Rømer Troels Boldt, Frederiksen Camilla Gøtzsche, Hansen Pernille Bølling, Christensen Rune Haubo Bojesen, Benros Michael Eriksen
Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Trials. 2025 Aug 25;26(1):303. doi: 10.1186/s13063-025-08989-2.
Globally, depression represents one of the leading causes of years lived with disability. The effects of current pharmacological treatments are small-to-moderate and often delayed by weeks. Immunological disturbances have been associated with depression and meta-analyses have suggested that anti-inflammatory agents have moderate-to-large anti-depressant effects. The largest effects were reported for glucocorticoids. However, previous trials were too small to legitimize standard use of glucocorticoids as add-on treatment in depression. The purpose of the DEXA-PSYCH study is to investigate the effect and safety of short-term, oral dexamethasone compared to placebo as add-on therapy in moderate-to-severe depression.
The DEXA-PSYCH trial is an investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group superiority trial. Three-hundred participants meeting criteria for moderate-to-severe depression will be randomized in a 1:1 ratio to 1 week of either dexamethasone (4 mg/day for 4 days, subsequently 2 mg/day for 3 days) or placebo as add-on treatment to treatment as usual. Both in- and out-patients are eligible. Exclusion criteria include, but are not limited to, psychotic disorders, bipolar disorder, and diabetes. The primary outcome is change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score on day 7 and will be analyzed through a Mixed Model for Repeated Measurements (MMRM) in an intention-to-treat analysis. Key secondary outcomes include response and remission rates, efficacy 3 weeks after the intervention, effects on quality of life, and safety outcomes. Other secondary outcomes include overall functioning, fatigue, anxiety, labor-market affiliation, and associations between inflammatory biomarkers and treatment response.
The DEXA-PSYCH trial represents the largest trial of its kind globally. If the trial confirms findings from previous, smaller studies, short-term oral dexamethasone could become an attractive augmentation strategy if acute anti-depressant effects are warranted. Dexamethasone is an off-patent, well-known drug readily repurposed for new indications.
EU Clinical Trials Number 2022-501428-45-00, Registered 25th of July 2022 in the EU Clinical Trials Information System ( https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2022-501428-45-00 ). WHO Universal Trial Identifier U1111-1280-7614.
在全球范围内，抑郁症是导致残疾生存年数的主要原因之一。目前的药物治疗效果较小至中等，且往往会延迟数周。免疫紊乱与抑郁症有关，荟萃分析表明抗炎药具有中等至较大的抗抑郁作用。糖皮质激素的效果最为显著。然而，先前的试验规模太小，无法使糖皮质激素作为抑郁症附加治疗的标准用法合法化。DEXA - PSYCH研究的目的是调查短期口服地塞米松与安慰剂相比，作为中度至重度抑郁症附加治疗的效果和安全性。
DEXA - PSYCH试验是一项由研究者发起的、双盲、随机、安慰剂对照、平行组优效性试验。300名符合中度至重度抑郁症标准的参与者将按1:1的比例随机分为两组，一组接受1周的地塞米松治疗（4毫克/天，共4天，随后2毫克/天，共3天），另一组接受安慰剂作为常规治疗的附加治疗。门诊患者和住院患者均符合条件。排除标准包括但不限于精神障碍、双相情感障碍和糖尿病。主要结局是第7天蒙哥马利 - 阿斯伯格抑郁评定量表（MADRS）评分相对于基线的变化，并将在意向性分析中通过重复测量混合模型（MMRM）进行分析。关键次要结局包括缓解率和治愈率、干预3周后的疗效、对生活质量的影响以及安全性结局。其他次要结局包括整体功能、疲劳、焦虑、劳动力市场参与度以及炎症生物标志物与治疗反应之间的关联。
DEXA - PSYCH试验是全球同类试验中规模最大的。如果该试验证实了先前较小规模研究的结果，那么在有急性抗抑郁作用的情况下，短期口服地塞米松可能会成为一种有吸引力的强化治疗策略。地塞米松是一种已过专利保护期的知名药物，很容易被重新用于新的适应症。
欧盟临床试验编号2022 - 501428 - 45 - 00，于欧盟临床试验信息系统（https://euclinicaltrials.eu/search - for - clinical - trials/?lang = en&EUCT = 2022 - 501428 - 45 - 00）于2022年7月25日注册。世界卫生组织通用试验标识符U1111 - 1280 - 7614。
