Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites.

Background: While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome.
Methods: Thirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3-4 days posttreatment (T1) and 10-11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses.
Results: Although the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients.
Limitations: The modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10-11 days, whereas similar studies usually follow up for at least one month.
Conclusion: More research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.
Competing Interests: Declaration of competing interest MM, VC: received research funding from Johnson & Johnson Belgium, Lundbeck Belgium, Boehringer Ingelheim Belgium and Takeda Pharmaceuticals Japan for research unrelated to the current project. The authors state that the content of this manuscript was not influenced by any of these agencies. AD, KH, DZ, CBa, GDF, CBe, SDW, BS: Declare that they have no conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)