Leverich Gabriele S, Altshuler Lori L, Frye Mark A, Suppes Trisha, McElroy Susan L, Keck Paul E, Kupka Ralph W, Denicoff Kirk D, Nolen Willem A, Grunze Heinz, Martinez Maria I, Post Robert M
Biological Psychiatry Branch, National Institutes of Mental Health, Bldg. 10/Room 3S239, 10 Center Drive, MSC-1272, Bethesda, MD 20892-1272, USA.
Am J Psychiatry. 2006 Feb;163(2):232-9. doi: 10.1176/appi.ajp.163.2.232.
The authors examined the comparative risks of switches in mood polarity into hypomania or mania during acute and continuation trials of adjunctive antidepressant treatment of bipolar depression.
One hundred fifty-nine patients with bipolar I disorder or bipolar II disorder participated in a total of 228 acute (10-week) randomized trials of bupropion, sertraline, or venlafaxine as an adjunct to a mood stabilizer. Patients in 87 of these trials entered continuation treatment for up to 1 year. Antidepressant response and the occurrence of subthreshold brief hypomania (emergence of brief hypomania [at least 1 but <7 days] or recurrent brief hypomania) and threshold switches (emergence of full-duration hypomania [> or =7 days] or mania) were blindly assessed by using clinician-rated daily reports of mood-associated dysfunction on the National Institute of Mental Health Life Chart Method.
Threshold switches into full-duration hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials. The rate of threshold switches was higher in the 169 trials in patients with bipolar I disorder (30.8%) than the 59 trials in patients with bipolar II disorder (18.6%). The ratio of threshold switches to subthreshold brief hypomanias was higher in both the acute (ratio=3.60) and continuation trials (ratio=3.75) of venlafaxine than in the acute and continuation trials of bupropion (ratios=0.85 and 1.17, respectively) and sertraline (ratios=1.67 and 1.66, respectively). In only 37 (16.2%) of the original 228 acute antidepressant trials, or in only 23.3% of the patients, was there a sustained antidepressant response in the continuation phase in the absence of a threshold switch.
Adjunctive treatment with antidepressants in bipolar depression was associated with substantial risks of threshold switches to full-duration hypomania or mania in both acute and long-term continuation treatment. Of the three antidepressants included in the study, venlafaxine was associated with the highest relative risk of such switching and bupropion with the lowest risk.
作者在双相抑郁辅助抗抑郁治疗的急性期和延续期试验中，研究了情绪极性转换为轻躁狂或躁狂的相对风险。
159例双相I型障碍或双相II型障碍患者参与了总共228项为期10周的安非他酮、舍曲林或文拉法辛作为心境稳定剂辅助治疗的急性随机试验。其中87项试验中的患者进入了长达1年的延续治疗。使用美国国立精神卫生研究所生活图表法中临床医生评定的与情绪相关功能障碍的每日报告，对抑郁反应以及阈下短暂轻躁狂（短暂轻躁狂发作[至少1天但<7天]或反复短暂轻躁狂发作）和阈上转换（持续时间完整的轻躁狂发作[≥7天]或躁狂发作）的发生情况进行盲法评估。
在急性治疗试验中，分别有11.4%和7.9%的患者出现了持续时间完整的轻躁狂发作和躁狂发作的阈上转换；在延续期试验中，这一比例分别为21.8%和14.9%。双相I型障碍患者的169项试验中的阈上转换率（30.8%）高于双相II型障碍患者的59项试验（18.6%）。与安非他酮（分别为0.85和1.17）和舍曲林（分别为1.67和1.66）的急性和延续期试验相比，文拉法辛的急性（比值=3.60）和延续期试验（比值=3.75）中阈上转换与阈下短暂轻躁狂的比例更高。在最初的228项急性抗抑郁试验中，只有37项（16.2%），或仅23.3%的患者在延续期出现了持续的抗抑郁反应且未发生阈上转换。
双相抑郁的抗抑郁辅助治疗在急性和长期延续治疗中均与转换为持续时间完整的轻躁狂或躁狂的阈上转换的重大风险相关。在该研究纳入的三种抗抑郁药中，文拉法辛发生此类转换的相对风险最高，安非他酮风险最低。
