The DEXA-PSYCH Study-dexamethasone for moderate-to-severe depression: study protocol for a double-blind, randomized, parallel-group, placebo-controlled trial.

Abstract

Background: 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.

Methods: 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.

Discussion: 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.

Trial registration: 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.