Post-traumatic stress disorder (PTSD) significantly impacts individuals, causing various distressing symptoms and functional impairments. While evidence-based therapies exist, not all individuals benefit, and engagement rates are often low. This research aims to address the gap in understanding what facilitates or hinders treatment progress by examining a novel intervention: multi-modular motion-assisted memory desensitization and reconsolidation therapy (3MDR). 3MDR is an immersive virtual reality therapy that involves walking on a treadmill while interacting with personally selected images associated with traumatic memories. This approach emphasizes engagement, recollection, and reprocessing of traumatic experiences, integrating multi-sensory stimuli and dual-attention tasks to promote cognitive and emotional change. However, the interaction of personal characteristics, intervention components, and the treatment context remains unclear. This study utilizes a mixed-methods approach to investigate these complex interrelationships within the framework of 3MDR as a complex intervention, aiming to identify factors associated with varied treatment outcomes.

Existing literature highlights the limitations of current PTSD treatments, with many individuals failing to achieve sufficient symptom relief or dropping out of therapy. Several systematic reviews emphasize the need for research into the factors influencing treatment success, highlighting the lack of understanding regarding the mechanisms of action and the individual variations in response to therapy. There is a growing recognition that psychological therapies should be viewed as complex interventions, acknowledging the intricate interplay between the therapy itself, the therapist, and the patient's broader environment. This necessitates a shift away from simplistic, mechanistic models toward a more nuanced understanding of the multifaceted factors influencing treatment outcomes. The rise of immersive therapies, including virtual reality interventions for various mental health conditions, presents a promising avenue for innovation. 3MDR, with its theoretical grounding in memory reconsolidation and engagement through movement, represents a significant advance in this area, yet requires detailed examination of its components and their interactions to optimize effectiveness.

This study employed a convergent mixed methods design, analyzing quantitative and qualitative data from 10 military veterans participating in a larger randomized controlled trial of 3MDR. Quantitative data included researcher-assessed and self-report clinical measures (CAPS-5, LEC-5, PHQ-9, GAD-7, MSPSS, WSAS, EQ-5D-5L), physiological recordings (heart rate, breathing rate, walking pace), and subjective unit of distress (SUD) scores. Qualitative data were derived from semi-structured interviews exploring participants' experiences, motivations, and reflections on the therapy. Data were analyzed using a person, intervention, and context model. Initial separate analyses of each data type were followed by a comparative analysis, grouping participants into outcome typologies (dramatic, moderate, minimal improvement) based on their CAPS-5 scores. Finally, an interpretative exploration identified patterns and relationships within and between domains for each typology.

Three distinct outcome typologies were identified based on changes in CAPS-5 scores: dramatic improvement (significant reduction in PTSD symptoms), moderate improvement (some reduction), and minimal improvement (little to no change). Analysis across these typologies revealed patterns within three domains: **Person Domain:** Dramatic improvers exhibited better baseline mobility, higher commitment to completing therapy, and greater reductions in subjective distress. No clear differences were found in sociodemographic factors, trauma type, or co-occurring mental health conditions. **Intervention Domain:** All participants found image selection challenging. However, dramatic improvers were more successful in finding highly evocative images and adjusting their selections throughout therapy, maintaining engagement. Moderate improvers experienced difficulties maintaining image impact, while minimal improvers struggled with image selection and sequencing. Therapeutic alliance emerged as crucial, with trust in the therapist significantly impacting treatment success, and a flexible approach to the number of sessions, tailored to the individual needs seemed beneficial. **Context Domain:** Strong initial reactions to the clinic environment were common among dramatic improvers and some moderate improvers but less so in the minimal improvers. No consistent patterns were observed regarding social support, employment status, or the ability to travel to the clinic. Secondary outcome measures (depression, anxiety, social support, work/social adjustment, quality of life) generally reflected the primary outcome patterns, with dramatic improvers showing significant improvement, moderate improvers demonstrating mixed results, and minimal improvers exhibiting either no change or worsening in some areas. However, many aspects of the three domains exhibited no distinct patterns across the three response typologies, such as co-existing mental health conditions, trauma type, social support, or initial apprehension towards therapy.

This study contributes to the understanding of 3MDR's effectiveness by identifying factors within the person, intervention, and context domains associated with varying treatment outcomes. The findings highlight the importance of assessing mobility, facilitating effective image selection and utilization, fostering strong therapeutic alliances, and adapting therapy "dosing" (number of sessions) to suit individual needs. The observed challenges in image selection and sequencing suggest the need for additional support and guidance in this aspect of the therapy. The role of the therapeutic relationship underscores the importance of a trusting and collaborative therapeutic environment. These results support the development of more personalized interventions and highlight the limitations of a one-size-fits-all approach to PTSD treatment.

This study provides valuable insights into the factors influencing 3MDR outcomes. While based on a small sample, the findings suggest that optimizing treatment involves addressing mobility limitations, enhancing image selection strategies, building strong therapeutic alliances, and customizing therapy duration. Future research should focus on larger-scale studies incorporating more granular measures of the identified factors to further refine and personalize this promising virtual reality intervention for PTSD. The model presented offers a valuable framework for future studies aiming to deepen our understanding of complex interventions.

The primary limitation of this study is its small sample size (n=10), limiting the generalizability of findings. The reliance on proxy measures for cognitive engagement and therapeutic alliance also necessitates caution in interpretation. The qualitative data analysis focused on a subset of participants, which may not fully capture the experiences of all individuals in the trial. Future research with larger, more diverse samples and direct measures of key factors would strengthen the findings.