Treatment-resistant depression (TRD) poses a significant societal challenge, with gender-specific treatment gaps. In a clinical trial targeting TRD, we introduced lifestyle-based interventions. Analyzing data from 24 men and 70 women with TRD, the current study aimed to assess gender-related efficacy differences. Descriptive and univariate analyses unveiled variations in sociodemographic and clinical factors. Utilizing repeated measures ANOVA while controlling for baseline values and age, results indicated a notable gender disparity. Specifically, women exhibited a significantly poorer progression of depressive symptoms. This underscores the need for tailored interventions addressing gender-specific nuances in TRD treatment.