Antidepressants are in widespread use, but there is considerable variability in how patients respond, with some seeing substantial improvement while others respond only partially or not at all. In this podcast, Dr. Antonio E. Nardi discusses the many factors that underlie response rates, including psychological factors, personality traits, and medication adherence. There are also some mood conditions such as demoralization that may seem to resemble depression but do not meet all the clinical criteria. Recognizing these different emotional states is crucial for both individuals and clinicians in the treatment of low mood disorders. Dr. Nardi, along with Drs. Richard I. Shader, Richard Balon, Anthony J. Rothschild, and Larissa Junkes, are the authors of an editorial titled, " 'I am depressed': The many meanings that may underlie variability in response to antidepressants." The editorial is published in the September-October 2025 issue of the Journal of Clinical Psychopharmacology. doi: 10.1097/JCP.0000000000002053