Figure 2.

Proposed design for a pilot investigation of esketamine with Acceptance and Commitment Therapy (ACT) for treatment-resistant depression. Current esketamine dosing protocols call for twice weekly dosing during a 4-week induction phase, followed by weekly dosing during a maintenance phase in weeks 5 through 8. Patients receive an initial dose of 56 mg, followed by repeated doses of 56 mg or 84 mg based on treatment response (i.e., efficacy and tolerability). After initial study procedures, participants will be randomized to receive treatment as usual (plain circle) or esketamine in conjunction with ACT (circle with bracketed line) during the induction phase of treatment. Both study arms will follow the same clinical procedures for maintenance treatment and subsequent follow-up.