Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Corentin-Celton, Service de Psychiatrie, Issy-les-Moulineaux, France.
PLoS One. 2013;8(2):e55448. doi: 10.1371/journal.pone.0055448. Epub 2013 Feb 6.
Growing evidence supports the validity of distinguishing major depressive disorder (MDD) plus a lifetime history of subthreshold hypomania (D(m)) from pure MDD in psychiatric classifications. The present study sought to estimate the proportion of individuals with D(m) that would have been included in RCTs for MDD using typical eligibility criteria, and examine the potential impact of including these participants on internal validity.
Data were derived from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a national representative sample of 43,093 adults of the United States population. We examined the proportion of participants with a current diagnosis of pure MDD and D(m) that would have been eligible in clinical trials for MDD with a traditional set of eligibility criteria, and compared it with that of participants with bipolar 2 disorder if the same set of eligibility criteria was applied. We considered 4 models including different definitions of subthreshold hypomania.
We found that more than 7 out of ten participants with pure MDD and with D(m) would have been excluded by at least one classical eligibility criterion. Prevalence rate of individuals with D(m) in RCTs for MDD with traditional eligibility criteria would have ranged from 7.98% to 22.59%. Overall exclusion rate of individuals with MDD plus at least 4 lifetime concomitant hypomanic probes significantly differ from those with pure MDD, whereas it was not significantly different in those with at least 2 lifetime concomitant hypomanic probes compared to those with bipolar 2 disorder.
The current design of clinical trials for MDD may suffer from impaired external validity and potential impaired internal validity, due to the inclusion of a substantial proportion of individuals with subthreshold hypomania presenting with similar pattern of exclusion rates to those with bipolar 2 disorder, possibly resulting in a selection bias.
越来越多的证据支持在精神疾病分类中区分重性抑郁障碍（MDD）加终生亚临床轻躁狂史（D(m)）与单纯 MDD 的有效性。本研究旨在根据典型纳入标准，估计 D(m)患者在 MDD 的 RCT 中所占比例，并研究纳入这些患者对内部有效性的潜在影响。
数据来自于 2001-2002 年美国全国酒精相关情况和流行病学调查（NESARC），这是一个针对美国人口的 43093 名成年人的全国代表性样本。我们研究了当前患有单纯 MDD 和 D(m)的参与者，根据传统的一套纳入标准，在 MDD 的临床试验中符合条件的比例，并将其与同样适用该套纳入标准的双相 2 型障碍患者进行比较。我们考虑了 4 种不同的亚临床轻躁狂定义模型。
我们发现，超过十分之七的单纯 MDD 和 D(m)患者将至少被一个经典的纳入标准排除。用传统的纳入标准，在 MDD 的 RCT 中，D(m)患者的患病率将在 7.98%至 22.59%之间。MDD 加至少 4 次终生伴随轻躁狂探针的患者总体排除率与单纯 MDD 患者显著不同，而至少 2 次终生伴随轻躁狂探针的患者与双相 2 型障碍患者的排除率无显著差异。
由于包括了相当一部分有亚临床轻躁狂的患者，这些患者的排除率与双相 2 型障碍患者相似，目前 MDD 的临床试验设计可能存在外部有效性受损和潜在内部有效性受损的问题，这可能导致选择偏倚。
