Adaptive treatment strategies in internet-delivered Cognitive behavior therapy : predicting and avoiding treatment failures

Background: Internet-delivered Cognitive Behavior Therapy (ICBT) is efficacious for a number of psychiatric disorders and can be successfully implemented in routine psychiatric care. Still, only about half of patients experience a good enough treatment outcome. Using data from the early part of treatment to identify patients with high risk of not benefitting from it, and target them with additional resources to prevent the predicted failure is a potential way forward. We call this an Adaptive Treatment Strategy, and a very important part of it is the ability to predict the outcome for a specific patient. Aims: To establish a proof of concept for an Adaptive Treatment Strategy in ICBT, and explore outcome prediction further by evaluating the accuracy of an empirically supported classification algorithm, the time point in treatment when acceptable accuracy can be reached, and the accuracy of ICBT-therapists’ own predictions. Preliminary benchmarks regarding the clinical usefulness of prediction will be established. Studies: Four studies were performed: Study I was a randomized controlled trial (RCT; n=251) where patients’ risk of treatment Failure (Red=high risk of failure, Green=low risk) was predicted during week 4 out of 9 in ICBT for Insomnia. Red patients (n=102) were then randomized to either continuing with standard treatment (n=51) or having their treatment individually adapted (n=51). In Study II, the classification algorithm from Study I was evaluated in terms of classification accuracy and the contribution of the different predictors used. In Study III, data from 4310 regular care ICBT-patients having received treatment for either Depression, Social anxiety disorder or Panic disorder were analyzed in a series of multiple regression models using weekly observations of the primary symptom measure as predictors to classify risk of Failure. As a contrast, Study IV examines ICBT therapists’ own predictions on both categorical and continuous treatment outcomes, as they made predictions for each of their patients (n=897) during week 4 in the same three treatments as in Study III. Results: The RCT was successful in that Red patients receiving Adapted treatment improved significantly more than Red patients receiving standard treatment, and their odds of failure were nearly cut in half. Green patients did better than Red patients, indicating that the accuracy of the classification algorithm was clinically useful. Study II showed that the balanced accuracy of the classifier was 67% and that only 11 of 21 predictors correlated significantly with Failure. Notable predictors were symptom levels as well as different markers of treatment engagement. Study III and IV showed that acceptable predictions could be made halfway through treatment using only symptom scores and basic statistics, and that ICBT-therapists predicted outcomes better than chance but on average 9.5 % less accurate than the statistical models. Therapist predictions reached the clinical acceptance benchmark only for remission in Social anxiety disorder. At treatment week four, therapist could predict on average 16% of the variance in continuous outcomes, compared to a statistical model explaining 39%. Conclusions: We find support for the clinical usefulness of an Adaptive Treatment Strategy in ICBT for insomnia, and establish a preliminary benchmark that a classification algorithm with at least 67% balanced accuracy should be sufficient for clinical purposes. Simple statistical models using only symptom scores can reach clinically acceptable levels of accuracy halfway through 12-week ICBT-programs. Previous findings that therapists’ predictions are less accurate than statistical models seem to hold also for therapists providing ICBT. However, it was also indicated that clinicians’ ratings of adherence and activity do add unique information to prediction algorithms. In line with previous findings, the vast majority of useful prediction variables were found during early treatment, rather than before treatment start

Predicting Treatment Outcomes in Guided Internet-Delivered Therapy for Anxiety Disorders—The Role of Treatment Self-Efficacy

Aim: Guided Internet-delivered therapy has shown to be an effective treatment format for anxiety disorders. However, not all patients experience improvement, and although predictors of treatment outcome have been identified, few are consistent over time and across studies. The current study aimed to examine whether treatment self-efficacy (self-efficacy regarding the mastery of obstacles during treatment) in guided Internet-delivered therapy for anxiety disorders in adults could be a predictor of lower dropout rates and greater symptom reduction. Method: The analyzed data comes from an open effectiveness study including 575 patients receiving guided Internet-delivered therapy for panic disorder or social anxiety disorder. Treatment self-efficacy was measured at pre-treatment. Symptom reduction was measured at 10 measurement points, including a 6-month follow-up. A mixed linear model was applied in the analysis. Results: The results showed that high treatment self-efficacy was a predictor of both lower dropout rates and greater symptom reduction. Significant interaction effects between time and treatment self-efficacy were found for several of the nine modules that constitutes the treatment program, suggesting that treatment self-efficacy could be a moderator of symptom reduction. Three of nine modules in the panic disorder treatment and six of nine in the social anxiety disorder treatment showed significant interaction effects. Conclusion: The results suggest that measuring treatment self-efficacy may be a valuable tool to identify patients at risk of dropping out, and that treatment self-efficacy could be a predictor and moderator of symptom reduction in guided Internet-delivered therapy. The implications of the results are discussed.publishedVersio

Expectancies, working alliance, and outcome in transdiagnostic and single diagnosis treatment for anxiety disorders: an investigation of mediation

Patients’ outcome expectancies and the working alliance are two psychotherapy process variables that researchers have found to be associated with treatment outcome, irrespective of treatment approach and problem area. Despite this, little is known about the mechanisms accounting for this association, and whether contextual factors (e.g., psychotherapy type) impact the strength of these relationships. The primary aim of this study was to examine whether patient-rated working alliance quality mediates the relationship between outcome expectancies and pre- to post-treatment change in anxiety symptoms using data from a recent randomized clinical trial comparing a transdiagnostic treatment (the Unified Protocol [UP]; Barlow et al., Unified protocol for transdiagnostic treatment of emotional disorders: Client workbook, Oxford University Press, New York, 2011a; Barlow et al., Unified protocol for transdiagnostic treatment of emotional disorders: Patient workbook. New York: Oxford University Press, 2017b) to single diagnosis protocols (SDPs) for patients with a principal heterogeneous anxiety disorder (n = 179). The second aim was to explore whether cognitive-behavioral treatment condition (UP vs. SDP) moderated this indirect relationship. Results from mediation and moderated mediation models indicated that, when collapsing across the two treatment conditions, the relationship between expectancies and outcome was partially mediated by the working alliance [B = 0.037, SE = 0.05, 95% CI (.005, 0.096)]. Interestingly, within-condition analyses showed that this conditional indirect effect was only present for SDP patients, whereas in the UP condition, working alliance did not account for the association between expectancies and outcome. These findings suggest that outcome expectancies and working alliance quality may interact to influence treatment outcomes, and that the nature and strength of the relationships among these constructs may differ as a function of the specific cognitive-behavioral treatment approach utilized.This study was funded by grant R01 MH090053 from the National Institutes of Health. (R01 MH090053 - National Institutes of Health)First author draf

For whom does it work? Moderators of outcome on the effect of a transdiagnostic internet-based maintenance treatment after inpatient psychotherapy: Randomized controlled trial

Background: Recent studies provide evidence for the effectiveness of Internet-based maintenance treatments for mental disorders. However, it is still unclear which participants might or might not profit from this particular kind of treatment delivery. Objective: The study aimed to identify moderators of treatment outcome in a transdiagnostic Internet-based maintenance treatment (TIMT) offered to patients after inpatient psychotherapy for mental disorders in routine care. Methods: Using data from a randomized controlled trial (N=400) designed to test the effectiveness of TIMT, we performed secondary analyses to identify factors moderating the effects of TIMT (intervention) when compared with those of a treatment-as-usual control condition. TIMT involved an online self-management module, asynchronous patient-therapist communication, a peer support group, and online-based progress monitoring. Participants in the control condition had unstructured access to outpatient psychotherapy, standardized outpatient face-to-face continuation treatment, and psychotropic management. Self-reports of psychopathological symptoms and potential moderators were assessed at the start of inpatient treatment (T1), at discharge from inpatient treatment/start of TIMT (T2), and at 3-month (T3) and 12-month follow-up (T4). Results: Education level, positive outcome expectations, and diagnoses significantly moderated intervention versus control differences regarding changes in outcomes between T2 and T3. Only education level moderated change differences between T2 and T4. The effectiveness of the intervention (vs control) was more pronounced among participants with a low (vs high) education level (T2-T3: B=-0.32, SE 0.16, P=.049; T2-T4: B=-0.42, SE 0.21, P=.049), participants with high (vs low) positive outcome expectations (T2-T3: B=-0.12, SE 0.05, P=.02) and participants with anxiety disorder (vs mood disorder) (T2-T3: B=-0.43, SE 0.21, P=.04). Simple slope analyses revealed that despite some subgroups benefiting less from the intervention than others, all subgroups still benefited significantly. Conclusions: This transdiagnostic Internet-based maintenance treatment might be suitable for a wide range of participants differing in various clinical, motivational, and demographic characteristics. The treatment is especially effective for participants with low education levels. These findings may generalize to other Internet-based maintenance treatments. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 28632626; http://www.controlled-trials.com/isrctn/pf/ 28632626 (Archived by WebCite at http://www.webcitation.org/6IqZjTLrx). © David Daniel Ebert, Mario Gollwitzer, Heleen Riper, Pim Cuijpers, Harald Baumeister, Matthias Berking

What makes cognitive behavior therapy work? An investigation of psychological and inflammatory processes

Background: Common mental disorders (CMDs; anxiety disorders, depression, insomnia and stress-related disorders) cause significant suffering, reduced functioning and impaired quality of life. Cognitive behavior therapy (CBT) is an effective treatment, but there is considerable room for improvements in outcomes. Increased knowledge regarding potential mechanisms of change in CBT could inform treatment development. Investigation of both psychological and inflammatory processes could be one way of moving the field forward. Aims: The aim of this thesis was to investigate processes and correlates of therapeutic change in CBT for CMDs. Based on two clinical trials set in primary care in which CBT for CMDs were tested (Study I and II), this thesis investigated mediators of change in CBT for exhaustion disorder (Study III), processes of change in CBT for social anxiety disorder (Study IV), and inflammatory correlates of change in CBT for CMDs (Study V). Methods: In the clinical trials (Study I, N = 211; and Study II, N = 396), primary care patients with CMDs were treated with CBT, delivered in different formats. Based on the effects found in these trials, further analyzes were conducted in Study III, IV and V, with regard to processes related to outcome. In Study III, mediators of change were analyzed in patients with a primary exhaustion disorder (N = 82), randomized to CBT or another active psychological treatment. In Study IV, the effect of changes in proposed maintaining processes were analyzed in relation to symptom change in guided self-help CBT for social anxiety disorder (N = 61). In Study V, inflammatory cytokines were measured before and after treatment with CBT and analyzed in relation to psychiatric symptoms (N = 367). Results: The results of the clinical trials (Study I and II) showed beneficial effects of disorder-specific CBT for CMDs. In Study III, CBT led to larger effects on symptoms of exhaustion than the comparator, and this difference in effects was mediated by improvements in sleep quality and perceived competence. In Study IV, several of the putative change processes (i.e., estimated probability and cost of negative social events, self-focused attention, avoidance, and safety behaviors) predicted subsequent changes in social anxiety. However, all of these processes except for avoidance were also predicted by prior symptom reduction. In Study V, we found no robust associations across the study sample between inflammatory cytokines and psychiatric symptom severity. Further, the marked symptom improvement was not tracked by reductions in cytokines. Conclusions: CBT for patients with CMDs in primary care yielded favorable effects on psychiatric symptoms. In CBT for exhaustion disorder, sleep disturbance and perceived competence may be important treatment targets. In social anxiety disorder, several of the proposed maintaining processes seem to be part of positive reciprocal cycles, where improvements in processes and symptoms influence each other. Avoidance showed a unidirectional effect on subsequent symptoms and might thus be of specific clinical relevance. The results also suggest a limited role of inflammatory processes in symptomatic improvements following CBT for CMDs

Who benefits from guided internet-based interventions? A systematic review of predictors and moderators of treatment outcome

To our knowledge, no systematic review has been conducted on predictors or moderators of treatment outcome across diagnoses in guided internet-based interventions (IBIs) for adults. To identify who benefits from this specific format and therein inform future research on improving patient-treatment fit, we aimed to aggregate results of relevant studies. 2100 articles, identified by searching the databases PsycInfo, Ovid Medline, and Pubmed and through snowballing, were screened in April/May 2021 and October 2022. Risk of bias and intra- and interrater reliability were assessed. Variables were grouped by predictor category, then synthesized using vote counting based on direction of effect. N = 60 articles were included in the review. Grouping resulted in 88 predictors/moderators, of which adherence, baseline symptoms, education, age, and gender were most frequently assessed. Better adherence, treatment credibility, and working alliance emerged as conclusive predictors/moderators for better outcome, whereas higher baseline scores predicted more reliable change but higher post-treatment symptoms. Results of all other predictors/moderators were inconclusive or lacked data. Our review highlights that it is currently difficult to predict, across diagnoses, who will benefit from guided IBIs. Further rigorous research is needed to identify predictors and moderators based on a sufficient number of studies. PROSPERO registration: CRD42021242305

Predicting response to transdiagnostic iCBT for emotional disorders from patient and therapist involvement

Background Transdiagnostic iCBT has been shown to be effective for the treatment of emotional disorders. Less is known about the optimal level of therapist and patient involvement in these interventions. Specific characteristics of Internet-delivered interventions include treatment adherence (e.g., amount of review of the materials) and guidance (e.g., amount of therapist support). Exploring the importance of these elements in treatment outcome may help to maximize the efficiency of Internet-delivered psychological interventions. Aim In this study, we aimed to analyze the relationship between patient and therapist involvement (i.e., platform usage and amount of therapist guidance) in a sample of patients with emotional disorders who received transdiagnostic iCBT in Spanish public specialized mental healthcare services. Method This is a secondary analysis of a randomized controlled trial. The sample included 63 patients who completed transdiagnostic iCBT for emotional disorders. Platform usage metrics included number of logins into the platform and number of times the participants reviewed the modules. Therapist guidance was measured as the number of support phone calls with a therapist and their total duration (minutes). Logistic regressions and ROC analyses were performed to explore the predictive value of platform usage and therapist guidance in symptom reduction. Clinical outcomes included depressive and anxiety symptoms assessed at baseline and post-intervention. The bivariate relationship between the platform usage and therapist guidance variables was also explored. Results Overall, platform usage and therapist guidance were not associated with symptom improvement. However, the patient and therapist involvement parameters were intercorrelated. Specifically, the number of calls and their duration were associated with a greater number of logins (r = 0.61; p < .001) and more frequent reviews of the modules (0.46 ≤ r ≤ 0.60; p < .001). Higher baseline depression and anxiety were, respectively, associated with greater improvements in depression (r = −0.37, p = .003) and anxiety after treatment completion (r = −0.48, p < .001). Discussion The results suggest that there is no reliable cut-off point for platform usage and therapist guidance in predicting optimal symptom reduction. However, significant associations were found between platform usage and guidance variables that warrant additional research. More research on this topic is necessary to further clarify the role of these and other platform usage and guidance variables in Internet-delivered iCBT outcomes

The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder

<p>Abstract</p> <p>Background</p> <p>Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met) in the <it>COMT </it>gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting.</p> <p>Methods</p> <p>We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients.</p> <p>Results</p> <p>We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based) CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material.</p> <p>Conclusions</p> <p>We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed.</p> <p>Trial registration</p> <p>Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2). Registration Identification number: NCT00845260, <url>http://www.clinicaltrials.gov/ct2/show/NCT00845260</url></p