Join us on a wild ride through the "registration trial" for intranasal esketamine. We work on understanding why this phase 3 trial was done in 3 phases. We focus in on placebo responding in antidepressant trials and why this is such an important piece of new medication development and FDA approval. Along the way, we rant a bit about the difference between "active control" and "augmentation."
The paper we discuss in this episode is V Popova et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined with a Newly Initiated Oral Antidepressant in Treatment Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry 2019; 176(6): 428-438.
For a deeper understanding of the factors that contribute to placebo response, check out BR Rutherford and SP Roose. A Model of Placebo Response in Antidepressant Clinical Trials. Am J Psychiatry 2013; 170:723-733.
Lots of data about the placebo response in antidepressant clinical trials: