Akiskal Hagop S, Benazzi Franco, Perugi Giulio, Rihmer Zoltán
Department of Psychiatry and International Mood Center, University of California, La Jolla, CA, USA.
J Affect Disord. 2005 Apr;85(3):245-58. doi: 10.1016/j.jad.2004.12.004.
The nosologic status of agitated depression is unresolved. Are they unipolar (UP) or bipolar (BP)? Are they mixed states? Even more controversial is the notion that antidepressants might play some role in the suicidality of such patients (Akiskal and Mallya, 1987) [Akiskal, H.S., Mallya, G., 1987. Criteria for the "soft" bipolar spectrum: treatment implications. Psychopharmacol Bull. 23, 68-73].
After excluding all patients with history of hypomanic episodes occurring outside the frame of a major depressive episode (MDE), even those with a shorter duration of hypomanic symptoms than stipulated in DSM-IV, the remaining consecutive 254 unipolar major depressive disorder (MDD) private adult (> 21 years old) outpatients were interviewed (off psychoactive drugs for 2 weeks) with the Structured Clinical Interview for DSM-IV (SCID-CV), the Hypomania Interview Guide (HIGH-C), and the Family History Screen. Intra-MDE hypomanic symptoms were systematically assessed, with > or = 3 such symptoms required for a diagnosis of depressive mixed state (DMX). Agitated depression was defined as an MDE with HIGH-C psychomotor agitation score > or = 2. Logistic regression was used to study associations and control for confounding variables.
In this strictly defined unipolar sample, agitated depression was present in 19.7%. Compared with its non-agitated counterpart, it had significantly fewer recurrences, less chronicity, higher rate of family history for bipolar disorder, and DMX; and, among the intra-depressive non-euphoric hypomanic symptoms (in decreasing order of frequency), distractibility, racing/crowded thoughts, irritable mood, talkativeness, and risky behavior. The most striking finding was the robust association between agitated depression and DMX (OR = 36.9). Furthermore, patients with psychomotor agitation had significantly higher rate of weight loss and suicidal ideation. Of DMX symptoms, we found an association between suicidal ideation, psychomotor activation, and racing thoughts. Agitated depression was tested by forward stepwise logistic regression versus all variables significantly different in the pairwise comparisons, yielding DMX, talkativeness, and suicidal ideation as the independent significant positive predictors.
No suicidal ideation scale was used.
Agitated depression emerges as a distinct affective syndrome with weight loss, pressure of speech, racing thoughts and suicidal ideation. Psychomotor activation and racing thoughts during MDD independently predicted suicidal ideation. In this "unipolar" MDD sample, agitated depression had a strong clustering of intra-episode non-euphoric hypomanic symptoms (i.e. DMX) which, coupled with its association with bipolar family history, support its link with the bipolar spectrum. Agitated depression is therefore best regarded as "pseudo-unipolar." These findings overall accord with classical German concepts of agitated depression as a mixed state. Given that these patients are typically activated along the lines of risk-taking behavior, Kraepelin's rubric of "excited (mixed) depression" appears to us the preferred terminology over "agitated depression".
The data reported herein, placed in the setting of the literature reviewed in the discussion suggest that the reports of increased risk of suicidal ideation and/or behavior in some depressed patients treated by antidepressant monotherapy or combinations thereof might be attributed to baseline psychomotor activation/agitation as part of an unrecognized bipolar mixed state. Whether antidepressants induce de novo suicidality in MDD cannot be answered without adequately powered prospective double-blind studies, unlikely to be conducted because of ethical constraints. Nonetheless, we submit that agitated, activated, or otherwise excited depressions (which we consider as depressive mixed states) overlap considerably with the so-called antidepressant "activation syndrome." Furthermore, the rare occurrence of suicidality on antidepressants should not obscure the fact that the advent of the new antidepressants is associated with worldwide decline in suicide rates. We finally wish to point out that our formal nosology (i.e. DSM-IV and ICD-10), in its failure to recognize the bipolar nature of depressive mixed states, thereby fails to shield pseudo-unipolar patients from antidepressant monotherapy, which is inappropriate for such patients.
激越性抑郁的疾病分类状况尚无定论。它们是单相（UP）还是双相（BP）？它们是混合状态吗？更具争议的是，抗抑郁药可能在这类患者的自杀行为中起某种作用这一观点（阿基斯卡尔和马利亚，1987年）[阿基斯卡尔，H.S.，马利亚，G.，1987年。“软”双相谱系的标准：治疗意义。《精神药理学通报》。23，68 - 73]。
排除所有在重度抑郁发作（MDE）框架之外有轻躁狂发作史的患者，即使那些轻躁狂症状持续时间短于《精神疾病诊断与统计手册》第四版（DSM - IV）规定的患者后，对其余连续的254例单相重度抑郁症（MDD）成年（>21岁）门诊患者（停用精神活性药物2周）进行访谈，采用DSM - IV结构化临床访谈（SCID - CV）、轻躁狂访谈指南（HIGH - C）和家族史筛查。系统评估MDE期间的轻躁狂症状，诊断抑郁混合状态（DMX）需要≥3种此类症状。激越性抑郁定义为HIGH - C精神运动性激越评分≥2的MDE。采用逻辑回归研究关联并控制混杂变量。
在这个严格定义的单相样本中，激越性抑郁的发生率为19.7%。与非激越性抑郁相比，其复发次数显著减少，慢性化程度较低，双相情感障碍家族史发生率较高，且DMX发生率较高；在抑郁期非欣快性轻躁狂症状中（按频率递减顺序），有注意力分散、思维奔逸/杂乱、易激惹情绪、健谈和危险行为。最显著的发现是激越性抑郁与DMX之间有很强的关联（比值比 = 36.9）。此外，精神运动性激越的患者体重减轻和自杀观念的发生率显著更高。在DMX症状中，我们发现自杀观念、精神运动性激活和思维奔逸之间存在关联。通过向前逐步逻辑回归对激越性抑郁与两两比较中所有显著不同的变量进行检验，得出DMX、健谈和自杀观念是独立的显著正向预测因子。
未使用自杀观念量表。
激越性抑郁表现为一种独特的情感综合征，伴有体重减轻、言语紧迫感、思维奔逸和自杀观念。MDD期间的精神运动性激活和思维奔逸独立预测自杀观念。在这个“单相”MDD样本中，激越性抑郁有强烈的发作期非欣快性轻躁狂症状（即DMX）聚集，再加上其与双相情感障碍家族史的关联，支持了其与双相谱系的联系。因此，激越性抑郁最好被视为“假性单相”。这些发现总体上与德国关于激越性抑郁为混合状态的经典概念一致。鉴于这些患者通常表现出冒险行为倾向，我们认为克雷佩林的“激越性（混合性）抑郁”这一类别比“激越性抑郁”更适合作为首选术语。
本文报道的数据，结合讨论中回顾的文献背景表明，一些接受抗抑郁药单药治疗或联合治疗的抑郁症患者自杀观念和/或行为风险增加的报告，可能归因于作为未被识别的双相混合状态一部分的基线精神运动性激活/激越。由于伦理限制，不太可能进行有足够效力的前瞻性双盲研究，因此无法回答抗抑郁药是否会在MDD中诱发新发自杀行为。尽管如此，我们认为激越性、激活性或以其他方式表现为兴奋的抑郁症（我们认为是抑郁混合状态）与所谓的抗抑郁药“激活综合征”有很大重叠。此外，抗抑郁药导致自杀行为罕见这一事实不应掩盖新抗抑郁药的出现与全球自杀率下降相关这一事实。我们最后想指出，我们现行的疾病分类学（即DSM - IV和ICD - 10）未能认识到抑郁混合状态的双相性质，从而未能使假性单相患者避免接受不适合此类患者的抗抑郁药单药治疗。
