Clinical Efficacy and Psychological Mechanisms of an App-Based Digital Therapeutic for Generalized Anxiety Disorder: Randomized Controlled Trial

Abstract

Background Current treatments for generalized anxiety disorder (GAD) often yield suboptimal outcomes, partly because of insufficient targeting of underlying psychological mechanisms (eg, avoidance reinforcement learning). Mindfulness training (MT) has shown efficacy for anxiety; yet, widespread adoption has been limited, partly because of the difficulty in scaling in-person–based delivery. Digital therapeutics are emerging as potentially viable treatments; however, very few have been empirically validated. Objective The aim of this study is to test the efficacy and mechanism of an app-delivered MT that was designed to target a potential mechanism of anxiety (reinforcement learning), based on which previous studies have shown concern regarding feedback and the perpetuation of anxiety through negative reinforcement. Methods Individuals with GAD were recruited using social media advertisements and randomized during an in-person visit to receive treatment as usual (n=33) or treatment as usual+app−delivered MT (Unwinding Anxiety; n=32). The latter was composed of 30 modules to be completed over a 2-month period. Associated changes in outcomes were assessed using self-report questionnaires 1 and 2 months after treatment initiation. Results We randomized 65 participants in this study, and a modified intent-to-treat approach was used for analysis. The median number of modules completed by the MT group was 25.5 (IQR 17) out of 30; 46% (13/28) of the participants completed the program. In addition, the MT group demonstrated a significant reduction in anxiety (GAD-7) compared with the control group at 2 months (67% vs 14%; median change in GAD-7: –8.5 [IQR 6.5] vs –1.0 [IQR 5.0]; P<.001; 95% CI 6-10). Increases in mindfulness at 1 month (nonreactivity subscale) mediated decreases in worry at 2 months (Penn State Worry Questionnaire; P=.02) and decreases in worry at 1 month mediated reductions in anxiety at 2 months (P=.03). Conclusions To our knowledge, this is the first report on the efficacy and mechanism of an app-delivered MT for GAD. These findings demonstrate the clinical efficacy of MT as a digital therapeutic for individuals with anxiety (number needed to treat=1.6). These results also link recent advances in our mechanistic understanding of anxiety with treatment development, showing that app-delivered MT targets key reinforcement learning pathways, resulting in tangible, clinically meaningful reductions in worry and anxiety. Evidence-based, mechanistically targeted digital therapeutics have the potential to improve health at a population level at a low cost. Trial Registration ClinicalTrials.gov NCT03683472; https://clinicaltrials.gov/ct2/show/NCT03683472

Analyzing the Impact of Mobile App Engagement on Mental Health Outcomes: Secondary Analysis of the Unwinding Anxiety Program

“…This study is a secondary data analysis of a previously described stage 1 parallel-group RCT [ 32 ]. As this secondary analysis is interested in system use data and their association with study outcomes, data were taken from the intervention arm only, and study procedures relevant to analyzing the intervention group are summarized in the following sections [ 32 ]. Roy et al [ 32 ] provide detailed information on the study design, procedures, and the results of the randomized trial.…”

“…The data used for these analyses were from the baseline and 2-month time points for the intervention group only [32]. The inclusion criteria were as follows: (1) score ≥10 on the Generalized Anxiety Disorder 7-item scale (GAD-7), (2) owning a smartphone, (3) willingness to receive check-in calls, and (4) aged ≥18 years [32]. Participants were excluded from the study if they reported (1) dose changes of any psychoactive medication in the previous 2 months; (2) needed use of benzodiazepines and hypnotic sleep aids; (3) a history or current diagnosis of bipolar, schizophrenia or schizoaffective, or another psychotic disorder; (4) a significant medical condition that would affect the ability to complete study tasks; (5) cohabitation with someone already enrolled in the study; and (6) having a previous history of using other related apps, specifically Eat Right Now or Craving to Quit, which use similar reinforcement processes to UA [33][34][35].…”

“…Applying this model of engagement, we conducted a secondary analysis using multivariate regression models to examine the associations between in-app engagement (ie, microengagement) and mental health outcomes (ie, macroengagement) for participants with generalized AD (GAD) using a targeted mobile app called Unwinding Anxiety (UA) [ 32 ]. Data were collected from the intervention group in a recently published randomized controlled trial (RCT) that tested UA versus treatment as usual [ 32 ]. The UA app is a theory-driven, multifaceted app that comprises both guided (ie, educational modules) and unguided features (eg, meditations and ecological check-ins) targeting novel reinforcement learning constructs [ 32 , 33 ].…”

“…Data were collected from the intervention group in a recently published randomized controlled trial (RCT) that tested UA versus treatment as usual [ 32 ]. The UA app is a theory-driven, multifaceted app that comprises both guided (ie, educational modules) and unguided features (eg, meditations and ecological check-ins) targeting novel reinforcement learning constructs [ 32 , 33 ]. The results from the primary RCT (N=65) were promising, with participants in the UA group reporting a median reduction in anxiety scores of 8.5 (IQR 6.5; P <.001) and the treatment as usual group reporting a median reduction of 1 (IQR 5; P =.01), representing a 67% versus 14% reduction at the 2-month follow-up [ 32 ].…”

Stepping Out of the Palace of Luxury: Mindfulness and Modern Psychiatry

“…Emerging data suggest that mindfulness training apps may be effective across a range of psychiatric illnesses, including generalized anxiety disorder and nicotine use disorder. And, at least in nicotine use disorder, the mechanism seems to be exactly what we already knew: changes in functioning of the DMN (7,8).…”