Virtual reality-based Avatar Therapy for treatment-resistant major depressive disorder: A pilot study

• Avatar Therapy for TRD is a VR-based intervention with strong experiential and relational components • Evaluate the efficacy of Avatar Therapy for TRD • Depression, anxiety, self-esteem, quality of life, and functioning improved following Avatar Therapy of TRD • Avatar therapy for TRD demonstrated good acceptability and feasibility • Future studies should assess efficacy in larger controlled samples and its long-term outcomes A bstract Major depressive disorder (MDD) is a common and disabling mental health condition, with a substantial proportion of patients failing to achieve symptom relief through standard pharmacological or psychotherapeutic treatments. Treatment-resistant depression (TRD), therefore, remains a significant clinical and public health challenge. To address this, our team developed Avatar Therapy, a virtual reality–based intervention with strong experiential and relational components. This pilot clinical trial aimed to evaluate the short-term efficacy of Avatar Therapy for TRD on 12 participants. During therapy sessions, participants engaged in dialogue in virtual reality with an avatar representing a person who played a significant role in their depressive symptoms. The avatar was animated in real-time by the therapist. The primary outcomes were the rates of response and remission, along with depressive symptom severity. Secondary outcomes were severity of anxiety symptoms, self-esteem, quality of life, and functioning. Changes in these outcomes between the pre- and post-therapy assessment periods were analyzed using linear mixed-effects models. Among completers, the response rate was 80%, and the remission rate was 20%. At post-therapy, results showed a significant large reduction in depressive symptoms as measured both by self-report (d=1.48, p<0.001) and clinician-rated assessments (d=1.36, p<0.001). Moreover, large significant improvements were observed in the severity of anxiety (d=1.27, p<0.001), self-esteem (d=1.11, p=0.003), quality of life (d=1.42, p<0.001), and functioning (d=1.21, p=0.003). This unique psychotherapy shows promising preliminary results for treating individuals with TRD. Future trials should assess efficacity in larger controlled samples and its long-term out.