Frequently Asked Questions

High-frequency 10-Hz repetitive transcranial magnetic stimulation was associated with high remission and response rates in this open-label pilot study of bipolar depression. Among 31 participants with bipolar I or bipolar II depression, remission and response rates based on MADRS were 74.2% and 87.1%, respectively. Depression ratings also improved significantly from pretreatment to posttreatment on MADRS, HDRS, CGI-S, and QIDS, all with P < .001.

No treatment-emergent mania or hypomania was observed during the protocol. None of the patients had an increase in YMRS scores suggesting a switch into mania, and YMRS scores improved as treatment continued. The study required participants to be on a suitable mood stabilizer and/or antipsychotic medication before starting rTMS.

The largest reductions toward response and remission occurred after about 4 weeks from baseline. The authors also noted that their data suggest remission may occur before week 5 in bipolar depression, whereas remission with rTMS for treatment-resistant unipolar depression typically requires 6 to 7 weeks.

The study used a standard unipolar depression rTMS protocol applied to bipolar depression: left dorsolateral prefrontal cortex stimulation at 120% of resting motor threshold, 10 Hz for 4-second trains with 26-second intertrain intervals, 3,000 pulses per session. Sessions lasted 37.5 minutes and were given 5 times per week for up to 35 treatments or until remission criteria were met.

The trial enrolled adults aged 18 years or older with DSM-5 bipolar disorder type I or II who were in a current depressive episode lasting at least 4 weeks but less than 3 years. Participants needed a MADRS score of at least 20, YMRS score below 12, and CGI-Severity score of at least 4 at screening. All patients also had to be taking a suitable mood stabilizer and/or antipsychotic medication for at least 4 days before starting rTMS.

Twenty-nine of 31 patients completed treatment. One patient dropped out after feeling uncomfortably stimulated, without being manic or mixed, and one patient stopped because continuing daily treatments was not feasible. The article notes that the dropout rate due to adverse events was 1 in 31 patients, roughly 3%.

Yes, concurrent lamotrigine and lithium were associated with different MADRS trajectories over treatment. Lamotrigine use was associated with lower MADRS scores in both univariate and post hoc multivariate models (-3.84 ± 1.26, P = .01; -2.59 ± 1.27, P = .05), while lithium use was associated with higher MADRS scores (4.05 ± 1.27, P = .003; 3.46 ± 1.34, P = .02). The authors considered these findings novel but stated it is premature to make treatment recommendations from them because this was not a primary aim of the study.

Bipolar II diagnosis was associated with a favorable rTMS effect on univariate analysis (2.76 ± 1.30, P = .04), but this did not remain significant in multivariate testing (1.34 ± 1.35, P = .33). The authors also noted on subanalysis that bipolar I appeared to improve clinically about 5 treatment sessions earlier than bipolar II, although this was not statistically significant.

Yes. Suicidal ideation, measured secondarily with the Columbia Suicide Severity Rating Scale, decreased from 3.74 at screening to 0.75 at treatment culmination. The authors described this as encouraging, while noting that suicidality was not a primary outcome of the study.

The main limitations are that it was a small, open-label pilot study without a control group, which limits causal interpretation. The sample size also limited subgroup analyses, and the observed differences related to concurrent lamotrigine and lithium were not readily explainable. The authors concluded that the findings should be tested in a fully powered, blinded, sham-controlled randomized clinical trial.