Abstract
Mixed depression is probably different in terms of clinical course and response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is well established in non-mixed depression, and theta-burst stimulation (TBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, TBS has not been adequately studied in mixed states. This study was a double-blind, six-week, sham-controlled, and randomized clinical trial of bilateral TBS targeting the right and left dorsolateral prefrontal cortex, respectively. Adults with bipolar and major depressive disorder experiencing an acute mixed depression were eligible if they had not benefited from a first- or second-line treatment for acute unipolar or bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments. Out of 100 patients included, 90 composed modified intention-to-treat sample, which was patients that completed at least one week of the intervention. There were no significant differences in Montgomery-Asberg depression rating scale score changes (least squares mean difference between groups at week 3, −0.06 [95% CI, − 3.39 to 3.51; P = 0.97] in favor of sham TBS). Response and remission rates per MADRS were also not statistically different among active and sham groups (35.7% vs. 43.7%, and 28.5% vs. 37.5% respectively at week 6, ps > 0.51). No other analyses from baseline to weeks 3 or 6 revealed significant time x group interaction or mean differences among groups in the mITT sample. Bilateral TBS targeting the DLPFC is not efficacious as an add-on treatment of acute bipolar and unipolar mixed depression. ClinicalTrials.govIdentifier: NCT04123301
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Conceived and designed the clinical trial: DFT, ARB, RAM. Contributed to the acquisition, analysis, or interpretation of data for the work: DFT, PS, CGRS, DHM, LCLV, IK, LB, PMF, ARB, RAM. Wrote the first draft of the manuscript: DFT. Contributed to the writing of the manuscript: ARB, RAM.
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DFT worked as a speaker and produced scientific source during the last two years for the following pharmaceutical companies: Cristália, Aché, Torrent, Abbott, Lundbeck. ARB reports grants from SaoPaulo Research State Foundation (FAPESP, 2017/50223-6, 2018/10861-7, 2019/06009-6), Newton Advanced Fellowship (12/1010), Brazilian National Council of Scientific Development Productivity Support (PQ-1B) and University of Sao Paulo Medical School Productivity Support (PIPA-A). . RAM reports grants from Sao Paulo Research State Foundation (FAPESP) and from the National Research Council (CNPq). Other authors declare no conflicts of interest.
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Tavares, D.F., Suen, P., Rodrigues dos Santos, C.G. et al. Treatment of mixed depression with theta-burst stimulation (TBS): results from a double-blind, randomized, sham-controlled clinical trial. Neuropsychopharmacol. 46, 2257–2265 (2021). https://doi.org/10.1038/s41386-021-01080-9
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DOI: https://doi.org/10.1038/s41386-021-01080-9
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