Abstract

Importance

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD).

Objective

To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD.

Design, Setting, and Participants

This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo University, Lishui Second People’s Hospital, and Taizhou Second People’s Hospital). Adult patients (aged 18-65 years) who were diagnosed with major depressive disorder were recruited. Participants were randomly assigned to 1 of 4 interventions: active tDCS + active rTMS, sham tDCS + active rTMS, active tDCS + sham rTMS, and sham tDCS + sham rTMS. Data analysis followed an intention-to-treat approach.

Intervention

Patients received a 2-week course of treatment. The tDCS was administered using a 2-mA direct current stimulator with electrodes placed on the left and right dorsolateral prefrontal cortex (DLPFC). Each tDCS session lasted 20 minutes and was conducted 30 to 60 minutes prior to the rTMS session for a total of 10 sessions. The rTMS was delivered at a frequency of 10 Hz using a figure-8 coil placed on the left DLPFC, with each session consisting of 1600 pulses. Treatments were administered 5 times per week for 2 weeks. Sham treatments were performed with a pseudostimulation coil and emitted only sound.

Main Outcomes and Measures

The primary outcome was the change in total score from baseline to week 2 on the 24-item Hamilton Depression Rating Scale (HDRS-24; score range: 0-52, with the highest score indicating more severe symptoms).

Results

A total of 240 participants (139 females [57.9%]; mean [SD] age, 32.50 [15.18] years) were included. As a primary outcome, patients who received active tDCS + active rTMS showed a significantly greater reduction in mean (SD) HDRS-24 total scores compared with patients in the other 3 groups (active tDCS + active rTMS: 18.33 [5.39], sham tDCS + active rTMS: 14.86 [5.59], active tDCS + sham rTMS: 9.21 [4.61], and sham tDCS + sham rTMS: 10.77 [5.67]; F3,236 = 35.79; η2 = 0.31 [95% CI, 0.21-0.39]; P < .001).

Conclusions and Relevance

This trial found that tDCS + rTMS was a more effective and safe treatment option than either the tDCS or rTMS intervention alone for patients with MDD.

Trial Registration

China Clinical Trial Registry Identifier ChiCTR2100052122.

Key Points

Question Does the combination of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) vs each treatment alone provide better outcomes in the treatment of depression?

Findings In this randomized clinical trial involving 240 participants, those who received active tDCS + active rTMS had a greater reduction in the 24-item Hamilton Depression Rating Scale total score than those who received sham tDCS + active rTMS, active tDCS + sham rTMS, or sham tDCS + sham rTMS after 2 weeks of treatment.

Meaning  The findings indicate that tDCS + rTMS is more effective than either tDCS or rTMS alone in depression treatment and has a comparable safety profile.

요약

소개

반복적 경두개 자기 자극(repetitive transcranial magnetic stimulation, rTMS)과 경두개 직류 자극(transcranial direct current stimulation, tDCS)은 각각 우울증 치료에 효과적인 것으로 인정받고 있다. 그러나 rTMS와 tDCS를 결합했을 때 주요 우울 장애(MDD) 치료에서 더 나은 효능이 있는지 여부는 아직 알려져 있지 않다. 본 연구는 MDD 환자에서의 rTMS, tDCS, tDCS+rTMS, 그리고 가짜tDCS+가짜rTMS 치료의 임상 효과와 안전성을 비교하는 것을 목적으로 한다.

결과

240명의 참가자가 포함된 이 무작위 임상 시험에서, 활성 tDCS + 활성 rTMS를 받은 환자들이 2주 치료 후, 가짜 tDCS + 활성 rTMS, 활성 tDCS + 가짜 rTMS, 또는 가짜 tDCS + 가짜 rTMS를 받은 환자들보다 24항목 해밀턴 우울 평가 척도(24-item Hamilton Depression Rating Scale (HDRS-24)) 총점에서 더 큰 감소를 보였다.

결론 및 의의

주요우울장애에서 tDCS와 rTMS의 병합 치료가 tDCS 또는 rTMS 단독 치료보다 더 효과적이며, 안전성 프로필은 두 치료가 유사하다.