This treatment reaches a deep depression circuit that TMS only approaches indirectly
STUDY: Wang M et al, Cell Reports Medicine 2026
STUDY TYPE: Randomized, double-blind, sham-controlled trial
FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, and other Chinese government and institutional grants
Background
Deep in the brain lies an area that regulates mood and emotion, the subgenual anterior cingulate cortex (sgACC). Activating this area can treat depression, but past techniques have required surgery, such as deep brain stimulation. Transcranial magnetic stimulation (TMS) affects this region indirectly, and today’s trial tested a new treatment that reaches it directly without surgery.
Transcranial temporal interference stimulation (tTIS) sends two high-frequency currents through the scalp that interfere to form a low-frequency signal deep in the brain, reaching the sgACC without surgery.
The Study
- 96 adults with moderate-to-severe major depressive disorder, randomized to 2 mA low-current tTIS, 15 mA high-current tTIS, or sham aimed at the left sgACC.
- 10 sessions over two weeks, analyzed by intention to treat.
- Primary outcome: Depression (HDRS-17), up to 3 month follow up.
Results
High-current tTIS beat sham on depression scores at every follow-up. Low-current also beat sham post-treatment and at 1 month, but that edge faded by 3 months. Responses followed the same pattern. 61% with high-current; 28% with low-current; 9% with sham, with benefits fading after three months for all but the high-current group.
Sleep (PSQI) and fatigue improved in both active groups versus sham; anxiety scores didn’t differ between groups.
The 60% response rate is similar to the average response with deep brain stimulation, though difficult to compare across studies.
Side Effects
tTIS was well tolerated, with higher complaints of tingling sensations. The blind was successful; participants couldn’t reliably guess their group.
Limitations
A 2-week course may underestimate tTIS’s full effect.
Practice Implications
- This is groundbreaking research, but the treatment is investigational. Something to watch for in the future.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
