A Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD): study protocol for a randomized clinical trial

Background: Major depressive disorder (MDD) with atypical features, namely depression with atypical features (AFD), is one of the most common clinical specifiers of MDD, characterized by high risk of converting to bipolar disorder (BD). However, there is still lack of clinical guidelines for the diagnosis, treatment, and prognosis of AFD. Our study mainly focuses on three issues about what’s the objective endophenotype of AFD, how to select appropriate personalized treatment for AFD, what’s the predictive biomarkers of conversion to BD. Methods: The Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD) is a multicenter, prospective study consisting of a 12-week randomized-intervention trial followed by a real-world follow-up until 4 years or reaching the study endpoint. It is enrolling 480 patients with AFD (120 per treatment arm), 100 patients with BD, and 100 healthy controls (HC). Multivariate-dimension information is collected including clinical features, cognitive function, kynurenine pathway metabolomics, and multimodal magnetic resonance imaging (MRI) data. The iDoT-AFD study can be classified into three parts including the cross-sectional part and the prospective part. Firstly, multivariate informatics analyzes are performed to recognize patients with AFD from participants including the first-episode and recurrent atypical depression, patients with BD and HC. Secondly, patients with atypical depression are randomly allocated to one of the four treatment groups including ‘single application of selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI)’, ‘SSRI/SNRI combined with mood stabilizer’, ‘SSRI/SNRI combined with quetiapine (≥ 150mg/d)’, or ‘treatment as usual (TAU)’, and then followed up 12 weeks to find out the optimized treatment strategies. Thirdly, patients with atypical depression are followed up in the real world until 4 years or switching to BD to explore risk factors of conversion from atypical depression to BD and build the conversion risk early-warning model eventually. Discussion: First enrolment was in August 2019, and the recruitment is ongoing. The iDoT-AFD study explores clinical and biological markers for the diagnosis, treatment, and prognosis of AFD, and further provide evidence for clinical guidelines of this depressive specifier which has high risk switching to BD. Trial registration Clinical Trials.gov ID: NCT04209166. Registered on December 19, 2019.