Despite decades of randomized-controlled trials demonstrating the efficacy of cognitive-behavior therapy (CBT), the mechanisms by which CBT achieves its effects remain unclear. Here, we describe how one adaptive intervention, the sequential multiple assignment randomized trial (SMART), can be used to randomize patients at multiple decision points in treatment to draw stronger causal claims about mechanisms unfolding in the course of CBT. We illustrate this design using preliminary data and case examples from an ongoing SMART in which we are testing the role of aversive reactions to negative emotions as a hypothesized mechanism of change in the Unified Protocol. Finally, we address common concerns with SMARTs and highlight how mechanistic research serves to personalize and optimize the delivery of CBT
