Clinical Summary: A Pilot Study of High-Frequency Transcranial Magnetic Stimulation for Bipolar Depression
Bipolar depression remains difficult to treat, with few approved options and ongoing concern about treatment-emergent affective switching with antidepressants. This study addresses whether a standard high-frequency repetitive transcranial magnetic stimulation protocol can reduce depressive symptoms in bipolar I and bipolar II depression without provoking mania or hypomania.
Key Findings
- Remission and response rates based on MADRS score were 74.2% and 87.1%, respectively, across the entire cohort.
- Of the 31 patients who began treatment, 29 completed treatment; 1 patient dropped out due to feeling uncomfortably stimulated, and 1 due to not being able to continue with daily treatments.
- Depression ratings improved from pretreatment to posttreatment on MADRS, HDRS, CGI-S, and QIDS, all P < .001.
- Concurrent lamotrigine 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, respectively), while concurrent lithium was associated with higher MADRS scores (4.05 ± 1.27, P = .003; 3.46 ± 1.34, P = .02, respectively).
- Suicidal ideation decreased on the C-SSRS from 3.74 to 0.75 from screening to treatment culmination, and none of the patients had any increase in YMRS scores to suggest switch into mania, and the scores improved as the treatments continued.
High-frequency 10-Hz repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex produced high remission and response rates in bipolar depression in this pilot sample, with no treatment-emergent mania or hypomania observed. For patients already maintained on mood-stabilizing treatment, this protocol appears clinically promising enough to consider where available while awaiting sham-controlled trials.
Practice Implications
- For bipolar I or bipolar II depression in patients already receiving a suitable mood stabilizer or antipsychotic medication, standard left DLPFC 10-Hz repetitive transcranial magnetic stimulation is a reasonable neuromodulation option to discuss when depressive symptoms remain significant.
- Monitor manic symptoms during treatment with structured assessment such as the YMRS, but this study found no increase in YMRS scores and no switch into mania or hypomania during the protocol.
- Set expectations that the largest reductions toward response and remission occurred after 4 weeks from baseline, which can help guide adherence discussions around daily weekday treatment.
- Review concurrent medications carefully: lamotrigine was associated with lower MADRS scores, whereas lithium was associated with higher MADRS scores over treatment, so medication context should be documented and considered when interpreting response.
