Abstract
Auditory hallucination (AH) is a distressing and disabling symptom in patients with schizophrenia spectrum disorder, particularly in those who do not respond to antipsychotics. The aim of this study is to examine the efficacy of AVATAR (Audio Visual Assisted Therapy Aid for Refractory auditory hallucinations) therapy for medication-resistant AH in patients with schizophrenia spectrum disorder. A systematic search was conducted across five major databases for randomized controlled trials (RCTs) investigating AVATAR therapy for patients with medication-resistant AH, with control conditions such as treatment-as-usual (TAU), cognitive behavioral therapy (CBT), or supportive therapy. The primary outcome was AH severity improvement, measured by the Psychotic Symptom Rating Scale-Auditory Hallucination. The secondary outcomes were positive and negative symptoms (assessed using the Positive And Negative Syndrome Scale), quality of life, depression, anxiety, and acceptance (all-cause discontinuation). Additionally, we evaluated the long-term efficacy by examining the sustained effects after treatment discontinuation. Six RCTs (n = 675; 64.7% male; mean age 39.4 [SD 4.8] years) were included. AVATAR therapy was associated with AH improvement (mean difference [MD], -2.97; 95%CI: -4.03, -1.90) and positive symptoms reduction (MD, -1.13; 95%CI: -2.14, -0.11) compared to controls. It also showed efficacy in improving depressive symptoms, anxiety, and quality of life, with small-to-medium effect sizes. The three-month follow-up effects remained consistent with treatment effect at study endpoints across all outcomes. The all-cause discontinuation rate did not differ between AVATAR therapy and controls. Given its potential benefits, clinicians may consider implementing AVATAR therapy for patients with medication-resistant symptoms. However, the development of standardized treatment protocols or manuals is essential to ensure treatment fidelity and guide future clinical and research applications.