Post Robert M, Leverich Gabriele S, Nolen Willem A, Kupka Ralph W, Altshuler Lori L, Frye Mark A, Suppes Trisha, McElroy Susan, Keck Paul, Grunze Heinze, Walden Jorg
Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health, Biological Psychiatry Branch, Bethesda, MD 20892-1272, USA.
Bipolar Disord. 2003 Dec;5(6):396-406. doi: 10.1046/j.1399-5618.2003.00065.x.
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.
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 (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.
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.
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.
单药抗抑郁药（ADs）作为心境稳定剂辅助用药的风险效益比仍是该领域专家存在争议和分歧的一个方面。本文综述了与当前讨论和建议相关的新数据：（1）双相情感障碍中的抑郁，（2）ADs的转相率，以及（3）ADs停药风险。
在第一项综述研究中，对258例双相情感障碍门诊患者采用美国国立精神卫生研究所生活图表法（NIMH-LCM）进行为期1年的前瞻性每日评估。在第二项研究中，127例双相抑郁患者被随机分为接受10周的舍曲林、安非他酮或文拉法辛治疗，作为心境稳定剂的辅助用药；无反应者重新随机分组，有反应者接受为期1年的维持治疗。在最后一项研究中，阿尔茨舒勒等人回顾性和前瞻性地评估了在心境正常2个月后继续使用ADs的患者与停用ADs的患者相比，抑郁复发的风险。
尽管进行了强化自然主义治疗，但对258例双相情感障碍门诊患者进行为期1年的前瞻性随访发现，抑郁天数是躁狂天数的3倍，这再次强调了尽管有多种治疗选择，但双相情感障碍中仍存在相当严重的抑郁发病率。在将双相抑郁患者随机分为三种ADs之一的研究中，在对175例使用心境稳定剂联合ADs进行治疗的试验后，发现了一系列从轻度躁狂到躁狂转相的严重程度和持续时间。在为期10周的急性试验中，9.1%与转相至轻度躁狂或躁狂有关，另外9.1%与仅出现一周或更长时间的轻度躁狂（功能无至轻微障碍）有关。在73项维持期AD试验中，分别有16.4%和19.2%与轻度躁狂至躁狂和轻度躁狂转相类似相关。在阿尔茨舒勒等人的研究中，那些在任何一种AD上保持良好状态超过2个月（最初接受治疗者中仅15 - 20%）且继续使用ADs的患者，与停用ADs的患者相比，在1年中抑郁复发率较低（第一项和第二项研究中分别为35%和36%）。令人惊讶的是，与停用ADs的患者相比，继续使用ADs与转相至躁狂的发生率增加无关。
这些数据表明，在约三分之二接受强化治疗的双相情感障碍门诊患者中，抑郁和抑郁发作仍是一个严重问题。急性联合ADs治疗的有效率适中，18.2%转相至轻度躁狂或躁狂发作，35.6%的维持试验出现这两种转相类型。两项独立研究表明，在非常小的一个亚组中，即那些在ADs上保持良好状态至少2个月的患者，应考虑继续这种联合ADs的治疗，因为停用ADs似乎与随后一年抑郁复发风险大幅增加相关，且转相至躁狂的风险并未降低。
