Lurasidone response in bipolar type I depression with childhood trauma exposure.

Importance: Childhood Trauma (CT) worse the course of Bipolar Disorder (BD) and negatively impact 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 impact treatment response and remission.

Design: A multisite, observational, prospective, comparative effectiveness study over 8-week period was conducted.

Setting: A multisite in four 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: For the lurasidone arm 41 participants were assigned, and for lurasidone plus lithium were 43 over 8-week period.

Exposure: Childhood trauma exposure was measured with the Childhood Trauma Questionnaire-Short Form (CTQ-SF) (BD-CT, n=40; BD-non-CT, n=44) were includedMain 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 (CGI-BP) depression severity scores and responder rates.

Results: BD with CT exposure demonstrated a smaller mean reduction in MADRS scores compared to those without CT exposure for both treatments (monotherapy: LS -3.4, CI 95% -6.03, -0.76, p = 0.013; combination therapy: LS -3.1, CI 95% -5.36, -0.63, p = 0.014). The presence of CT exposure, particularly physical abuse, 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 childhood trauma (CT), particularly physical abuse, attenuates the antidepressant effects of lurasidone in bipolar disorder (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.