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. What is the public health significance of this article?This study is the first randomized controlled trial (RCT) predesigned to test the differential effect of treatments based on the patients' pretreatment attachment orientations. The findings demonstrate the ability of attachment orientation to serve as an empirically informed tool for a personalized match between individuals and their most effective treatment.

The alliance has been a leading player in the long-running debate on whether therapeutic change is driven by factors common across distinct treatments or by treatment-specific factors. The present study disentangled between-patients differences in alliance strength from within-patient changes to investigate whether two treatments with identical goals but based on different roles of alliance differ in the within-patient effect of alliance on outcome. Both treatments are aimed at improving the patients’ interpersonal abilities, but in the supportive treatment (ST) the alliance is the main specific factor, whereas in the supportive–expressive treatment (SET) it is conceptualized as a common factor. One hundred patients were randomized to receive either ST or SET. Treatment outcome and alliance were assessed weekly. Treatment condition significantly moderated the effect of within-patient changes in the alliance (relative to its mean) on subsequent treatment outcome, so that any increases in state-like alliance predicted lower levels of subsequent depressive symptoms in ST than in SET.

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Supportive-expressive (SE) psychodynamic treatment is based on the identification of and working through the patient’s signature core conflictual relationship theme. According to the SE framework, when termination is anticipated, separation conflict arises, and the actualization of the patient’s interpersonal wish in the relationship with the therapist is no longer possible. The disactualization of the patient’s wish in the relationship with the therapist may cause patients to regress to their maladaptive prototype responses (Nof, Leibovich, & Zilcha-Mano, 2017), which may manifest as a rupture in the therapeutic alliance. The present work integrates constructs based on the SE framework, specifically the disactualization of the patient’s wish at the end of treatment, with the framework of alliance ruptures and their resolution (Safran & Muran, 2000). We propose a conceptual clinical model to guide therapists in the successful resolution of alliance ruptures, which are the result of the disactualization of the patient’s interpersonal wish. We propose a two-stage process to achieve successful resolution of termination ruptures: (a) identification of termination ruptures and (b) addressing and resolving termination ruptures. For each stage, we propose practice-based guidelines and steps to follow. We demonstrate the proposed guidelines based on the case study of a patient with major depressive disorder. We used three sources of information from the case study: verbal transcripts of the therapy sessions, questionnaires, and semistructured posttreatment interviews.