cycle acceleration, rapid cycling, or response loss. Modern antidepressants, in general, did not have lower rates of negative outcomes than tricyclic antidepressants. CONCLUSIONS: The findings suggest an unfavorable cost/benefit ratio for antidepressant treatment of bipolar depression.     

Treatment of bipolar depression, a review of the literature and a suggestion for an algorithm

A review of the methodology and results of 9 controlled studies on the acute treatment of bipolar depression and the risk of switches into (hypo)mania is presented. There are indications but no proof for efficacy of mood stabilizers such as lithium, carbamazepine and valproate. Only lamotrigine has been shown to be effective, with a relative low risk of switching. Several antidepressants appear effective as well, but again there is no (placebo-controlled) proof of their efficacy. The only exception is tranylcypromine which has been found to be more effective than imipramine. The switch ratio into (hypo)mania by tricyclic antidepressants seems to be higher than by several other antidepressants, especially the selective serotonin reuptake inhibitors. In the acute treatment of bipolar depression, it is recommended to start with a mood stabilizer, and to add an antidepressant after 4-6 weeks in case of nonresponse. In severer cases, one might consider to start earlier with the combination of a mood stabilizer and an antidepressant, and in refractory patients, there is a place for tranylcypromine. In the maintenance treatment, there are indications that the combined treatment of a mood stabilizer (mostly lithium) and an antidepressant (TCA) is associated with an increased risk of switches into (hypo)mania, when compared to a mood stabilizer alone. Therefore, it is recommended to try whether a monotherapy with a mood stabilizer is effective, before combining it with an antidepressant.