--- - |2+ Background Definition of response is critical when seeking to establish valid predictors of treatment success. However, response at the end of study or endpoint only provides one view of the overall clinical picture that is relevant in testing for predictors. The current study employed a classification technique designed to group subjects based on their rate of change over time, while simultaneously addressing the issue of controlling for baseline severity. Methods A set of latent class trajectory analyses, incorporating baseline level of symptoms, were performed on a sample of 344 depressed patients from a clinical trial evaluating the efficacy of cognitive behavior therapy and two antidepressant medications (escitalopram and duloxetine) in patients with major depressive disorder. Results Although very few demographic and illness‐related features were associated with response rate profiles, the aggregated effect of candidate genetic variants previously identified in large pharmacogenetic studies and meta‐analyses showed a significant association with early remission as well as nonresponse. These same genetic scores showed a less compelling relationship with endpoint response categories. In addition, consistent nonresponse throughout the study treatment period was shown to occur in different subjects than endpoint nonresponse, which was verified by follow‐up augmentation treatment outcomes. Conclusions When defining groups based on the rate of change, controlling for baseline depression severity may help to identify the clinically relevant distinctions of early response on one end and consistent nonresponse on the other. - Depression and Anxiety, Volume 35, Issue 10, Page 992-1000, October 2018.