Demographic and clinical characteristics associated with anxiety and depressive symptom outcomes in users of a digital mental health intervention incorporating a relational agent.

BACKGROUND: Digital mental health interventions (DMHIs) may reduce treatment access issues for those experiencing depressive and/or anxiety symptoms. DMHIs that incorporate relational agents may offer unique ways to engage and respond to users and to potentially help reduce provider burden. This study tested Woebot for Mood & Anxiety (W-MA-02), a DMHI that employs Woebot, a relational agent that incorporates elements of several evidence-based psychotherapies, among those with baseline clinical levels of depressive or anxiety symptoms. Changes in self-reported depressive and anxiety symptoms over 8 weeks were measured, along with the association between each of these outcomes and demographic and clinical characteristics. METHODS: This exploratory, single-arm, 8-week study of 256 adults yielded non-mutually exclusive subsamples with either clinical levels of depressive or anxiety symptoms at baseline. Week 8 Patient Health Questionnaire-8 (PHQ-8) changes were measured in the depressive subsample (PHQ-8 ≥ 10). Week 8 Generalized Anxiety Disorder-7 (GAD-7) changes were measured in the anxiety subsample (GAD-7 ≥ 10). Demographic and clinical characteristics were examined in association with symptom changes via bivariate and multiple regression models adjusted for W-MA-02 utilization. Characteristics included age, sex at birth, race/ethnicity, marital status, education, sexual orientation, employment status, health insurance, baseline levels of depressive and anxiety symptoms, and concurrent psychotherapeutic or psychotropic medication treatments during the study. RESULTS: Both the depressive and anxiety subsamples were predominantly female, educated, non-Hispanic white, and averaged 38 and 37 years of age, respectively. The depressive subsample had significant reductions in depressive symptoms at Week 8 (mean change =-7.28, SD = 5.91, Cohen's d = -1.23, p < 0.01); the anxiety subsample had significant reductions in anxiety symptoms at Week 8 (mean change = -7.45, SD = 5.99, Cohen's d = -1.24, p < 0.01). No significant associations were found between sex at birth, age, employment status, educational background and Week 8 symptom changes. Significant associations between depressive and anxiety symptom outcomes and sexual orientation, marital status, concurrent mental health treatment, and baseline symptom severity were found. CONCLUSIONS: The present study suggests early promise for W-MA-02 as an intervention for depression and/or anxiety symptoms. Although exploratory in nature, this study revealed potential user characteristics associated with outcomes that can be investigated in future studies. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov (#NCT05672745) on January 5th, 2023.

User Engagement Clusters of an 8-Week Digital Mental Health Intervention Guided by a Relational Agent (Woebot): Exploratory Study.

BACKGROUND: With the proliferation of digital mental health interventions (DMHIs) guided by relational agents, little is known about the behavioral, cognitive, and affective engagement components associated with symptom improvement over time. Obtaining a better understanding could lend clues about recommended use for particular subgroups of the population, the potency of different intervention components, and the mechanisms underlying the intervention's success. OBJECTIVE: This exploratory study applied clustering techniques to a range of engagement indicators, which were mapped to the intervention's active components and the connect, attend, participate, and enact (CAPE) model, to examine the prevalence and characterization of each identified cluster among users of a relational agent-guided DMHI. METHODS: We invited adults aged 18 years or older who were interested in using digital support to help with mood management or stress reduction through social media to participate in an 8-week DMHI guided by a natural language processing-supported relational agent, Woebot. Users completed assessments of affective and cognitive engagement, working alliance as measured by goal and task working alliance subscale scores, and enactment (ie, application of therapeutic recommendations in real-world settings). The app passively collected data on behavioral engagement (ie, utilization). We applied agglomerative hierarchical clustering analysis to the engagement indicators to identify the number of clusters that provided the best fit to the data collected, characterized the clusters, and then examined associations with baseline demographic and clinical characteristics as well as mental health outcomes at week 8. RESULTS: Exploratory analyses (n=202) supported 3 clusters: (1) "typical utilizers" (n=81, 40%), who had intermediate levels of behavioral engagement; (2) "early utilizers" (n=58, 29%), who had the nominally highest levels of behavioral engagement in week 1; and (3) "efficient engagers" (n=63, 31%), who had significantly higher levels of affective and cognitive engagement but the lowest level of behavioral engagement. With respect to mental health baseline and outcome measures, efficient engagers had significantly higher levels of baseline resilience (P<.001) and greater declines in depressive symptoms (P=.01) and stress (P=.01) from baseline to week 8 compared to typical utilizers. Significant differences across clusters were found by age, gender identity, race and ethnicity, sexual orientation, education, and insurance coverage. The main analytic findings remained robust in sensitivity analyses. CONCLUSIONS: There were 3 distinct engagement clusters found, each with distinct baseline demographic and clinical traits and mental health outcomes. Additional research is needed to inform fine-grained recommendations regarding optimal engagement and to determine the best sequence of particular intervention components with known potency. The findings represent an important first step in disentangling the complex interplay between different affective, cognitive, and behavioral engagement indicators and outcomes associated with use of a DMHI incorporating a natural language processing-supported relational agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT05672745; https://classic.clinicaltrials.gov/ct2/show/NCT05672745.

A Therapeutic Relational Agent for Reducing Problematic Substance Use (Woebot): Development and Usability Study.

BACKGROUND: Misuse of substances is common, can be serious and costly to society, and often goes untreated due to barriers to accessing care. Woebot is a mental health digital solution informed by cognitive behavioral therapy and built upon an artificial intelligence-driven platform to deliver tailored content to users. In a previous 2-week randomized controlled trial, Woebot alleviated depressive symptoms. OBJECTIVE: This study aims to adapt Woebot for the treatment of substance use disorders (W-SUDs) and examine its feasibility, acceptability, and preliminary efficacy. METHODS: American adults (aged 18-65 years) who screened positive for substance misuse without major health contraindications were recruited from online sources and flyers and enrolled between March 27 and May 6, 2020. In a single-group pre/postdesign, all participants received W-SUDs for 8 weeks. W-SUDs provided mood, craving, and pain tracking and modules (psychoeducational lessons and psychotherapeutic tools) using elements of dialectical behavior therapy and motivational interviewing. Paired samples t tests and McNemar nonparametric tests were used to examine within-subject changes from pre- to posttreatment on measures of substance use, confidence, cravings, mood, and pain. RESULTS: The sample (N=101) had a mean age of 36.8 years (SD 10.0), and 75.2% (76/101) of the participants were female, 78.2% (79/101) were non-Hispanic White, and 72.3% (73/101) were employed. Participants' W-SUDs use averaged 15.7 (SD 14.2) days, 12.1 (SD 8.3) modules, and 600.7 (SD 556.5) sent messages. About 94% (562/598) of all completed psychoeducational lessons were rated positively. From treatment start to end, in-app craving ratings were reduced by half (87/101, 86.1% reporting cravings in the app; odds ratio 0.48, 95% CI 0.32-0.73). Posttreatment assessment completion was 50.5% (51/101), with better retention among those who initially screened higher on substance misuse. From pre- to posttreatment, confidence to resist urges to use substances significantly increased (mean score change +16.9, SD 21.4; P<.001), whereas past month substance use occasions (mean change -9.3, SD 14.1; P<.001) and scores on the Alcohol Use Disorders Identification Test-Concise (mean change -1.3, SD 2.6; P<.001), 10-item Drug Abuse Screening Test (mean change -1.2, SD 2.0; P<.001), Patient Health Questionnaire-8 item (mean change 2.1, SD 5.2; P=.005), Generalized Anxiety Disorder-7 (mean change -2.3, SD 4.7; P=.001), and cravings scale (68.6% vs 47.1% moderate to extreme; P=.01) significantly decreased. Most participants would recommend W-SUDs to a friend (39/51, 76%) and reported receiving the service they desired (41/51, 80%). Fewer felt W-SUDs met most or all of their needs (22/51, 43%). CONCLUSIONS: W-SUDs was feasible to deliver, engaging, and acceptable and was associated with significant improvements in substance use, confidence, cravings, depression, and anxiety. Study attrition was high. Future research will evaluate W-SUDs in a randomized controlled trial with a more diverse sample and with the use of greater study retention strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04096001; http://clinicaltrials.gov/ct2/show/NCT04096001.

A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa.

OBJECTIVE: Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administration (FDA) approved for obesity, has utility for binge eating. With no randomized controlled trials (RCTs) yet performed, this trial aimed to evaluate PHEN/TPM-ERs efficacy and safety in a crossover RCT for patients with binge-eating disorder (BED) or bulimia nervosa (BN). METHOD: Participants were randomized to 12-weeks PHEN/TPM-ER (3.75 mg/23 mg-15 mg/92 mg) or placebo followed by 2-weeks drug washout, then 12-week crossover. Demographics, vitals, eating disorder behaviors, mood, and side effects were measured. Primary outcome was objective binge-eating (OBE) days/4-weeks; secondary outcomes included binge abstinence. Mixed-effect models estimated treatment effects, with fixed effects adjusting for treatment, study period, and diagnosis. RESULTS: The 22 adults (BED = 18, BN = 4) were female (96%), Caucasian (55%), aged 42.9 (SD = 10.1) years with body mass index = 31.1 (SD = 6.2) kg/m2 . Baseline OBE days/4-weeks decreased from 16.2 (SD = 7.8) to 4.2 (SD = 8.4) after PHEN/TPM-ER versus 13.2 (SD = 9.1) after placebo (p < .0001), with abstinence rates = 63.6% on PHEN/TPM-ER versus 9.1% on placebo (p < .0001). Weight changes = -5.8 kg on PHEN/ TPM-ER versus +0.4 kg on placebo. Drop-out = 2 (9%) on PHEN/TPM-ER and 2 (9%) on placebo, with few side effects. Vital sign changes with PHEN/TPM-ER were minimal and similar to placebo. Responses were not significantly different for BED versus BN. DISCUSSION: This first RCT to evaluate the efficacy and safety of PHEN/TPM-ER for BED/BN found this drug combination significantly more effective at reducing binge eating than placebo and well tolerated. However, with only four participants with BN, findings regarding the safety of PHEN/TPM-ER in patients with BN must be taken with caution. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.

Are parental self-efficacy and family flexibility mediators of treatment for anorexia nervosa?

OBJECTIVE: Family-based treatment (FBT) for adolescent anorexia nervosa (AN) promotes faster weight restoration when compared to other treatments. However, the mechanisms through which this occurs are not clarified. This study explored the trajectories of parental self-efficacy and perceived family flexibility during FBT and systemic family therapy (SyFT). We also explored whether parental self-efficacy mediates the effects of treatment on weight gain early in treatment. METHOD: 158 adolescents (12-18 years old; 89% girls) and their parents were randomized to FBT or SyFT. Parental self-efficacy as well as adolescents' and parental perceptions of the family's flexibility were collected at baseline and at sessions 2, 4, 6, and 8. RESULTS: Over time, only parents in FBT reported significantly greater self-efficacy. The change in maternal self-efficacy over the first 8 weeks of treatment was a significant mediator of session 10 weight gain. There were no significant group differences in perceived flexibility by session 8. DISCUSSION: Both parents in FBT and mothers in SyFT understand early the need to change their family's rules and roles. However, the specific strategies of FBT appear to mediate early weight gain in AN.

Does family-based treatment reduce the need for hospitalization in adolescent anorexia nervosa?

OBJECTIVE: We examined the timing and number of days of hospitalization during the course of treatment, hospitalization effects on outcome, and predictors and moderators of the use of hospitalization in adolescents with anorexia nervosa (AN). METHOD: Data used in this study were collected from 158 adolescents (ages 12 to 18 years of age) who met DSM-IVTR criteria for AN (exclusive of the amenorrhea criteria) randomized to receive either Family Based Treatment (FBT) or Systemic Family Therapy (SyFT) in a 7 site study. RESULTS: The trajectory of hospital day use is similar in the first 5 weeks irrespective of treatment allocation. However, days of hospitalization continued to increase throughout SyFT but leveled off in FBT after ∼5 weeks of treatment. Early hospitalization was a negative predictor for improvements in percent weight change for both treatment groups (t(1)=2.6, p = 0.011). Co-morbid psychopathology predicted early hospital use in both treatments. Higher levels of eating related obsessions and depression moderated hospitalization rates suggesting that FBT reduces early hospitalization rates compared to SyFT for these subgroups. DISCUSSION: These data support and extend findings from previous studies by identifying patterns of hospital use, and predictors and moderators of treatment effect for early hospitalization use in adolescent AN. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:891-894).

Common practices for sociodemographic data reporting in digital mental health intervention research: a scoping review.

BACKGROUND: The ability of digital mental health interventions (DMHIs) to reduce mental health disparities relies on the recruitment of research participants with diverse sociodemographic and self-identity characteristics. Despite its importance, sociodemographic reporting in research is often limited, and the state of reporting practices in DMHI research in particular has not been comprehensively reviewed. OBJECTIVES: To characterise the state of sociodemographic data reported in randomised controlled trials (RCTs) of app-based DMHIs published globally from 2007 to 2022. METHODS: A scoping review of RCTs of app-based DMHIs examined reporting frequency for 16 sociodemographic domains (eg, gender) and common category options within each domain (eg, woman). The search queried five electronic databases. 5079 records were screened and 299 articles were included. RESULTS: On average, studies reported 4.64 (SD=1.79; range 0-9) of 16 sociodemographic domains. The most common were age (97%) and education (67%). The least common were housing situation (6%), residency/location (5%), veteran status (4%), number of children (3%), sexual orientation (2%), disability status (2%) and food security (<1%). Gender or sex was reported in 98% of studies: gender only (51%), sex only (28%), both (<1%) and gender/sex reported but unspecified (18%). Race or ethnicity was reported in 48% of studies: race only (14%), ethnicity only (14%), both (10%) and race/ethnicity reported but unspecified (10%). CONCLUSIONS: This review describes the widespread underreporting of sociodemographic information in RCTs of app-based DMHIs published from 2007 to 2022. Reporting was often incomplete (eg, % female only), unclear (eg, the conflation of gender/sex) and limited (eg, only options representing majority groups were reported). Trends suggest reporting has somewhat improved in recent years. Diverse participant populations must be welcomed and described in DMHI research to broaden learning and the generalisability of results, a prerequisite of DMHI's potential to reduce disparities in mental healthcare.

A relational agent for treating substance use in adults: Protocol for a randomized controlled trial with a psychoeducational comparator.

BACKGROUND: Substance use disorders (SUDs) are prevalent and compromise health and wellbeing. Scalable solutions, such as digital therapeutics, may offer a population-based strategy for addressing SUDs. Two formative studies supported the feasibility and acceptability of the relational agent Woebot, an animated screen-based social robot, for treating SUDs (W-SUDs) in adults. Participants randomized to W-SUDs reduced their substance use occasions from baseline to end-of-treatment (EOT) relative to a waitlist control. OBJECTIVE: To further develop the evidence base, the current randomized trial extends follow-up to 1-month post-treatment and will test the efficacy of W-SUDs relative to a psychoeducational control. METHODS: This study will recruit, screen, and consent 400 adults online reporting problematic substance use. Following baseline assessment, participants will be randomized to 8 weeks of W-SUDs or a psychoeducational control. Assessments will be conducted at weeks 4, 8 (EOT), and 12 (1-month post-treatment). Primary outcome is past-month number of substance use occasions, summed across all substances. Secondary outcomes are number of heavy drinking days, the percent of days abstinent from all substances, substance use problems, thoughts about abstinence, cravings, confidence to resist substance use, symptoms of depression and anxiety, and work productivity. If significant group differences are found, we will explore moderators and mediators of treatment effects. CONCLUSIONS: The current study builds upon emerging evidence of a digital therapeutic for reducing problematic substance use by examining sustained effects and testing against a psychoeducational control condition. If efficacious, the findings have implications for scalable mobile health interventions for reducing problematic substance use. TRIAL REGISTRATION: NCT04925570.

Associations Between Substance Use Problems and Stress During COVID-19.

OBJECTIVE: The COVID-19 pandemic has produced major life disruptions and increased stress. We explored associations between pandemic-related stress and substance use problems. METHOD: Adults (N = 180; 65% female) with problematic substance use (CAGE-AID > 1) were recruited online June-August 2020. Measures included the 15-item Short Inventory of Problems-Alcohol and Drugs (SIP-AD), Generalized Anxiety Disorder-7 (GAD-7) seven-item anxiety measure, Patient Health Questionnaire-8 (PHQ-8) eight-item depression measure, a three-item measure of pandemic life disruptions, a six-item measure of pandemic-related mental health effects, and a five-item measure of pandemic-related personal growth. Participants reported whether they frequented bars and attended large gatherings. Participants with children (<18 years of age) in the home completed a four-item measure of pandemic-related worry about children's well-being. Pandemic-related measures with significant bivariate associations with SIP-AD, GAD, and PHQ scores were tested in multivariable linear regression, adjusting for sex, age, and race/ethnicity. RESULTS: Participants who struggled with responsibilities at home, had greater mental health impacts, had greater personal growth, and frequented bars or large gatherings had higher SIPAD scores (all ps < .05). Participants who struggled with responsibilities at home, had difficulty getting necessities, had greater mental health impacts, and worried more about their children had higher GAD-7 and PHQ-8 scores (all ps < .05). Participants who lost a job or income during the pandemic had higher PHQ-8 scores (p = .015). In multivariable analyses, greater mental health impacts were associated with higher SIP-AD, PHQ-8, and GAD-7 scores (all ps < .05). CONCLUSIONS: Experiencing worsened mental health symptoms during COVID-19 was associated with more substance use problems and symptoms of depression and anxiety. Pandemic disruptions may exacerbate preexisting substance use problems.

A randomized controlled trial of a therapeutic relational agent for reducing substance misuse during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic disrupted access to treatment for substance use disorders (SUDs), while alcohol and cannabis retail sales increased. During the pandemic, we tested a tailored digital health solution, Woebot-SUDs (W-SUDs), for reducing substance misuse. METHODS: In a randomized controlled trial, we compared W-SUDs for 8 weeks to a waitlist control. U.S. adults (N = 180) who screened positive for substance misuse (CAGE-AID>1) were enrolled June-August 2020. The primary outcome was the change in past-month substance use occasions from baseline to end-of-treatment (EOT). Study retention was 84%. General linear models tested group differences in baseline-to-EOT change scores, adjusting for baseline differences and attrition. RESULTS: At baseline, the sample (age M = 40, SD = 12, 65% female, 68% non-Hispanic white) averaged 30.2 (SD = 18.6) substance occasions in the past month. Most (77%) reported alcohol problems, 28% cannabis, and 45% multiple substances; 46% reported moderate-to-severe depressive symptoms. Treatment participants averaged 920 in-app text messages (SD = 892, Median = 701); 96% of completed lessons were rated positively; and 88% would recommend W-SUDs. Relative to waitlist, W-SUDs participants significantly reduced past-month substance use occasions (M = -9.1, SE = 2.0 vs. M = -3.3, SE = 1.8; p = .039). Secondary substance use and mood outcomes did not change significantly by group; however, reductions in substance use occasions correlated significantly with increased confidence and fewer substance use problems, cravings, depression and anxiety symptoms, and pandemic-related mental health effects (p-value<.05). CONCLUSIONS: W-SUDs was associated with significant reductions in substance use occasions. Reduction in substance use occasions was associated with better outcomes, including improved mental health. W-SUDs satisfaction was high.