A Pilot Study of High-Frequency Transcranial Magnetic Stimulation for Bipolar Depression

Objective: Repetitive transcranial magnetic stimulation (rTMS) is a standard treatment approach for major depressive disorder. There is growing clinical experience to support the use of high-frequency left-sided rTMS in bipolar depression. This study collected open-label safety and effectiveness data in a sample of patients with bipolar depression.

Methods: Thirty-one adults (13 male/ 18 female; mean age: 42.2 [14.3] years) with bipolar (I or II) depression verified by DSM-5 criteria were recruited at Sheppard Pratt and Mayo Clinic between August 2017 and February 2020 for rTMS. Standardized treatment protocols employed 6 weeks of 10-Hz rTMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4-second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥50% or score <10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.

Results: The majority of patients with bipolar depression reached response (n = 27; 87.1%) and remission (n = 23; 74.2%). Older age and concurrent treatment with lithium were associated with higher MADRS scores throughout the treatment course (0.1 ± 0.05, P =.05; 4.05 ± 1.27, P = .003, respectively). Concurrent treatment with lamotrigine was associated with lower MADRS scores (-3.48 ± 1.26, P = .01). Treatment with rTMS was safe and well tolerated. There were no completed suicides, induced manic episodes, or other serious adverse events.

Conclusion: Although preliminary, the present findings are encouraging regarding the safety and effectiveness of 10-Hz rTMS for bipolar depression.

Trial Registration: ClinicalTrials.gov identifier: NCT02640950.