Koukopoulos A, Sani G, Koukopoulos A E, Minnai G P, Girardi P, Pani L, Albert M J, Reginaldi D
Centro Lucio Bini-Roma, Via Crescenzio 42, Rome 00193, Italy.
J Affect Disord. 2003 Jan;73(1-2):75-85. doi: 10.1016/s0165-0327(02)00321-x.
Recognition by the DSM-IV of rapid cyclicity as a course specifier has raised the question of the stability and long-term outcome of rapid-cycling (RC) patients. Data on this topic is sparse and often inconsistent. To our knowledge, these are the first personally followed patients over the long term, dealing directly with the issue of the duration of the RC course.
We examined the evolution of the course of 109 RC patients (68 women and 41 men) followed for a minimum of 2 years and up to 36 years, beginning with the index episode when the RC course was diagnosed by the authors (A.K., G.P.M., P.G., L.P., D.R.). Patients were included in the study if they met criteria for RC as defined by>or=4 affective episodes per year (Dunner and Fieve, 1974). The follow-up period varied from 2-5 years for 25 patients, 6-10 years for 24 patients, 11-15 years for 24 patients, 16-20 years for 19 patients, 21-25 years for 13 patients, 30-36 years for four patients.
In 13 patients (12%), RC emerged spontaneously and in 96 patients (88%), it was associated with antidepressant and other treatments. In 19 women (28% of all women) RC course started in perimenopausal age (45-54 years). The mean duration of RC during the follow-up period was 7.86 years (range 1-32) and its total duration (including RC course prior to the follow-up period) was 11 years (range 1-40). The total duration of the affective disorder, from the first episode to the end of the follow-up, was 21.78 years (range 1-70). At the end of the follow-up, 36 patients (33%) had complete remission for at least the past year, 44 (40%) stayed rapid cycling with severe episodes (six of this group committed suicide), while 15 (14%) were rapid cycling but with attenuated episodes. The other 14 patients (13%) became long cyclers, eight with severe episodes and six with milder ones. The main distinguishing features between those who remitted from and those who persisted in the RC course were: (1). the initial cycle pattern: patients with Depression-Hypomania(mania)-Free interval cycles (53 patients) had a worse outcome: 26.4% remitted and 52.8% persisted in the RC course through to the end of the follow up period. The Mania/Hypomania-Depression-Free interval cycles (22 patients) had a significantly better outcome, with 50% remitted and 27.2% persisting RC; and (2). the occurrence of the switch process from depression to hypomania/mania and the occurrence of agitated depressions made the prognosis worse. Continuous treatment was more effective against mania/hypomania than against depression, yet in all persisting RC cases the mania/hypomania remitted only partially.
These data derive from clinics known for their expertise in mood disorders, and they may have attracted and retained patients with a more severe course. Treatment was uncontrolled and consisted more of lithium than divalproex, lamotrigene and olanzapine, recently shown to be beneficial in subgroups of patients with rapid-cycling.
Our findings suggest that rapid cyclicity, spontaneous or induced, once established, becomes for many years a stable rhythm in a substantial proportion of patients, linked to endogenous and environmental factors. The suggestion is made to consider as rapid-cyclers, at least for research purposes, those patients who have had a rapid cycling course for at least 2 years, borrowing the duration criterion currently employed for other chronic disorders such as Dysthymia and Cyclothymia. That our patients had poorer prognosis than some other cohorts in the literature is probably due to the shorter duration of "rapid-cycling" at entry in the latter cohorts. A true understanding of the nature of rapid-cycling will require a rigorous definition of not only duration, but also pole-switching and course patterns at entry into study.
《精神疾病诊断与统计手册》第四版（DSM-IV）将快速循环作为一种病程说明予以认可，这引发了关于快速循环（RC）患者的稳定性及长期预后的问题。关于该主题的数据稀少且常常相互矛盾。据我们所知，这是首批对患者进行长期亲自跟踪研究的，直接涉及RC病程持续时间问题的研究。
我们对109例RC患者（68名女性和41名男性）的病程演变进行了研究，跟踪时间最短为2年，最长达36年，从作者（A.K., G.P.M., P.G., L.P., D.R.）诊断出RC病程的索引发作期开始。如果患者符合每年发作≥4次情感发作所定义的RC标准（Dunner和Fieve，1974年），则纳入本研究。25例患者的随访期为2 - 5年，24例为6 - 10年，24例为11 - 15年，19例为16 - 20年，13例为21 - 25年，4例为30 - 36年。
13例患者（12%）的RC为自发出现，96例患者（88%）的RC与抗抑郁药及其他治疗有关。19名女性（占所有女性的28%）的RC病程始于围绝经期（45 - 54岁）。随访期间RC的平均持续时间为7.86年（范围1 - 32年），其总持续时间（包括随访期之前的RC病程）为11年（范围1 - 40年）。从首次发作到随访结束，情感障碍的总持续时间为21.78年（范围1 - 70年）。随访结束时，36例患者（33%）至少在过去一年完全缓解，44例（40%）仍为快速循环且发作严重（该组中有6例自杀），而15例（14%）为快速循环但发作较轻。其他14例患者（13%）变为长周期循环者，8例发作严重，6例发作较轻。缓解者与持续处于RC病程者之间的主要区别特征为：（1）初始循环模式：具有抑郁 - 轻躁狂（躁狂） - 无发作间期循环的患者（53例）预后较差：26.4%缓解，52.8%在随访期结束时仍处于RC病程。具有躁狂/轻躁狂 - 抑郁 - 无发作间期循环的患者（22例）预后明显较好，50%缓解，27.2%仍为RC；（2）从抑郁转变为轻躁狂/躁狂的转换过程以及激越性抑郁的出现使预后更差。持续治疗对躁狂/轻躁狂比对抑郁更有效，但在所有持续的RC病例中，躁狂/轻躁狂仅部分缓解。
这些数据来自以情绪障碍专业知识闻名的诊所，可能吸引并留住了病程更严重的患者。治疗未设对照，且更多使用的是锂盐而非丙戊酸盐、拉莫三嗪和奥氮平，而最近研究表明这些药物对快速循环患者亚组有益。
我们的研究结果表明，快速循环，无论是自发的还是诱发的，一旦确立，在相当一部分患者中会在多年内成为一种稳定的节律，与内源性和环境因素相关。建议至少出于研究目的，将那些具有至少2年快速循环病程的患者视为快速循环者，借鉴目前用于其他慢性疾病如恶劣心境障碍和环性心境障碍的病程持续时间标准。我们的患者预后比文献中其他一些队列更差，可能是因为后者队列中“快速循环”开始时的持续时间较短。要真正理解快速循环的本质，不仅需要对病程持续时间进行严格定义，还需要对研究入组时的极性转换和病程模式进行严格定义。
