Efficacy of a Smartphone-Based Digital Therapeutic (Anzeilax) in Generalized Anxiety Disorder: Randomized Controlled Trial.

BACKGROUND: Individuals with generalized anxiety disorder (GAD) often face challenges with self-regulation and limited access to traditional therapy. Although acceptance and commitment therapy (ACT) has demonstrated both efficacy and effectiveness in promoting psychological flexibility, scalable solutions are necessary to address these barriers. This study introduces Anzeilax, an ACT-based digital therapeutic (DTx) that incorporates self-talk as a novel mechanism of action (MoA) to enhance psychological flexibility in the treatment of GAD. OBJECTIVE: This study aimed to evaluate the efficacy of Anzeilax in reducing anxiety symptoms in individuals with GAD. METHODS: A 10-week, parallel-group, superiority randomized controlled trial (RCT) was conducted with 96 participants diagnosed with GAD (Generalized Anxiety Disorder 7-item scale [GAD-7] scores≥10, age≥19 years). The participants were randomly assigned (1:1) to receive either Anzeilax alongside treatment as usual (TAU, treatment group; n=48, 50%) or TAU alone (control group; n=48). Only the outcome evaluators were blinded to the group assignment. The primary outcome was the change in the GAD-7 score from baseline to week 10. The secondary outcomes included the Beck Anxiety Inventory (BAI) for anxiety symptoms, the Penn State Worry Questionnaire (PSWQ) for pathological worry, and the Hospital Anxiety and Depression Scale (HADS) for anxiety (HADS-A) and depression (HADS-D) symptoms. All self-report outcomes were assessed at baseline and at weeks 5 (midintervention), 10 (postintervention), and 15 (follow-up). RESULTS: During the trial, 34 (71%) and 31 (65%) participants in the treatment group maintained at least 80% of the prescribed usage frequency at weeks 5 and 10, respectively. Based on the full analysis set (FAS), participants using Anzeilax demonstrated significant improvement in anxiety symptoms compared to the control group. Analysis of the primary outcome at 10 weeks postintervention compared to baseline exhibited a significant reduction in GAD-7 scores (adjusted mean difference -2.26, 95% CI -3.78 to -0.74, P=.002). Secondary outcomes at the same time point indicated consistent improvements, with significant group-by-time interactions observed in the GAD-7 (Cohen d=0.60, P=.008), BAI (Cohen d=0.50, P=.008), PSWQ (Cohen d=0.62, P=.002), and HADS-A (Cohen d=0.50, P=.01) scores. These improvements were sustained at the follow-up assessment (week 15). Although the differences in depressive symptoms between the two groups did not present statistical significance, notable improvements were observed in the treatment group. CONCLUSIONS: Anzeilax demonstrated clinically meaningful efficacy in reducing anxiety symptoms when combined with TAU. The results showed consistent improvements across multiple anxiety measures, with effects sustained through follow-up. The incorporation of context-sensitive self-talk within an ACT-based DTx framework offers a promising and accessible solution for treating individuals with GAD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06010654; https://clinicaltrials.gov/study/NCT06010654.