Challenges and future directions of Transcranial Direct Current Stimulation for Depression: insights from a systematic review and meta-analysis

Depression is a common and debilitating disorder affecting millions. First-line treatments fail to achieve remission in about one-third of patients, highlighting a critical treatment need. Transcranial direct current stimulation (tDCS) has emerged as a novel treatment for depression. Therefore, the aim of this review was to provide a comprehensive overview of the last decade of tDCS trials for depression and propose future research directions. To compile studies of the past decade, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) of tDCS for depression. A total of 21 RCTs were included, presenting a moderate effect for active tDCS compared to placebo. We also provided a description of study designs, stimulation parameters, and patients' characteristics. Following, we proposed possible strategies to enhance clinical effectiveness and reduce variability in results, including 1) optimization/personalization of tDCS via spatial and temporal target localization; 2) optimized methodological strategies, including home-based, accelerated tDCS protocols and novel trial designs; and 3) investigate patient profile to identify features that can predict treatment response. In conclusion, tDCS holds promise as a treatment for depression, but variability in trial parameters and outcomes underscores the need for its further optimization. Refining and standardizing protocols may enhance its effectiveness.