Abstract:The global rise in depression necessitates innovative detection methods for early intervention. Social media provides a unique opportunity to identify depression through user-generated posts. This systematic review evaluates machine learning (ML) models for depression detection on social media, focusing on biases and methodological challenges throughout the ML lifecycle. A search of PubMed, IEEE Xplore, and Google Scholar identified 47 relevant studies published after 2010. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was utilized to assess methodological quality and risk of bias. Significant biases impacting model reliability and generalizability were found. There is a predominant reliance on Twitter (63.8%) and English-language content (over 90%), with most studies focusing on users from the United States and Europe. Non-probability sampling methods (approximately 80%) limit representativeness. Only 23% of studies explicitly addressed linguistic nuances like negations, crucial for accurate sentiment analysis. Inconsistent hyperparameter tuning was observed, with only 27.7% properly tuning models. About 17% did not adequately partition data into training, validation, and test sets, risking overfitting. While 74.5% used appropriate evaluation metrics for imbalanced data, others relied on accuracy without addressing class imbalance, potentially skewing results. Reporting transparency varied, often lacking critical methodological details. These findings highlight the need to diversify data sources, standardize preprocessing protocols, ensure consistent model development practices, address class imbalance, and enhance reporting transparency. By overcoming these challenges, future research can develop more robust and generalizable ML models for depression detection on social media, contributing to improved mental health outcomes globally.