Novel 4-Minute Bilateral TBS Noninferior to rTMS for Depression in Older Adults

Bilateral theta burst stimulation (TBS) was noninferior to standard bilateral repetitive transcranial magnetic stimulation (rTMS) for reducing depressive symptoms in older adults with treatment-resistant depression, according to trial results published online ahead of print in JAMA Psychiatry.

“Bilateral rTMS of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in treatment-resistant depression,” researchers explained in the study background. “TBS, a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes.”

The noninferiority trial included 172 older adults with treatment-resistant depression who were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada. Although technicians and participants were aware of the treatment assignment because of the different session lengths, outcome raters were blinded to each patient’s assignment.

Among 85 patients who received rTMS and 79 who received TBS for at least 4 weeks, mean Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 to 17.3 with rTMS and from 25.7 to 15.8 with TBS, according to the study. The 1.55 adjusted difference in improvement favored TBS.

TBS further demonstrated noninferiority on all secondary outcome measures — the 17-item Hamilton Rating Scale for Depression; 16-item Quick Inventory of Depressive Symptomatology, Self-Rated; and Brief Symptom Inventory, Anxiety Subscale — through 12 weeks after treatment, researchers reported. Cognitive outcomes, adverse effects, and all-cause dropout rates were relatively similar between groups.

“Pain ratings were significantly higher with TBS, particularly with right-sided continuous TBS where stimulation was delivered in a 40-second continuous train. However, this did not lead to a higher dropout rate,” researchers wrote. “Taken together, these findings suggest that 4-minute sequential bilateral TBS is comparable with standard 47.5-minute bilateral rTMS in older adults with treatment-resistant depression.”

—Jolynn Tumolo



Blumberger DM, Mulsant BH, Thorpe KE, et al. Effectiveness of standard sequential bilateral repetitive transcranial magnetic stimulation vs bilateral theta burst stimulation in older adults with depression: the FOUR-D randomized noninferiority clinical trial. JAMA Psychiatry. Published online September 21, 2022. doi: 10.1001/jamapsychiatry.2022.2862