A Randomized Controlled Trial for Identifying the Most Suitable Treatment for Depression Based on Patients’ Attachment Orientation

Objective: Many active treatments exist for major depressive disorder (MDD), but little is known about their differential effects for various subpopulations of patients to guide precision medicine. This is the first randomized controlled trial (RCT) designed to identify differential treatment effects based on patients’ attachment orientations. We tested an a priori preregistered hypothesis of the potential moderating effect of patients’ attachment orientation on the outcome of supportive therapy (ST) versus supportive-expressive therapy (SET). Methods: The RCT was conducted between 2015 and 2021. Individuals with MDD were randomly assigned to 16-week ST or SET. The predefined primary outcome measure was the Hamilton Rating Scale for Depression. Hypotheses were formulated and preregistered before data collection. Results: One hundred patients with MDD were enrolled, 57% women, average age 31.2 (SD = 8.25). Data were analyzed using the intention-to-treat approach. Our hypothesis that attachment anxiety is a significant moderator of treatment outcome was supported (B = −0.09, p =.016): Patients with higher levels of attachment anxiety showed greater treatment efficacy following SET than ST. Although the hypothesis regarding a potential moderating effect of avoidant attachment was not supported, sensitivity analyses revealed that individuals with disorganized attachment orientation (higher scores on both anxious and avoidant attachment) benefited more from SET than from ST (B = −0.07, p =.04). Conclusion: The findings support the clinical utility of patients’ attachment orientation in selecting the most suitable treatment for individuals and demonstrate the methodological utility of RCTs predesigned to test theoretically based models of personalized treatment.