Accelerated intermittent theta-burst stimulation Shows Promise in Treatment-Resistant Bipolar Depression: JAMA

In patients with treatment-resistant bipolar disorder, participants who underwent aiTBS treatment showed significantly reduced depression scores post-treatment compared to those who received sham treatment, the researchers reported.

Bipolar disorder (BD) is a chronic and disabling condition primarily characterized by episodes of depression that dominate the course of the illness. Recent studies have shown significant progress in the clinical effectiveness of transcranial magnetic stimulation for treatment-resistant major depressive disorder (MDD) through an accelerated regimen known as intermittent theta-burst stimulation (aiTBS). However, whether this treatment approach is effective for individuals with treatment-refractory BD remains uncertain.

Against the above background, Yvette I. Sheline, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues aimed to evaluate aiTBS effectiveness for treatment-refractory BD.

For this purpose, the researchers conducted a randomized clinical trial from 2022 to 2024, including participants with treatment-resistant BD with moderate to severe depressive episodes referred from the Penn Bipolar outpatient clinic.

The participants in the study had experienced failure with two or more previous antidepressant treatments as per the Antidepressant Treatment History Form criteria, did not have any other primary psychiatric diagnosis, were taking a mood stabilizer for at least four weeks, and had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or above.

The researchers used resting-state functional magnetic resonance imaging before the treatment to compute personalized left dorsolateral prefrontal cortex target by connectivity to the subgenual anterior cingulate cortex. Patients were randomized in a 1:1 ratio to per day ten sessions of imaging-guided active or sham aiTBS for five days with one session per hour at 90% resting motor threshold for 90 000 pulses total.

Patients were randomized 1:1 to 10 daily imaging-guided active or sham aiTBS sessions for five days. The treatment regimen consisted of one session per hour, administered at 90% of the resting motor threshold, totaling 90,000 pulses overall.

The primary outcome was repeated MADRS scores before and after treatment.

The following were the key findings of the study:

• Twenty-four participants (50% female; mean age, 43.3 years) were randomized to active (n = 12) or sham (n = 12) aiTBS.
• All participants completed treatment and 1-month follow-up. MADRS scores were significantly lower in the active group (mean, 30.4 at baseline; 10.5 after treatment) than in the sham group (28.0 at baseline; 25.3 after treatment) at treatment end (estimated difference, –14.75).

The findings showed that aiTBS is more effective than sham stimulation for reducing depressive symptoms in patients with treatment-resistant BD.

"Additional trials are necessary to assess the long-term effectiveness of aiTBS and to compare its efficacy with other treatment options," the research team concluded.

Reference:

Sheline YI, Makhoul W, Batzdorf AS, et al. Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry. Published online July 10, 2024. doi:10.1001/jamapsychiatry.2024.1787