Using Digital Phenotyping to Discriminate Unipolar Depression and Bipolar Disorder: Systematic Review

Background Differentiating bipolar disorder (BD) from unipolar depression (UD) is essential, as these conditions differ greatly in their progression and treatment approaches. Digital phenotyping, which involves using data from smartphones or other digital devices to assess mental health, has emerged as a promising tool for distinguishing between these two disorders. Objective This systematic review aimed to achieve two goals: (1) to summarize the existing literature on the use of digital phenotyping to directly distinguish between UD and BD and (2) to review studies that use digital phenotyping to classify UD, BD, and healthy control (HC) individuals. Furthermore, the review sought to identify gaps in the current research and propose directions for future studies. Methods We systematically searched the Scopus, IEEE Xplore, PubMed, Embase, Web of Science, and PsycINFO databases up to March 20, 2025. Studies were included if they used portable or wearable digital tools to directly distinguish between UD and BD, or to classify UD, BD, and HC. Original studies published in English, including both journal and conference papers, were included, while reviews, narrative reviews, systematic reviews, and meta-analyses were excluded. Articles were excluded if the diagnosis was not made through a professional medical evaluation or if they relied on electronic health records or clinical data. For each included study, the following information was extracted: demographic characteristics, diagnostic criteria or psychiatric assessments, details of the technological tools and data types, duration of data collection, data preprocessing methods, selected variables or features, machine learning algorithms or statistical tests, validation, and main findings. Results We included 21 studies, of which 11 (52%) focused on directly distinguishing between UD and BD, while 10 (48%) classified UD, BD, and HC. The studies were categorized into 4 groups based on the type of digital tool used: 6 (29%) used smartphone apps, 3 (14%) used wearable devices, 11 (52%) analyzed audiovisual recordings, and 1 (5%) used multimodal technologies. Features such as activity levels from smartphone apps or wearable devices emerged as potential markers for directly distinguishing UD and BD. Patients with BD generally exhibited lower activity levels than those with UD. They also tended to show higher activity in the morning and lower in the evening, while patients with UD showed the opposite pattern. Moreover, speech modalities or the integration of multiple modalities achieved better classification performance across UD, BD, and HC groups, although the specific contributing features remained unclear. Conclusions Digital phenotyping shows potential in distinguishing BD from UD, but challenges like data privacy, security concerns, and equitable access must be addressed. Further research should focus on overcoming these challenges and refining digital phenotyping methodologies to ensure broader applicability in clinical settings. Trial Registration PROSPERO CRD42024624202; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024624202