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Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

Cecilia Chiarenza·Beatriz Araújo Cavendish·Deng Mao·Yichen Zhang·Kevin La Monica·Guo-Rong Wu·Sara De Witte·Paula Horczak·Cisse Geleyn·Maria Salvina Signorelli·Carmen Concerto·Laís Boralli Razza·Chris Baeken
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Abstract

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

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HumansFemaleMaleAdultMajor Depressive DisorderExploratory BehaviorTemperamentDepressive Disorder, Treatment-ResistantTranscranial Magnetic StimulationMiddle AgedTreatment OutcomeDorsolateral Prefrontal CortexPersonality InventoryPsychiatric Status Rating ScalesCharacterAccelerated iTBSFast responseNovelty seekingTCITreatment-resistant depressionJournal ArticleRandomized Controlled Trial

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Cecilia Chiarenza, Beatriz Araújo Cavendish, Deng Mao, Yichen Zhang, Kevin La Monica, Guo-Rong Wu, Sara De Witte, Paula Horczak, Cisse Geleyn, Maria Salvina Signorelli, Carmen Concerto, Laís Boralli Razza, Chris Baeken. 2026-08-21. Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.. https://doi.org/10.1016/j.jad.2026.122406

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Journal Article; Randomized Controlled Trial resourceAccelerated iTBS subjectAdult subjectCharacter subjectDepressive Disorder, Treatment-Resistant subjectDorsolateral Prefrontal Cortex subjectExploratory Behavior subjectFast response subjectFemale subjectHumans subjectJournal Article subjectMajor Depressive Disorder subjectMale subjectMiddle Aged subjectNovelty seeking subjectPersonality Inventory subject

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