Department of Psychiatry, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Department of Psychiatry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
BMC Neurol. 2024 Jun 6;24(1):190. doi: 10.1186/s12883-024-03683-3.
Post-stroke depression (PSD) is a significant impediment to successful rehabilitation and recovery after a stroke. Current therapeutic options are limited, leaving an unmet demand for specific and effective therapeutic options. Our objective was to investigate the safety of Maraviroc, a CCR5 antagonist, as a possible mechanism-based add-on therapeutic option for PSD in an open-label proof-of-concept clinical trial.
We conducted a 10-week clinical trial in which ten patients with subcortical and cortical stroke, suffering from PSD. were administered a daily oral dose of 300 mg Maraviroc. Participants were then monitored for an additional eight weeks. The primary outcome measure was serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. The secondary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS).
Maraviroc was well tolerated, with no reports of serious adverse events or discontinuations due to intolerance. The MADRS scores substantially reduced from baseline to week 10 (mean change: -16.4 ± 9.3; p < 0.001). By the conclusion of the treatment phase, a favorable response was observed in five patients, with four achieving remission. The time to response was relatively short, approximately three weeks. After the cessation of treatment, MADRS scores increased at week 18 by 6.1 ± 9.6 points (p = 0.014).
Our proof-of-concept study suggests that a daily dosage of 300 mg of Maraviroc may represent a well-tolerated and potentially effective pharmacological approach to treating PSD. Further comprehensive placebo-controlled studies are needed to assess the impact of Maraviroc augmentation on PSD.
ClinicalTrials.gov Identifier: NCT05932550, Retrospectively registered: 28/06/2023.
脑卒中后抑郁（PSD）是脑卒中后成功康复和恢复的重大障碍。目前的治疗选择有限，因此需要特定且有效的治疗选择。我们的目的是在一项开放标签的概念验证临床试验中研究 Maraviroc（一种 CCR5 拮抗剂）作为 PSD 可能的基于机制的附加治疗选择的安全性。
我们进行了一项为期 10 周的临床试验，纳入了 10 名患有皮质下和皮质脑卒中并患有 PSD 的患者，给予每日口服 Maraviroc 300mg。然后对参与者进行了额外的 8 周监测。主要终点是严重治疗后出现的不良事件（TEAEs）和因不耐受而导致停药的 TEAEs。次要终点是蒙特利尔抑郁评定量表（MADRS）的变化。
Maraviroc 耐受性良好，无严重不良事件报告，也无因不耐受而停药的报告。MADRS 评分从基线到第 10 周显著降低（平均变化：-16.4±9.3；p<0.001）。在治疗阶段结束时，有 5 名患者观察到良好的反应，其中 4 名患者达到缓解。反应时间相对较短，约为 3 周。治疗结束后，MADRS 评分在第 18 周增加了 6.1±9.6 分（p=0.014）。
我们的概念验证研究表明，每日 300mg Maraviroc 可能代表一种耐受良好且潜在有效的治疗 PSD 的药理学方法。需要进一步进行全面的安慰剂对照研究，以评估 Maraviroc 增强对 PSD 的影响。
ClinicalTrials.gov 标识符：NCT05932550，回顾性注册：2023 年 6 月 28 日。
