Department of Medical Pharmacology, Faculty of Medicine, Gaziantep Islam Science and Technology University, 27010, Gaziantep, Turkey.
Department of Physiology, Faculty of Medicine, Gaziantep University, 27310 Gaziantep, Turkey.
Ideggyogy Sz. 2024 Jul 30;77(7-8):227-235. doi: 10.18071/isz.77.0227.
Depression, anxiety and psychotic disorders are common perinatal mental health disorders in the postpartum period. Depressive symptoms that occur postpartum are also present in the prenatal period in 50% of patients. Risk factors for the development of postpartum depression include poor relationship with the partner, lack of social support, mother’s low socioeconomic status and multiparity. It has been determined that reproductive hormones change significantly during peripartum. Progesterone is one of these hormones and acts on the central nervous system starting from the fetal period; neurogenesis, neuromodulation, sedation are some of these effects. It has also been observed that progesterone has positive effects on learning, memory and mood. Progesterone exerts its effects on the central nervous system by converting into its metabolite allopregnanolone. Allopregnanolone is one of the neuroactive steroids, and found in similar amounts in the circulation of pregnant women and fetuses. It acts on synaptic and extrasynaptic γ-aminobutyric acid type A (GABAA) receptors and is a positive allosteric modulator of the GABAA receptor. Allopregnanolone increases both the receptor’s opening frequency and its open duration and improves GABAergic current. Low serum allopregnanolone levels in the second trimester are predictive of postpartum depression. Each 1 ng/mL increase in serum allopregnanolone level reduces the risk of development of postpartum depression by 63%. Brexanolone and zuranolone are synthetic allopregnanolone preparations approved by the FDA for use in female patients with postpartum depression. They act via positive allosteric modulation on the GABAA receptor. Brexanolone is administered via intravenous infusion at varying infusion rates in a healthcare facility over 60 hours. Its effect starts immediately after treatment and continues until the 30th day of follow-up, and depressive mood does not recur. Zuranolone was developed for oral use, and administered as a single dose of 50 mg after a fatty meal. Their effectiveness has been demonstrated in patients with treatment-resistant depression. The development of other novel agents that act on the GABAA receptor and other pathways for the treatment of postpartum depression is in progress.
.抑郁、焦虑和精神病障碍是产后期间常见的围产期心理健康障碍。产后出现的抑郁症状在 50%的患者中也存在于产前。产后抑郁症的发展风险因素包括与伴侣关系不佳、缺乏社会支持、母亲社会经济地位低和多产。已经确定，生殖激素在围产期会发生显著变化。孕酮就是其中一种激素，从胎儿期开始作用于中枢神经系统；神经发生、神经调节、镇静是其中一些作用。也观察到孕酮对学习、记忆和情绪有积极影响。孕酮通过转化为其代谢物别孕烯醇酮在中枢神经系统中发挥作用。别孕烯醇酮是神经活性甾体之一，在孕妇和胎儿的循环中含量相似。它作用于突触和 extrasynaptic γ-氨基丁酸 A 型（GABAA）受体，是 GABAA 受体的正变构调节剂。别孕烯醇酮增加受体的开放频率和开放持续时间，并改善 GABA 能电流。孕中期血清别孕烯醇酮水平低可预测产后抑郁症。血清别孕烯醇酮水平每增加 1ng/ml，产后抑郁症的发展风险降低 63%。Brexanolone 和 zuranolone 是美国食品和药物管理局批准用于产后抑郁症女性患者的合成别孕烯醇酮制剂。它们通过 GABAA 受体的正变构调节起作用。Brexanolone 通过静脉输注在医疗机构中以不同的输注速率给药，持续 60 小时。治疗后立即起效，持续至随访第 30 天，且抑郁情绪不再复发。Zuranolone 为口服制剂，在高脂肪餐后给予 50mg 单剂量。它们在治疗抵抗性抑郁症患者中已显示出有效性。正在开发其他作用于 GABAA 受体和其他途径的新型药物，用于治疗产后抑郁症。
