Stepwise interventional psychiatry approach for major depression: A case series

Abstract

Introduction

Many patients with treatment-resistant depression (TRD) require multiple interventions to achieve symptom relief. We explored outcomes from a stepwise, real-world protocol combining transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and intravenous ketamine.

Methods

Twenty-eight adults with major depressive disorder were initially treated with a 50-session spaced tDCS protocol. Non-responders were sequentially offered rTMS (30 sessions of iTBS), followed by intravenous racemic ketamine (6 infusions) if needed. Response was defined as ≥50 % reduction in MADRS scores.

Results

Following tDCS, 46.4 % (13/28) of patients achieved response and 32.1 % achieved remission. Of 11 patients who proceeded to rTMS, 36.4 % (4/11) responded. Among the four who received ketamine, 50 % (2/4) responded. The cumulative response and remission rates were 67.9 % and 53.6 %, respectively. Exploratory analyses revealed no significant baseline differences between responders and non-responders.

Conclusions

This case series suggests that a sequential neuromodulation strategy may increase overall response rates in TRD by capturing different responder profiles across modalities. These findings support the feasibility of a pragmatic stepwise approach and highlight the need for controlled studies to guide personalized sequencing strategies.