Optimizing Outcomes in Psychotherapy for Anxiety Disorders Using Smartphone-Based and Passive Sensing Features: Protocol for a Randomized Controlled Trial

Background Psychotherapies, such as cognitive behavioral therapy (CBT), currently have the strongest evidence of durable symptom changes for most psychological disorders, such as anxiety disorders. Nevertheless, only about half of individuals treated with CBT benefit from it. Predictive algorithms, including digital assessments and passive sensing features, could better identify patients who would benefit from CBT, and thus, improve treatment choices. Objective This study aims to establish predictive features that forecast responses to transdiagnostic CBT in anxiety disorders and to investigate key mechanisms underlying treatment responses. Methods This study is a 2-armed randomized controlled clinical trial. We include patients with anxiety disorders who are randomized to either a transdiagnostic CBT group or a waitlist (referred to as WAIT). We index key features to predict responses prior to starting treatment using subjective self-report questionnaires, experimental tasks, biological samples, ecological momentary assessments, activity tracking, and smartphone-based passive sensing to derive a multimodal feature set for predictive modeling. Additional assessments take place weekly at mid- and posttreatment and at 6- and 12-month follow-ups to index anxiety and depression symptom severity. We aim to include 150 patients, randomized to CBT versus WAIT at a 3:1 ratio. The data set will be subject to full feature and important features selected by minimal redundancy and maximal relevance feature selection and then fed into machine leaning models, including eXtreme gradient boosting, pattern recognition network, and k-nearest neighbors to forecast treatment response. The performance of the developed models will be evaluated. In addition to predictive modeling, we will test specific mechanistic hypotheses (eg, association between self-efficacy, daily symptoms obtained using ecological momentary assessments, and treatment response) to elucidate mechanisms underlying treatment response. Results The trial is now completed. It was approved by the Cantonal Ethics Committee, Zurich. The results will be disseminated through publications in scientific peer-reviewed journals and conference presentations. Conclusions The aim of this trial is to improve current CBT treatment by precise forecasting of treatment response and by understanding and potentially augmenting underpinning mechanisms and personalizing treatment. Trial Registration ClinicalTrials.gov NCT03945617; https://clinicaltrials.gov/ct2/show/results/NCT03945617 International Registered Report Identifier (IRRID) DERR1-10.2196/4254

Anticipating control over aversive stimuli is mediated by the medial prefrontal cortex: An fMRI study with healthy adults

The anticipation of control over aversive events in life is relevant for our mental health. Insights on the underlying neural mechanisms remain limited. We developed a new functional magnetic resonance imaging (fMRI) task that uses auditory stimuli to explore the neural correlates of (1) the anticipation of control over aversion and (2) the processing of aversion. In a sample of 25 healthy adults, we observed increased neural activation in the medial prefrontal cortex (ventromedial prefrontal cortex and rostral anterior cingulate cortex), other brain areas relevant for reward anticipation (ventral striatum, brainstem [ventral tegmental area], midcingulate cortex), and the posterior cingulate cortex when they anticipated control over aversion compared with anticipating no control (1). The processing of aversive sounds compared to neutral sounds (2) was associated with increased neural activation in the bilateral posterior insula. Our findings provide evidence for the important role of medial prefrontal regions in control anticipation and highlight the relevance of conceiving the neural mechanisms involved within a reward-based framework

A systematic review and meta-analysis of transdiagnostic cognitive behavioural therapies for emotional disorders.

Transdiagnostic cognitive behavioural psychotherapy (TD-CBT) may facilitate the treatment of emotional disorders. Here we investigate short- and long-term efficacy of TD-CBT for emotional disorders in individual, group and internet-based settings in randomized controlled trials (PROSPERO CRD42019141512). Two independent reviewers screened results from PubMed, MEDLINE, PsycINFO, Google Scholar, medRxiv and OSF Preprints published between January 2000 and June 2023, selected studies for inclusion, extracted data and evaluated risk of bias (Cochrane risk-of-bias tool 2.0). Absolute efficacy from pre- to posttreatment and relative efficacy between TD-CBT and control treatments were investigated with random-effects models. Of 56 identified studies, 53 (6,705 participants) were included in the meta-analysis. TD-CBT had larger effects on depression (g = 0.74, 95% CI = 0.57-0.92, P < 0.001) and anxiety (g = 0.77, 95% CI = 0.56-0.97, P < 0.001) than did controls. Across treatment formats, TD-CBT was superior to waitlist and treatment-as-usual. TD-CBT showed comparable effects to disorder-specific CBT and was superior to other active treatments for depression but not for anxiety. Different treatment formats showed comparable effects. TD-CBT was superior to controls at 3, 6 and 12 months but not at 24 months follow-up. Studies were heterogeneous in design and methodological quality. This review and meta-analysis strengthens the evidence for TD-CBT as an efficacious treatment for emotional disorders in different settings

Short- and Long-term Efficacy of Transdiagnostic Cognitive Behavioral Therapies for Emotional Disorders: Systematic Review and Meta-Analysis

Transdiagnostic cognitive-behavioral psychotherapy (TD-CBT) may facilitate treatment of emotional disorders. We investigate short- and long-term efficacy of TD-CBT for emotional disorders in individual, group, and Internet-based settings in randomized controlled trials (PROSPERO CRD42019141512). Two independent reviewers screened results from PubMed, MEDLINE, PsycINFO, Google Scholar, medRxiv, and OSF Preprints published between January 2000 and January 2023, selected studies for inclusion, extracted data and evaluated risk of bias (Cochrane risk-of-bias tool 2.0). Absolute efficacy from pre- to post-treatment and relative efficacy between TD-CBT and control treatments were investigated with random-effects models. Of 56 identified studies, 53 (6610 participants) were included in the meta-analysis. TD-CBT had large effects on depression (d = 1.15, 95%CI = 1.03 - 1.28) and anxiety (d = 1.08, 95%CI = 0.95 - 1.21), from pre- to post treatment. Across treatment formats, TD-CBT was superior to waitlist (depression: g = 1.31, 95%CI = 0.88 - 1.74; anxiety: g = 1.22, 95%CI = 0.82 - 1.63) and treatment-as-usual (depression: g = 0.87, 95%CI = 0.63 - 1.11; anxiety: g = 0.94, 95%CI = 0.57 - 1.30). TD-CBT showed comparable effects to disorder-specific treatments, with indications of TD-CBT’s superiority (depression: g = 0.16, 95%CI = 0.01 - 0.32; anxiety: g = 0.15, 95%CI = 0.04 - 0.26). Large effects were reported for Internet-based TD-CBT for up to 2 years. Studies were heterogeneous in design and methodological quality. This review and meta-analysis strengthens the evidence for TD-CBT as an efficacious treatment for emotional disorders in different settings

Self-efficacy effects on symptom experiences in daily life and early treatment success in anxiety patients

Self-efficacy is a key construct in behavioral science affecting mental health and psychopathology. Here, we expand on previously demonstrated between-persons self-efficacy effects. We prompted 66 patients five times daily for 14 days before starting cognitive behavioral therapy (CBT) to provide avoidance, hope, and perceived psychophysiological-arousal ratings. Multilevel logistic regression analyses confirmed self-efficacy’s significant effects on avoidance in daily life (odds ratio [OR] = 0.53, 95% confidence interval [CI] = [0.34, 0.84], p = .008) and interaction effects with anxiety in predicting perceived psychophysiological arousal (OR = 0.79, 95% CI = [0.62, 1.00], p = .046) and hope (OR = 1.21, 95% CI = [1.03, 1.42], p = .02). More self-efficacious patients also reported greater anxiety-symptom reduction early in treatment. Our findings assign a key role to self-efficacy for daily anxiety-symptom experiences and for early CBT success. Self-efficacy interventions delivered in patients’ daily lives could help improve treatment outcome

Optimizing Outcomes in Psychotherapy for Anxiety Disorders (OPTIMAX) Protocol– A Randomized Controlled Trial on Efficacy and Response Prediction in a Transdiagnostic Psychotherapy Treatment for Anxiety Disorders

Background: This paper describes the study protocol for our clinical trial “Optimizing Outcomes in Psychotherapy for Anxiety Disorders (OPTIMAX)” funded by the Swiss National Science Foundation (10001C_169827). The study aims to establish predictive features for forecasting response to cognitive behavior therapy (CBT) and to investigate mechanisms underlying treatment response. Methods: OPTIMAX comprises a monocentric, randomized-controlled clinical trial. We employ the Unified Treatment Protocol (UP, Barlow, 2017), an established transdiagnostic CBT protocol for treating emotional disorders, to treat patients with anxiety disorders. We use psychological questionnaires, experimental tasks, biological samples, ecological momentary assessments, activity tracking, and smartphone-based passive sensing data in order to derive a multimodal feature set for predictive modeling. We obtain assessments at different time points including baseline, mid-, and post- treatment as well as 6 and 12 months after treatment completion. Anxiety and depression symptom severity are indexed weekly during treatment. We aim to include 150 patients, randomized to CBT versus WAIT group in a 3:1 ratio. Machine learning (e.g., support vector machines, random forest) and linear regression modeling will be employed to establish predictive accuracy in forecasting treatment response. In addition to predictive modelling, we test mechanistic hypotheses, e.g., on the association between self-efficacy, dynamic symptom changes and treatment response, to elucidate mechanisms underlying treatment response. Discussion: The aim of the current trial is to improve current CBT treatment, such as the transdiagnostic unified treatment protocol employed here, by precise forecasting of treatment response and by understanding and, in the future, augmenting underpinning mechanisms and personalizing treatment. Registration: This study has been registered on clinicaltrials.gov (NCT03945617, 10 of May 2019, https://clinicaltrials.gov/ct2/show/NCT03945617

Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French-Belgian-Swiss APL group.

BACKGROUND: Reports of patients with secondary acute promyelocytic leukemia (APL) have increased in recent years, particularly for those who received treatment with mitoxantrone, and retrospective studies have suggested that their characteristics and outcomes were similar to those of patients with de novo APL. METHODS: The authors investigated patients with de novo and secondary APL who were included in the ongoing APL-2006 trial. Patients with secondary APL who were included in that trial also were compared with a previous retrospective cohort of patients with secondary APL. RESULTS: In the APL-2006 trial, 42 of 280 patients (15%) had secondary APL. Compared with the retrospective cohort, patients with secondary APL in the APL-2006 trial had a lower incidence of prior breast carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate carcinoma (26.2% vs 4.7%; P &lt; .001). Treatment of the primary tumor in the APL-2006 trial less frequently included combined radiochemotherapy (28.6% vs 47.2%; P = .044) and no mitoxantrone (0% vs 46.7%; P = .016) but more frequently included anthracyclines (53.3% vs 38.3%; P = .015). In the APL-2006 trial, patients who had secondary APL, compared with those who had de novo APL, were older (mean, 60.2 years vs 48.7 years, respectively; P &lt; .0001) but had a similar complete response rate (97.6% vs 90.3%, respectively), cumulative incidence of relapse (0% vs 1.8%, respectively), and overall survival (92.3% vs 90.9%, respectively) at 18 months. CONCLUSIONS: Although the incidence of secondary APL appears to be stable over time, evolving strategies for the treatment of primary cancers have reduced its occurrence among breast cancer patients but have increased its incidence among patients with prostate cancer. The current results confirm prospectively that patients with secondary APL have characteristics and outcomes similar to those of patients with de novo APL. Cancer 2015;121:2393-2399. © 2015 American Cancer Society