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

Article · Chiarenza C, Cavendish BA, Mao D, Zhang Y, La Monica K, Wu GR, De Witte S, Horczak P, Geleyn C, Signorelli MS, Concerto C, Razza LB, Baeken C

- Archive id: doi:10.1016/j.jad.2026.122406
- Published: 2026-08-21
- Venue: Journal of affective disorders
- DOI: https://doi.org/10.1016/j.jad.2026.122406
- PMID: 42628579
- Citations: 0
- Source URL: https://doi.org/10.1016/j.jad.2026.122406
- Provenance: europepmc

## 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.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Novel Psychiatric Therapeutics](https://space-kitty.com/topics/psychiatric-therapeutics)

Cited in dossiers:
- [Novel Psychiatric Therapeutics: State of the Field (October 2026)](https://space-kitty.com/dossiers/psychiatric-therapeutics)

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