The increasing prescription of antidepressants (ATDs) has led to their widespread detection worldwide. Among these, amitriptyline (AMI) and melitracen (MEL) are particularly problematic due to their high toxicity and low removal efficiency in conventional wastewater treatment. Biotic transformation products (TPs) of AMI are largely unexplored due to limited biodegradation reported. For MEL, environmental fate studies remain scarce, leaving potential TPs from both biotic and abiotic processes unexplored. This study investigates the transformation and fate of AMI, MEL, and their TPs during biological treatment and ozonation processes. Complete removal of AMI was achieved through adsorption and biodegradation, whereas MEL exhibited only partial removal (75 ± 15 %), predominantly through sludge adsorption. In addition to the well-known TP nortriptyline, two new biotic TPs for AMI and one for MEL were identified. Ozonation resulted in the formation of six TPs for AMI and four for MEL, with partial removal (<55 %) of both ATDs. Toxicity predictions indicated that TPs exhibited toxicity levels comparable to the parent compounds for aquatic organisms. Notably, four of the newly identified TPs of AMI and MEL were also detected in real effluent samples from full-scale treatment plants. Laboratory-scale granular activated carbon (GAC) treatment of unspiked effluent proved to be an effective tertiary treatment method for the removal (>94 %) of AMI, MEL, and their TPs.