Sage Therapeutics, Inc., Cambridge, MA, USA.
CenExel CNS, Los Alamitos, CA, USA.
J Psychopharmacol. 2024 Dec;38(12):1122-1136. doi: 10.1177/02698811241282777. Epub 2024 Oct 11.
Zuranolone is an oral, once-daily, 14-day treatment course approved for adults with postpartum depression in the United States.
To assess cognitive effects, pharmacokinetics, and safety of zuranolone, alone or with alprazolam/ethanol.
This was a phase 1, two-part, two-period, randomized, double-blind, placebo-controlled crossover trial. Participants received zuranolone 50 mg or placebo once daily for 9 days, and additionally received alprazolam (1 mg, Part A), ethanol (males: 0.7 g/kg; females: 0.6 g/kg, Part B), or corresponding placebo on days 1, 5, and 9. Within each part, participants received all treatment combinations. Cognition was assessed using a computerized test battery; pharmacokinetics and safety were also evaluated.
All participants (Part A, = 24; Part B, = 25) received ⩾1 dose of zuranolone/placebo. Compared to placebo, zuranolone produced small-to-moderate cognitive decline (Cohen's || = 0.126-0.76); effects were larger with alprazolam (Cohen's || = 0.523-0.93) and ethanol (Cohen's || = 0.345-0.88). Zuranolone coadministration with alprazolam (Cohen's || = 0.6-1.227) or ethanol (Cohen's || = 0.054-0.5) generally worsened cognitive decline when compared with zuranolone alone. Maximal pharmacodynamic effects occurred at approximately 5 h and were resolved by 12 h postbaseline. No pharmacokinetic interactions were observed. Incidence of adverse events was similar between groups; most events were mild or moderate in severity.
A general small-to-moderate magnitude decline in cognition occurred with zuranolone alone. Coadministration with alprazolam/ethanol increased the magnitude, but not the duration, of effects compared with single-agent administration. Zuranolone prescribers and patients should be aware of the potential for increased central nervous system-depressant effects if coadministered with GABAergic active compounds such as alprazolam and ethanol.
佐拉鲁肽是一种每日口服一次的 14 天疗程药物，已获美国批准用于治疗产后抑郁症成人患者。
评估佐拉鲁肽单独或与阿普唑仑/乙醇联合使用的认知影响、药代动力学和安全性。
这是一项为期 1 期、两部分、两周期、随机、双盲、安慰剂对照交叉试验。参与者每日接受佐拉鲁肽 50mg 或安慰剂，共 9 天，在第 1、5 和 9 天还分别接受阿普唑仑（1mg，第 A 部分）、乙醇（男性：0.7g/kg；女性：0.6g/kg，第 B 部分）或相应安慰剂。在每个部分内，参与者接受所有治疗组合。使用计算机化测试组合评估认知；还评估了药代动力学和安全性。
所有参与者（第 A 部分，n=24；第 B 部分，n=25）均接受了 ⩾1 剂佐拉鲁肽/安慰剂。与安慰剂相比，佐拉鲁肽引起的认知下降较小至中等程度（Cohen's ||=0.126-0.76）；与阿普唑仑（Cohen's ||=0.523-0.93）和乙醇（Cohen's ||=0.345-0.88）联合使用时作用更大。与佐拉鲁肽单独使用相比，佐拉鲁肽与阿普唑仑（Cohen's ||=0.6-1.227）或乙醇（Cohen's ||=0.054-0.5）联合使用通常会加重认知下降。最大药效动力学效应发生在大约 5 小时，在基线后 12 小时内得到解决。未观察到药代动力学相互作用。不良事件的发生率在各组之间相似；大多数事件的严重程度为轻度或中度。
单独使用佐拉鲁肽会导致认知能力出现小至中等程度的普遍下降。与单药治疗相比，与阿普唑仑/乙醇联合使用会增加效应的幅度，但不会延长效应的持续时间。如果与阿普唑仑和乙醇等 GABA 能活性化合物联合使用，佐拉鲁肽的开处方者和患者应注意中枢神经系统抑制剂作用增强的潜在风险。
