Yeah, No Journal Club

Intranasal Esketamine and the Placebo Response

Episode Summary

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."

Episode Notes

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:

BT Walsh et al. Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing. JAMA 2002; 287(14):1840-1847.

W Rief et al . Meta-analysis of the Placebo Response in Antidepressant Trials. Journal of Affective Disorders 2009; 118:1-8.

TA Furukawa et al. Placebo Response Rates in Antidepressant Trials: A Systematic Review of Published and Unpublished Double-Blind Randomised Controlled Studies. Lancet Psychiatry 2016; 3:1059-1066.