Ahmad Abdullah, Awan Abdul Rafeh, Nadeem Natasha, Javed Aamir Shahid, Farooqi Mobeen, Daniyal Muhammed, Mumtaz Hassan
CMH Lahore Medical College, National University of Medical Sciences, Lahore, Pakistan.
Department of Medicine, Nishtar Medical University, Multan, Pakistan.
Front Neurosci. 2024 Apr 25;18:1361692. doi: 10.3389/fnins.2024.1361692. eCollection 2024.
Current treatment modalities for Major Depressive Disorder have variable efficacies and a variety of side effects. To amend this, many trials for short term, well tolerated monotherapies are underway. One such option is Zuranolone (SAGE-217), which is a recent FDA approved antidepressant for depression (PPD) and is undergoing clinical trials for PPD, major depressive disorder (MDD) and essential tremors (ET).
Pool currently available data that compare Zuranolone to Placebo for the treatment of Major Depressive Disorder and evaluate its efficacy and safety profile.
We retrieved data from PUBMED and SCOPUS from inception to July 2023. We included articles comparing Zuranolone or SAGE 217 with placebo in patients suffering from Major Depressive Disorder. Review Manager 5.4 was used to analyze the outcomes including changes in the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline as well as any treatment emergent adverse events (TEAEs) and severe adverse events.
Our review analyzed 4 trials and the data of 1,357 patients. Patients treated with Zuranolone indicated a statistically significant effect in the change from baseline in HAM-D score ( = 0.0009; MD [95% CI]: -2.03 [-3.23, -0.84]) as well as in MADRS score ( = 0.02; MD [95% CI]: -2.30[-4.31, -0.30]) and HAM-A score ( = 0.03; MD [95% CI]: -1.41[-2.70, -0.11]) on 15th day when compared to the Placebo group. Zuranolone was also significantly associated with a higher response rate ( = 0.0008; OR [95% CI]: 1.63[1.14, 2.35]) and higher remission rate ( = 0.03; OR [95% CI]: 1.65[1.05, 2.59]) when compared with the placebo. As for safety, Zuranolone was significantly associated with 1 or more TEAE ( = 0.006; RR [95% CI]: 1.14[1.04, 1.24]) but an insignificant association with side effects that lead to drug discontinuation ( = 0.70; RR [95% CI]: 1.18[0.51, 2.76]) and serious adverse events ( = 0.48; RR [95% CI]: 1.46 [0.52, 4.10]) when compared with placebo.
Zuranolone is an effective and safe drug for short course major depressive disorder monotherapy. It shows results in 14 days (compared to 2-4 weeks that SSRI's take) and has anti-anxiolytic effects as well. However, only 4 trials have been used for the analysis and the sample size was small. The trials reviewed also cannot determine the long-term effects of the drug. More trials are needed to determine long term effects.
目前用于治疗重度抑郁症的方法疗效各异，且有多种副作用。为改善这一情况，许多针对短期、耐受性良好的单一疗法的试验正在进行。其中一种选择是祖拉诺酮（SAGE - 217），它是美国食品药品监督管理局（FDA）最近批准用于产后抑郁症（PPD）的抗抑郁药，目前正在进行针对产后抑郁症、重度抑郁症（MDD）和特发性震颤（ET）的临床试验。
汇总目前可用的将祖拉诺酮与安慰剂对比治疗重度抑郁症的数据，并评估其疗效和安全性。
我们检索了从创刊至2023年7月的PubMed和Scopus数据库中的数据。我们纳入了比较祖拉诺酮或SAGE 217与安慰剂治疗重度抑郁症患者的文章。使用Review Manager 5.4分析结果，包括汉密尔顿抑郁量表（HAM - D）、汉密尔顿焦虑量表（HAM - A）和蒙哥马利 - 阿斯伯格抑郁量表（MADRS）从基线开始的变化分数，以及任何治疗中出现的不良事件（TEAE）和严重不良事件。
我们的综述分析了4项试验和1357名患者的数据。与安慰剂组相比，接受祖拉诺酮治疗的患者在第15天时，HAM - D评分从基线的变化（P = 0.0009；MD[95%CI]：-2.03[-3.23，-0.84]）、MADRS评分（P = 0.02；MD[95%CI]：-2.30[-4.31，-0.30]）和HAM - A评分（P = 0.03；MD[95%CI]：-1.41[-2.70，-0.11]）上显示出统计学上的显著效果。与安慰剂相比，祖拉诺酮还与更高的缓解率（P = 0.0008；OR[95%CI]：1.63[1.14，2.35]）和更高的治愈率（P = 0.03；OR[95%CI]：1.65[1.05，2.59]）显著相关。至于安全性，与安慰剂相比，祖拉诺酮与1种或更多种治疗中出现的不良事件显著相关（P = 0.006；RR[95%CI]：1.14[1.04，1.24]），但与导致停药的副作用（P = 0.70；RR[95%CI]：1.18[0.51，2.76]）和严重不良事件（P = 0.48；RR[95%CI]：1.46[0.52，4.10]）的相关性不显著。
祖拉诺酮是一种用于短期重度抑郁症单一疗法的有效且安全的药物。它在14天内显示出效果（相比之下，选择性5 - 羟色胺再摄取抑制剂[SSRI]需要2 - 4周），并且也有抗焦虑作用。然而，仅4项试验用于分析且样本量较小。所审查的试验也无法确定该药物的长期效果。需要更多试验来确定其长期效果。
