Department of Psychiatry, Women's Behavioral Health, Zucker Hillside Hospital, Northwell Health, 75-59 263rd Street, New York, NY, 11004, USA.
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
CNS Drugs. 2019 Mar;33(3):265-282. doi: 10.1007/s40263-019-00605-7.
Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cognitive, behavioral, and emotional development with lasting consequences. There are a number of therapeutic interventions for postpartum depression including pharmacotherapy, psychotherapy, neuromodulation, and hormonal therapy among others, most of which have been adapted from the treatment of major depressive disorder outside of the peripartum period. Current evidence of antidepressant treatment for postpartum depression is limited by the small number of randomized clinical trials, underpowered samples, and the lack of long-term follow-up. The peripartum period is characterized by rapid and significant physiological change in plasma levels of endocrine hormones, peptides, and neuroactive steroids. Evidence supporting the role of neuroactive steroids and γ-aminobutyric acid (GABA) in the pathophysiology of postpartum depression led to the investigation of synthetic neuroactive steroids and their analogs as potential treatment for postpartum depression. Brexanolone, a soluble proprietary intravenous preparation of synthetic allopregnanolone, has been developed. A recent series of open-label and placebo-controlled randomized clinical trials of brexanolone in postpartum depression demonstrated a rapid reduction in depressive symptoms, and has led to the submission for regulatory approval to the US Food and Drug Administration (decision due in March 2019). SAGE-217, an allopregnanolone analog, with oral bioavailability, was recently tested in a randomized, double-blind, placebo-controlled phase III study in severe postpartum depression, with reportedly positive results. Finally, a 3β-methylated synthetic analog of allopregnanolone, ganaxolone, is being tested in both intravenous and oral forms, in randomized, double-blind, placebo-controlled phase II studies in severe postpartum depression.
产后抑郁症是分娩后最常见的并发症之一。未经治疗的产后抑郁症会对母婴的健康产生重大的负面影响，对儿童的认知、行为和情绪发展产生负面影响，并产生持久的后果。产后抑郁症有许多治疗干预措施，包括药物治疗、心理治疗、神经调节和激素治疗等，其中大多数都源自于非围产期重度抑郁症的治疗。目前，抗抑郁药治疗产后抑郁症的证据受到随机临床试验数量少、样本量不足以及缺乏长期随访的限制。围产期的特点是内分泌激素、肽和神经活性甾体的血浆水平迅速显著变化。支持神经活性甾体和γ-氨基丁酸（GABA）在产后抑郁症发病机制中的作用的证据，导致了对合成神经活性甾体及其类似物作为产后抑郁症潜在治疗方法的研究。Brexanolone 是一种合成的全异戊烯醇酮的可溶性专有静脉制剂，已经开发出来。最近一系列关于产后抑郁症 Brexanolone 的开放标签和安慰剂对照随机临床试验显示，其可迅速减轻抑郁症状，并已向美国食品和药物管理局（2019 年 3 月做出决定）提交监管批准申请。具有口服生物利用度的全异戊烯醇酮类似物 SAGE-217，最近在一项严重产后抑郁症的随机、双盲、安慰剂对照 III 期研究中进行了测试，据称结果为阳性。最后，一种 3β-甲基化的全异戊烯醇酮合成类似物 ganaxolone，正在严重产后抑郁症的静脉内和口服形式的随机、双盲、安慰剂对照 II 期研究中进行测试。
