The substantial non-response rate in depressive patients indicates a continuing need to identify predictors of treatment outcome. The aim of this 6-week, open-label study was (1) to compare the efficacy of a priori defined predictors: ≥20% reduction in MADRS score at week 1, ≥20% reduction in MADRS score at week 2 (RM ≥ 20% W2), decrease of cordance (RC), and increase of serum and plasma level of brain-derived neurotrophic factor at week 1; and (2) to assess whether their combination yields higher efficacy in the prediction of response to selective serotonin re-uptake inhibitors (SSRIs) than when used singly. Twenty-one patients (55%) achieved a response to SSRIs. The RM ≥20% W2 (areas under curve—AUC = 0.83) showed better predictive efficacy compared to all other predictors with the exception of RC. The identified combined model (RM ≥ 20% W2 + RC), which predicted response with an 84% accuracy (AUC = 0.92), may be a useful tool in the prediction of response to SSRIs.