Five-factor personality and antidepressant response to intermittent theta burst stimulation for major depressive disorder

<h2>Abstract</h2><h3>Background</h3> Five-factor personality has been examined in relation to the natural history of depression and its response to treatment. With respect to rTMS, several five-factor personality dimensions have been associated with treatment outcomes, and open-label data suggests that neuroticism decreases with high-frequency stimulation to the left dorsolateral prefrontal cortex (DLPFC). Here, we examine the relationship between five-factor personality dimensions and antidepressant response leveraging a randomized placebo-controlled trial using the partial N-methyl- D-aspartate (NMDA) receptor agonist, D-Cycloserine, to enhance intermittent theta burst stimulation (iTBS). <h3>Methods</h3> In a 4-week double-blind randomized placebo-controlled trial, fifty individuals with major depressive disorder (NCT03937596) received iTBS+Placebo or iTBS+D-Cycloserine (100mg). Participants completed the Big Five Inventory to assess five-factor personality dimensions, and depressive symptoms were assessed using the clinician rated Montgomery-Åsberg Depression Rating Scale at baseline and after the 4-weeks of treatment. <h3>Results</h3> There was no significant association between five-factor personality dimensions and change in depressive symptoms for either treatment group. Although iTBS+D-Cycloserine was associated with significantly greater antidepressant effect than iTBS+Placebo, neuroticism decreased with similar magnitude in each treatment group. Openness to experience and conscientiousness increased following treatment, and did so with similar magnitudes in both treatment groups. <h3>Conclusions</h3> These data suggest that five-factor personality may not predict antidepressant treatment outcomes with iTBS for major depressive disorder, and that decreases in neuroticism that have been reported in open-label TMS studies may reflect non-specific factors of treatment.