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，     

拉莫三嗪对双相抑郁的治疗与预防

目前,双相障碍抑郁相(简称双相抑郁)的治疗已引起广泛关注,因为它的治疗与单相抑郁的治疗有所不同。如果将这些双相抑郁按单相抑郁治疗,就可能会引起躁狂发作或者引发快速循环。因此各国都制定了双相抑郁的治疗指南,其中心思想表明,双相抑郁的治疗在应用抗抑郁药物的同时应该联合心境稳定剂。这样,不仅使抑郁得到治疗,又最大限度地减少了抗抑郁药物引起的躁狂发作。同时也尽可能避     

我国精神科医生关于双相抑郁认识的调查

目的了解我国精神科医生对双相障碍的认识水平。方法自编与双相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,双相家族史、素质特点、某些症状以及症状特点、发病年龄早、女性等与双相障碍关系密切。结论我国精神科高级职称医生对双相障碍的认识全面。     

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。     

拉莫三嗪治疗双相Ⅰ型抑郁

现有的心境稳定药(包括锂)常只对躁狂效果较好,而对双相障碍时的抑郁疗效较差,加用抗抑郁药又有转发躁狂的可能。拉莫三嗪(lamotrigine)是80年代推出的抗癫痫新药,使用过程中发现它能改善心境与活力。已有一些有关此药治疗双相型与型情感障碍有效的非盲性临床报道。本文是有关此药治疗双相型抑郁的第一篇双盲安慰剂对照研究。方法:入组病例的条件如下:符合DSM-IV中双相型障碍的诊断标准,过去10年间至少有过2次情感障碍发作,其中至少一次为躁狂型或混合型,诊断经DSM-IV定式临床检查(SCID)所证实,当前为抑郁发作,当前发作的病期等于或长…     

几种治疗双相抑郁药物的疗效

尽管目前的统计数据表明双相躁狂与双相抑郁的患者数量相当，但大量的研究仍集中在双相躁狂的药物治疗上。例如，锂盐、卡马西平、丙戊酸盐都已经被证实对于治疗急性躁狂是有效的／[1-2／]。然而缺乏这些药物在治疗急性双相抑郁方面与安慰剂的对照研究。锂盐、抗癫痫药、抗抑郁药、非典型的抗精神病药物是临床常用的几种治疗双相抑郁药物，所以有必要将这几种药物在控制急性双相抑郁方面的疗效进行一下比较。     

抗抑郁药物与双相抑郁

双相抑郁,无论是双相Ⅰ型还是双相Ⅱ型抑郁,都需要解决抑郁症状,有时一定程度上还需要抗抑郁治疗.但是,双相抑郁的治疗必须建立在最基本的原则之上,这就是在抗抑郁的同时不能导致转向躁狂发作[1].然而在临床实践过程中,这种现象却无法避免.因此,近来的一个讨论主题是,双相抑郁的抗抑郁药物用还是不用,亦或如何使用?     

双相障碍的早期识别

双相障碍是一种高复发率(＞90％的患者反复发作)、高自杀率(25％～50％的患者自杀未遂,11％～19％的患者自杀死亡)、高共病率(46％的患者伴酒依赖,60％的患者伴药物依赖)的临床常见病[1].双相障碍的自然病程中,始终仅有躁狂或轻躁狂发作者很少(单纯躁狂约占双相障碍的1％),这些患者的家族史、病前人格、生物学特征、治疗原则及预后等与兼有抑郁发作的双相障碍相似[2].Akiskal[3]疾呼:双相障碍,尤其是双相抑郁大多被临床医生所忽略.     

使用抗抑郁药治疗双相抑郁——“食之无味，弃之可惜”？

双相抑郁是一个复杂的精神科临床问题,其诊断与治疗对治疗医生而言都具有挑战性。通常双相障碍整个病程中抑郁症状发生较多,因而双相障碍长期治疗的一个重要方面就是双相抑郁的药物治疗。双相障碍中,被批准用于躁狂相的治疗方法不少,但是双相抑郁急性期治疗的药物只有2种,一种是喹硫平,另一种是奥氮平和氟西汀的复合制剂。然而,大多数医生在临床实践中都使用抗抑郁药物控制双相抑郁,尤其是当患者要求用这类药物来减轻他们的“抑郁症”。     

对情感性精神障碍治疗的调查分析

目的：了解精神科医生对情感性精神障碍的治疗现状及疗效不佳时的处理。方法：采用医生自填问卷的方法，对140名精神科医生进行调查，内容为针对7例情感性精神障碍的问答题。结果：在抑郁发作中选用最多的药物为5－羟色胺再摄取抑制剂（SSRIs），尤为氟西汀，在重度抑郁及伴有精神病性症状时，首选电休克治疗（ECT），以无抽搐ECT为多，并以市级医院应用显著较多。在躁狂发作中选用最多的药物为碳酸锂，轻中度抑郁不理想时多改用另一种抗抑郁药。重度抑郁多选用ECT治疗。结论：抑郁发作的首选治疗由三环抗抑郁剂转向SSRIs。疗效不佳时治疗选择各不相同。     

Antidepressant-associated switches from depression to mania in severe bipolar disorder

OBJECTIVES: To determine whether switching from depression to mania is part of the natural history of bipolar illness or results from antidepressant (AD) treatment by examining bipolar patients with psychosis early in their illness course. METHODS: A multi-facility cohort of 123 first-admission inpatients, aged 15-60 years, with DSM-IV bipolar disorder (BD) with psychotic features, was followed for four years, and 76 individuals experienced at least one episode of depression. Frequency of and risk factors for switches from depression to mania, time to switch, and duration of the subsequent manic episode were examined in relation to AD use (with anti-manic and/or antipsychotic medications). RESULTS: The 76 respondents experienced 113 depressive episodes. Those prescribed ADs had more depressive episodes and spent more time depressed than non-users. A total of 23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode (20%). The time to switch and duration of the subsequent manic episode were not significantly different for the seven respondents and nine episodes involving AD treatment versus the 10 respondents and 14 episodes without ADs. None of the risk factors (age of onset 相似文献   

Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD

OBJECTIVE: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. METHOD: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by > or = 2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. RESULTS: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. CONCLUSIONS: In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy.     

Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder]

Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to the prevention of suicidal behavior and the careful use of antidepressants for bipolar (spectrum) disorder, but we must be prudent when applying this concept, since it has not yet been established.     

Carbamazepine in bipolar-depressed disorder complicated by tricyclic antidepressant switching: case report

The use of carbamazepine in a depressed bipolar patient with a history of manic switching with tricyclic antidepressants is described. Carbamazepine effectively treated the depression and mania was avoided.     

Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up

OBJECTIVE: While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode. METHOD: Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group"). RESULTS: A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse. CONCLUSIONS: The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.     

Disease mongering and bipolar disorder in Japan

Frequently used in a pejorative sense, "disease mongering" connotes a widening of the diagnostic boundaries of illness. Pharmaceutical companies conduct disease awareness campaigns on the pretext of educating the public about the prevention of illness or the promotion of health. Encouraged by disease awareness advertisements, people gradually become filled with concern that they are ill and need medical treatment. As a result, pharmacotherapy is increasingly being applied to ever-milder conditions, leading to potentially unnecessary medication, wasted resources, and even adverse side effects. Among all fields of clinical medicine, psychiatry is undoubtedly the most vulnerable to the danger of disease mongering. In Japan, depression provides the most drastic example of the impact of disease awareness campaigns on the number of patients seeking treatment. Until the late 1990s, Japanese psychiatrists focused almost exclusively on psychosis and endogenous depression, the latter being severe enough to require conventional forms of antidepressants, known as tricyclic antidepressants, and even hospitalization. At this time, people's attitude toward depression was generally unfavorable. Indeed, the Japanese word for clinical depression, utubyo, has a negative connotation, implying severe mental illness. This situation, however, changed immediately after fluvoxiamine (Luvox-Fujisawa, Depromel-Meiji Seika), the first selective serotonin re-uptake inhibitor (SSRI) to receive approval in Japan, was introduced in 1999. In order to aid the drug's acceptance by the Japanese public, pharmaceutical companies began using the catchphrase kokoro no kaze, which literally means "a cold of the soul". Thus armed with this phrase, the pharmaceutical industry embarked on a campaign to lessen the stigma surrounding depression. According to national data from the Ministry of Health and Welfare, the number of patients with a diagnosis of mood disorder increased from 327,000 in 1999 to 591,600 in 2003. At the same time, antidepressant sales have sextupled, from\14.5 billion in 1998 to\87 billion in 2006, according to statistics from GlaxoSmithKline. Recently, the pharmaceutical industry has shifted its focus from depression to bipolar disorder. Historically, Japanese psychiatrists have been familiar with Emil Kraepelin's "manic depressive insanity" (1899), whose definition was much narrower than that of its contemporary counterpart, bipolar disorder. Thus far, perhaps due partly to the reference in Kraepelin's definition of "manic depressive" disorder, Japanese psychiatrists have rather conservatively prescribed mood stabilizers for persons with frequent mood swings. Japanese psychiatrists can learn a great deal from their experience with the aggressive marketing of antidepressants. In the case of depression, over-medication arguably did more harm than good. The same risk exists with bipolar disorder. Disease mongering may occur whenever the interests of a pharmaceutical company exceed the expected benefits from the proposed pharmacotherapy on those affected by the putative bipolar disorder. In cases that are not severe enough for aggressive medication, psychiatrists should propose natural alternatives, such as an alteration of lifestyle and psychotherapy.     

单相抑郁与双相障碍住院患者地塞米松抑制试验的对照研究

目的 通过地塞米松抑制试验(DST)了解单相抑郁和双相障碍患者在不同情绪状态下的下丘脑-垂体-肾上腺轴功能改变情况. 方法对38例单相抑郁住院患者和63例双相障碍住院患者(双相障碍Ⅰ型19例,双相障碍Ⅱ型44例;双相障碍抑郁发作者33例,双相障碍躁狂发作者18例,双相障碍混合发作者12例)进行DST,其中17例单相抑郁、35例双相障碍患者在治疗4周后再次行DST,比较各组DST脱抑制率差异.结果 治疗前,单相抑郁的DST脱抑制率(36.8%)与双相障碍(14.3%)、双相障碍Ⅰ型(10.5%)、双相障碍Ⅱ型(15.9%)以及双相障碍抑郁发作(15.2%)之间比较差异有统计学意义(P<0.05);双相障碍Ⅰ型(10.5%)与双相障碍Ⅱ型(15.9%)之间,双相障碍抑郁发作(15.2%)、双相障碍混合发作(16.7%)和双相障碍躁狂发作(11.1%)两两比较差异均无统计学意义(P>0.05).治疗后,DST脱抑制率在上述各组间差异无统计学意义(P>0.05).治疗后单相抑郁的DST脱抑制率随着病情改善而降低,但较治疗前差异无统计学意义(P>0.05),双相障碍的DST脱抑制率在治疗前后比较差异无统计学意义(P>0.05).结论在疾病期,单相抑郁的DST脱抑制率高于双相障碍;双相障碍的DST脱抑制率与临床分型、发作类型、病情无关.     

A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network

Objectives: The risk‐to‐benefit ratio of the use of unimodal antidepressants (ADs) as adjuncts to mood stabilizers continues to be an area of controversy and disagreement among experts in the field. This paper reviews new data on: (1) depression in bipolar illness, (2) switch rates on ADs and (3) risks of AD discontinuation that are pertinent to the ongoing discussion and recommendations. Methods: In the first study reviewed, 258 outpatients with bipolar illness were assessed prospectively on a daily basis using the National Institute of Mental Health‐Life Chart Method^TM (NIMH‐LCM) for 1 year. In the second study, 127 bipolar depressed patients were randomized to 10 weeks of sertraline, bupropion, or venlafaxine, as adjuncts to mood stabilizers; non‐responders were re‐randomized and responders were offered a year of continuation treatment. In the final study, Altshuler et al. retrospectively and prospectively assessed the risk of depressive relapses in patients who remained on ADs after 2 months of euthymia compared with those who discontinued ADs. Results: Despite intensive naturalistic treatment, the 258 outpatients with bipolar illness followed prospectively for 1 year showed three times as many days depressed as days manic, re‐emphasizing the considerable depressive morbidity that remains in bipolar disorder despite the number of treatment options available. In the study of bipolar depressed patients randomized to one of three ADs, a range of severities and durations of hypomanic to manic switches were discerned following 175 trials of AD augmentation of treatment with a mood stabilizer. Of the acute 10‐week trials, 9.1% were associated with switches into hypomania or mania and another 9.1% with a week or more of hypomania alone (with no to minimal dysfunction). In 73 continuation phase AD trials, 16.4 and 19.2% were similarly associated with hypomanic to manic and hypomanic switches, respectively. In the Altshuler et al. studies, those who remained well on any AD for more than 2 months (only 15–20% of those initially treated) and who continued on ADs showed a lesser rate of relapse into depression over 1 year (35 and 36% in the first and second study, respectively) compared with those who discontinued their ADs (68 and 70% relapsing into depression). Surprisingly, this continuation of ADs was associated with no increase in the rate of switching into mania compared with those stopping ADs. Conclusions: These data reveal that depression and depressive cycling remain a substantial problem in some two‐thirds of intensively treated bipolar outpatients. Acute AD augmentation was associated with a modest response rate and 18.2% switched into a hypomanic to manic episode, and 35.6% of the continuation trials showed these two types of switches. Two separate studies suggest that in the very small subgroup who remain well on ADs for at least 2 months, one should consider continuation of this AD augmentation treatment, because AD discontinuation appears associated with a substantially increased risk of depression relapse over the subsequent year with no reduced risk of switching into mania.     

重性抑郁障碍或双相障碍患者抑郁发作伴随躁狂症状的临床特征

目的:了解重性抑郁障碍(MDD)或双相障碍抑郁发作患者出现躁狂症状的频率和程度。方法:对52例经简明国际神经精神访谈(MINI)、符合《美国精神障碍诊断与统计手册》第4版(DSMIV)重性抑郁障碍或双相障碍抑郁发作的患者,采用情感障碍评估量表(ADE)评估患者本次抑郁发作中出现的躁狂症状。结果:52例患者中有36例重性抑郁障碍,16例为双相障碍抑郁发作。至少有1条躁狂症状的患者达86.5%(n=45),至少有3条躁狂症状的患者占32.7%(n=17),而没有任何躁狂症状的患者仅占13.5%(n=7)。结论:抑郁发作患者大多存在不同程度的躁狂症状,及时识别这些症状,对诊断与治疗有指导意义。情感障碍评估量表是一个值得应用的评估情感发作的工具。     

Antidepressant-induced mania in bipolar patients: identification of risk factors

BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.