Bilateral Theta Burst Stimulation Effective in Treatment-Resistant Depression

Utilization of theta burst stimulation instead of repetitive transcranial magnetic stimulation could increase treatment access for older adults with treatment-resistant depression.

Bilateral theta burst stimulation (TBS) is superior to bilateral repetitive transcranial magnetic stimulation (rTMS) for patients with treatment-resistant depression (TRD), according to study findings published in JAMA Psychiatry.

Patients (N=172) with TRD were recruited from the Center for Addiction and Mental Health in Canada between 2016 and 2020. Patients were randomly assigned in a 1:1 ratio to receive either 4 to 6 weeks of TBS (n=85; 52.9% women; mean age, 66.3 [SD, 5.3] years) or rTMS (n=87; 54.0% years; mean age, 67.1 [SD, 6.7 years]). Change in Montgomery-Åsberg Depression Rating Scale (MADRS) up to 12-weeks posttreatment was evaluated. Treatment response was defined as a score improvement of at least 50% from baseline. Remission was defined as MADRS score of 10 or less, 17-item Hamilton Rating Scale for depression (HRDS-17) score of 7 or less, and 16-item Quick Inventory of Depressive Symptomology (QIDS-SR-16) score of 5 or less.

The TBS and rTMS cohorts, MADRS scores were 26 (SD, 4.9) and 25.7 (SD, 4.5) points, and their depressive episode had lasted for 71.5 (SD, 109.8) and 50.2 (SD, 82.3) months, respectively. Additionally, 14.1% and 17.2% experienced 4 or more failed treatments, 9.4% and 16.1% had a history of electroconvulsive therapy, and 14.1% and 17.2% had previously underwent rTMS, respectively.

The MADRS scores at the final follow-up differed by 1.547 points between cohorts (90% CI, -0.66 to 3.75; P <.001) and favored TBS. In total, 44.3% of TBS and 32.9% of rTMS recipients were responders (P <.001) and 35.4% and 32.9% met the criteria for remission (P =.046), respectively. In the sensitivity analysis, the difference was 1.22 points favoring TBS.

Since bilateral TBS takes four minutes to deliver, the use of TBS instead of standard rTMS (which takes 47.5 minutes to deliver) could increase the capacity of brain simulation programs that serve older adults.

The final HRSD-17 scores differed by 0.917 points and favored TBS (90% CI, -0.72 to 2.56; P <.001) with 41.9% of the TBS cohort and 29.6% of the rTMS cohort responding (P <.001), and 33.8% and 27.2% meeting the criteria for remission (P =.01), respectively. Similar findings for QIDS-16 were observed, in which the final score differed by 1.268 points favoring TBS (90% CI, -0.1 to 2.67; P <.001), and more TBS recipients responded (44.3% vs 35.7%; P =.001) and achieved remission (31.6% vs 21.4%; P =.002) compared with rTMS, respectively.

The most common adverse events reported by the TBS and rTMS cohorts were headache (54.1% vs 56.3%), dizziness (21.2% vs 19.5%), back or neck pain (10.6% vs 6.9%), anxiety or agitation (9.4% vs 8.0%), nausea (8.2% vs 6.9%), and fatigue (5.9% vs 5.7%), respectively.

This study was limited by recruitment interruption due to the COVID-19 pandemic.

Study authors concluded, “We showed that bilateral TBS was noninferior to standard bilateral rTMS in improving depression, and similarly well-tolerated, in a real-world sample of older adults with TRD. Since bilateral TBS takes 4 minutes to deliver, the use of TBS instead of standard rTMS (which takes 47.5 minutes to deliver) could increase the capacity of brain simulation programs that serve older adults.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Blumberger DM, Mulsant BH, Thrope 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. 2022;e222862. doi:10.1001/jamapsychiatry.2022.2862