Lurasidone response in bipolar type I depression with childhood trauma exposure

Importance: Childhood trauma (CT) worse the course of bipolar disorder (BD) and negatively impacts treatment outcomes. Despite the recognized influence of CT on clinical trajectories, limited evidence exists on how it affects specific pharmacological responses in BD. Objective: This study aimed to investigate the effectiveness of lurasidone in BD type I depression, with a focus on how CT exposure impacts treatment response and remission. Design: A multisite, observational, prospective, comparative effectiveness study over an 8-week period was conducted. Setting: A multisite in 4 clinical research sites in Colombia. Participants: A total of 84 adults with BD type I depression were enrolled (lurasidone=41, lurasidone with lithium=43). Intervention: Over an 8-week period, 41 participants were assigned to the lurasidone arm and 43 to the lurasidone plus lithium arm. Exposure: Childhood trauma exposure was measured with the Childhood Trauma Questionnaire-Short Form. BD with CT (n=40) and BD without CT (n=44) were included. Main outcome and measures: The primary outcome was changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Secondary outcomes included changes in Clinical Global Impression-Bipolar depression severity scores and responder rates. Results: Bipolar disorder with CT exposure demonstrated a smaller mean reduction in MADRS scores compared to those without CT exposure for both treatments (monotherapy: Least Square (LS) -3.4, 95% CI, -6.03 to -0.76, P=.013; combination therapy: LS -3.1, 95% CI, -5.36 to -0.63, P=.014). The presence of CT exposure, particularly physical abuse (PA), was associated with poorer response rates. Notably, lurasidone in combination with lithium showed superior outcomes compared to monotherapy, although effectiveness was attenuated in participants with documented CT exposure. Conclusions: This study provides real-world evidence suggesting that CT exposure may modify treatment response in BD type I depression. Our findings underscore the importance of CT screening to guide personalized treatment strategies. Relevance: This study provides evidence that CT, particularly PA, attenuates the antidepressant effects of lurasidone in BD type I depression, leading to lower response and remission rates in both monotherapy and combination therapy with lithium. These findings underscore the clinical importance of screening for CT in BD to guide personalized treatment strategies. Identifying trauma history may help clinicians optimize treatment selection, considering the potential need for combination pharmacotherapy and adjunctive trauma-focused psychotherapeutic interventions to improve outcomes in this vulnerable population.