Prospective associations of multimodal serum biomarkers with 12-week and 12-month remission in patients with depressive disorders receiving stepwise psychopharmacotherapy

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. They received initial antidepressant monotherapy followed, as required by a protocol of successive alternative pharmacological strategies administered in 3-week steps during the acute (3-12 week) phase (N = 1086), and in 3month steps during the continuation (6-12 month) phase (N = 884). Remission was defined as a Hamilton Depression Rating Scale score of <= 7. Remission was achieved in 490 (45.1%) over the 12-week, and in 625 (70.7%) over the 12-month, treatment periods. Combination scores of four serum biomarkers (high-sensitivity Creactive protein, interleukin-1 beta, interleukin-6, and leptin) were prospectively associated with 12-week remission; and four (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, and brain-derived neurotrophic factor) were prospectively associated with 12-month remission in a clear gradient manner (P-values < 0.001) and after adjustment for relevant covariates. These associations were evident after the Step 1 treatment monotherapy but weakened with increasing treatment steps, falling below statistical significance after 4 + treatment steps. Application of combined multiple serum biomarkers, particularly on inflammatory markers, could improve predictability of remission at acute and continuation treatment phases for depressive disorders. Patients with unfavourable biomarkers might require alternative treatment regimes for better outcomes.

Automated summary

This study investigated the association between serum biomarkers and treatment outcomes in depression. The findings suggest that certain serum biomarkers are prospectively associated with remission at 12-week and 12-month periods. Inflammatory markers, in particular, show good predictability for remission, but the association weakens with increasing treatment steps.