Comparison of the Working Alliance in Blended Cognitive Behavioral Therapy and Treatment as Usual for Depression in Europe: Secondary Data Analysis of the E-COMPARED Randomized Controlled Trial.

BACKGROUND: Increasing interest has centered on the psychotherapeutic working alliance as a means of understanding clinical change in digital mental health interventions in recent years. However, little is understood about how and to what extent a digital mental health program can have an impact on the working alliance and clinical outcomes in a blended (therapist plus digital program) cognitive behavioral therapy (bCBT) intervention for depression. OBJECTIVE: This study aimed to test the difference in working alliance scores between bCBT and treatment as usual (TAU), examine the association between working alliance and depression severity scores in both arms, and test for an interaction between system usability and working alliance with regard to the association between working alliance and depression scores in bCBT at 3-month assessments. METHODS: We conducted a secondary data analysis of the E-COMPARED (European Comparative Effectiveness Research on Blended Depression Treatment versus Treatment-as-usual) trial, which compared bCBT with TAU across 9 European countries. Data were collected in primary care and specialized services between April 2015 and December 2017. Eligible participants aged 18 years or older and diagnosed with major depressive disorder were randomized to either bCBT (n=476) or TAU (n=467). bCBT consisted of 6-20 sessions of bCBT (involving face-to-face sessions with a therapist and an internet-based program). TAU consisted of usual care for depression. The main outcomes were scores of the working alliance (Working Alliance Inventory-Short Revised-Client [WAI-SR-C]) and depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) at 3 months after randomization. Other variables included system usability scores (System Usability Scale-Client [SUS-C]) at 3 months and baseline demographic information. Data from baseline and 3-month assessments were analyzed using linear regression models that adjusted for a set of baseline variables. RESULTS: Of the 945 included participants, 644 (68.2%) were female, and the mean age was 38.96 years (IQR 38). bCBT was associated with higher composite WAI-SR-C scores compared to TAU (B=5.67, 95% CI 4.48-6.86). There was an inverse association between WAI-SR-C and PHQ-9 in bCBT (B=-0.12, 95% CI -0.17 to -0.06) and TAU (B=-0.06, 95% CI -0.11 to -0.02), in which as WAI-SR-C scores increased, PHQ-9 scores decreased. Finally, there was a significant interaction between SUS-C and WAI-SR-C with regard to an inverse association between higher WAI-SR-C scores and lower PHQ-9 scores in bCBT (b=-0.030, 95% CI -0.05 to -0.01; P=.005). CONCLUSIONS: To our knowledge, this is the first study to show that bCBT may enhance the client working alliance when compared to evidence-based routine care for depression that services reported offering. The working alliance in bCBT was also associated with clinical improvements that appear to be enhanced by good program usability. Our findings add further weight to the view that the addition of internet-delivered CBT to face-to-face CBT may positively augment experiences of the working alliance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02542891, https://clinicaltrials.gov/study/NCT02542891; German Clinical Trials Register DRKS00006866, https://drks.de/search/en/trial/DRKS00006866; Netherlands Trials Register NTR4962, https://www.onderzoekmetmensen.nl/en/trial/25452; ClinicalTrials.Gov NCT02389660, https://clinicaltrials.gov/study/NCT02389660; ClinicalTrials.gov NCT02361684, https://clinicaltrials.gov/study/NCT02361684; ClinicalTrials.gov NCT02449447, https://clinicaltrials.gov/study/NCT02449447; ClinicalTrials.gov NCT02410616, https://clinicaltrials.gov/study/NCT02410616; ISRCTN Registry ISRCTN12388725, https://www.isrctn.com/ISRCTN12388725?q=ISRCTN12388725&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10; ClinicalTrials.gov NCT02796573, https://classic.clinicaltrials.gov/ct2/show/NCT02796573. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-016-1511-1.

Effectiveness of and processes related to internet-delivered acceptance and commitment therapy for adolescents with anxiety disorders: a randomized controlled trial.

Early access to evidence-based help is crucial for adolescents with anxiety disorders. Internet-delivered acceptance and commitment therapy (iACT) may offer adolescents increased access to care and more flexibility in engaging with treatment when and how they prefer. Process-based therapies, such as ACT, focus on theoretically derived and empirically tested key mechanisms in treatment that enable change. This study aimed to investigate the effectiveness of iACT for adolescents with anxiety disorders. The study also assessed the relationship between psychological flexibility and treatment outcomes and the relationship between participating adolescents' and therapists' perceived alliance and treatment outcomes. This was a randomized controlled trial comparing a 10-week intervention group with a wait-list control group. The 52 participants, aged 15 to 19, were recruited from all over Sweden. The treatment was effective in increasing quality of life and psychological flexibility, with moderate between-group effect sizes based on observed values. Changes in psychological flexibility was associated with changes in anxiety symptoms. The results further showed a statistically significant between-group difference in post-treatment diagnoses. No significant time per group interaction was found for anxiety symptoms, as both groups improved. Working alliance was rated as high by both participating adolescents and therapists but showed no significant relationship with treatment outcomes. Participants found the treatment an acceptable intervention. This study shows promising results for iACT in treating adolescents with anxiety disorders. The results suggest the model of psychological flexibility as an important process of change in treatment outcomes. Future research should validate these findings in larger samples and clinical contexts.

Free choice of treatment content, support on demand and supervision in internet-delivered CBT for adults with depression: A randomized factorial design trial.

Even if much is known regarding the effects of internet-delivered cognitive behaviour therapy (ICBT) for depression there are several topics that have not been studied. In this factorial design trial with 197 participants we investigated if clients in ICBT could select treatment modules themselves based on a selection of 15 tailored treatment modules developed for use in ICBT for depression. We contrasted this against clinician-tailored module selection. We also investigated if support on demand (initiated by the client) could work as well as scheduled support. Finally, we tested if clients that were mentioned in supervision would improve more than clients not mentioned (with the exception of acute cases). The treatment period lasted for 10 weeks, and we measured effects at post-treatment and two-year follow-up. Measures of depression and secondary outcomes were collected at pre-treatment, post-treatment and two-year follow-up. Overall, within-group effects were large across conditions (e.g., d = 1.73 on the BDI-II). We also found a small but significant difference in favour of self-tailored treatment over clinician-tailored (d = 0.26). Within-group effects for the secondary measures were all moderate to large including a test of knowledge about CBT. The other two contrasts "support on demand" and "supervision" yielded mostly non-significant differences, with the exception of a larger dropout rate in the support on demand condition. There were few negative effects (2.2%). Effects were largely maintained at a two-year follow-up. We conclude that clients can choose treatment modules and that support on demand may work. The role of supervision is not yet clear as advice can be transferred across clients.

Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis.

Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.

Transitioning from face-to-face treatment to iCBT for youths in primary care - therapists' attitudes and experiences.

BACKGROUND: To address the increasing mental health problems among young people, health care needs to broaden the spectrum of interventions and increase access to care. One particularly promising first-line intervention is cognitive behavioral therapy (CBT) delivered via the Internet (iCBT). The outbreak of the Coronavirus disease -2019 (COVID -19) has made the need for solid digital mental health care systems clear. This is the first published study exploring the transition among therapists of working with face-to-face treatment to using iCBT for youths suffering from anxiety treated in primary care. METHODS: Fourteen primary care therapists were included in the study. Semi-structured interviews (n = 26) were conducted on two occasions: before starting to use iCBT for youths, and at a subsequent follow-up after gaining treatment experience. Data was summarized into thematic categories. RESULTS: The overarching themes that were identified were: Attitudes to iCBT before and after implementation; Experiences of treatment delivery; Characteristics of "the right patient;" and The role of the digital therapist. CONCLUSION: The participants generally had positive attitudes to iCBT for youths and saw it as a valuable alternative to face-to-face treatments. However, they identified challenges related to patient selection, and to motivating patients and maintaining a therapeutic relationship through mainly written communication. The participants appreciated the increase in variety that iCBT brought to their schedules, and also experienced iCBT as a relief from common challenges of therapeutic work, such as emotional stress and high cognitive demands. The participating therapists' positive experiences support the introduction of iCBT for youths in routine primary care.

Working alliance as a predictor of change in depression during blended cognitive behaviour therapy.

Blended Cognitive Behaviour Therapy (bCBT) is a new form of treatment, mixing internet-based modules and face-to-face therapist sessions. How participants rate the therapeutic alliance in bCBT has not yet been thoroughly explored, and neither is it clear whether therapist- and patient-rated alliances are predictors of change in depression during treatment. Depression and alliance ratings from 73 participants in a treatment study on bCBT (part of the E-COMPARED project) were analysed using growth curve models. Alliance, as rated by both patients and therapists, was high. The therapist-rated working alliance was predictive of subsequent changes in depression scores during treatment, whereas the patient-rated alliance was not. A therapeutic alliance can be established in bCBT. The role of the therapist-rated alliance seems to be of particular importance and should be carefully considered when collecting data in future studies on bCBT.

Do guided internet-based interventions result in clinically relevant changes for patients with depression? An individual participant data meta-analysis.

Little is known about clinically relevant changes in guided Internet-based interventions for depression. Moreover, methodological and power limitations preclude the identification of patients' groups that may benefit more from these interventions. This study aimed to investigate response rates, remission rates, and their moderators in randomized controlled trials (RCTs) comparing the effect of guided Internet-based interventions for adult depression to control groups using an individual patient data meta-analysis approach. Literature searches in PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from database inception to January 1, 2016. Twenty-four RCTs (4889 participants) comparing a guided Internet-based intervention with a control group contributed data to the analysis. Missing data were multiply imputed. To examine treatment outcome on response and remission, mixed-effects models with participants nested within studies were used. Response and remission rates were calculated using the Reliable Change Index. The intervention group obtained significantly higher response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that older participants (OR = 1.01) and native-born participants (1.66) were more likely to respond to treatment compared to younger participants and ethnic minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the effects of treatment on remission.Moreover, adults with more severe depressive symptoms at baseline were more likely to remit after receiving internet-based treatment (OR = 1.19). Guided Internet-based interventions lead to substantial positive treatment effects on treatment response and remission at post-treatment. Thus, such interventions may complement existing services for depression and potentially reduce the gap between the need and provision of evidence-based treatments.

Guided and unguided Acceptance and Commitment Therapy for social anxiety disorder and/or panic disorder provided via the Internet and a smartphone application: A randomized controlled trial.

Acceptance and Commitment Therapy (ACT) can be effective in treating anxiety disorders, yet there has been no study on Internet-delivered ACT for social anxiety disorder (SAD) and panic disorder (PD), nor any study investigating whether therapist guidance is superior to unguided self-help when supplemented with a smartphone application. In the current trial, n=152 participants diagnosed with SAD and/or PD were randomized to therapist-guided or unguided treatment, or a waiting-list control group. Both treatment groups used an Internet-delivered ACT-based treatment program and a smartphone application. Outcome measures were self-rated general and social anxiety and panic symptoms. Treatment groups saw reduced general (d=0.39) and social anxiety (d=0.70), but not panic symptoms (d=0.05) compared to the waiting-list group, yet no differences in outcomes were observed between guided and unguided interventions. We conclude that Internet-delivered ACT is appropriate for treating SAD and potentially PD. Smartphone applications may partially compensate for lack of therapist support.

Internet-delivered acceptance-based behavior therapy for generalized anxiety disorder: A pilot study.

OBJECTIVE: Internet-delivered cognitive behavior therapy (ICBT) has been developed and tested for treating persons with generalized anxiety disorder (GAD). A new form of CBT focuses on acceptance (of internal experiences or difficult psychological content), mindfulness and valued actions. To date this form of CBT has not been delivered via the internet for persons with GAD. The aim of this study was to describe the functionality of a new internet-delivered acceptance-based behavior therapy for GAD, and to test the effect of the intervention in an open pilot trial. METHODS: Following exclusion of two patients we included 14 patients diagnosed with GAD from two primary care clinics. At 2-3 months follow-up after treatment 10 patients completed the outcome measures. The treatment lasted for an average of 15 weeks and consisted of acceptance-based techniques, behavior therapy components and homework assignments. RESULTS: A majority of participants completed all modules during the treatment. Findings on the Penn State Worry Questionnaire showed a within-group improvement of Cohen's d = 2.14 at posttreatment. At the follow-up results were maintained. Client satisfaction ratings were high. CONCLUSIONS: We conclude that internet-delivered acceptance-based behavior therapy potentially can be a promising new treatment for GAD. A controlled trial of the program has already been completed.

Internet-based therapy for mild to moderate depression in Swedish primary care: short term results from the PRIM-NET randomized controlled trial.

Depression presents a serious condition for the individual and a major challenge to health care and society. Internet-based cognitive behavior therapy (ICBT) is a treatment option supported in several trials, but there is as yet a lack of effective studies of ICBT in "real world" primary care settings. We examined whether ICBT differed from treatment-as-usual (TAU) in reducing depressive symptoms after 3 months. TAU comprised of visits to general practitioner, registered nurse, antidepressant drugs, waiting list for, or psychotherapy, or combinations of these alternatives. Patients, aged ≥ 18 years, who tentatively met criteria for mild to moderate depression at 16 primary care centers in the south-western region of Sweden were recruited and then assessed in a diagnostic interview. A total of 90 patients were randomized to either TAU or ICBT. The ICBT treatment included interactive elements online, a workbook, a CD with mindfulness and acceptance exercises, and minimal therapist contact. The treatment period lasted for 12 weeks after which both groups were assessed. The main outcome measure was Beck Depression Inventory-II (BDI-II). Additional measures were Montgomery Åsberg Depression Rating Scale - self rating version (MADRS-S) and Beck Anxiety Inventory (BAI). The analyses revealed no significant difference between the two groups at post treatment, neither on BDI-II, MADRS-S, nor BAI. Twenty patients (56%) in the ICBT treatment completed all seven modules. Our findings suggest that ICBT may be successfully delivered in primary care and that the effectiveness, after 3 months, is at par with TAU.

Internet-based behavioral activation and acceptance-based treatment for depression: a randomized controlled trial.

BACKGROUND: Internet-based cognitive behavior therapy for depression has been tested in several trials but there are no internet studies on behavioral activation (BA), and no studies on BA over the internet including components of acceptance and commitment therapy (ACT). The aim of this study was to develop and test the effects of internet-delivered BA combined with ACT against a waiting list control condition as a first test of the effects of treatment. METHODS: Selection took place with a computerized screening interview and a subsequent semi-structured telephone interview. A total of 80 individuals from the general public were randomized to one of two conditions. The treatment lasted for 8 weeks after which both groups were assessed. We also included a 3 month follow-up. The treatment included interactive elements online and a CD-ROM for mindfulness and acceptance exercises. In addition, written support and feedback was given by a therapist every week. RESULTS: Results at posttreatment showed a large between group effect size on the Beck Depression inventory II d=0.98 (95%CI=0.51-1.44). In the treated group 25% (10/40) reached remission defined as a BDI score ≤ 10 vs. 5% (2/40) in the control group. Results on secondary measures were smaller. While few dropped out from the study (N=2) at posttreatment, the average number of completed modules was M=5.1 out of the seven modules. LIMITATIONS: The study only included a waiting-list comparison and it is not possible to determine which treatment components were the most effective. CONCLUSIONS: We conclude that there is initial evidence that BA with components of ACT can be effective in reducing symptoms of depression.

Therapeutic alliance in guided internet-delivered cognitive behavioural treatment of depression, generalized anxiety disorder and social anxiety disorder.

Guided internet-delivered cognitive behaviour therapy (ICBT) has been found to be effective in several controlled trials, but the mechanisms of change are largely unknown. Therapeutic alliance is a factor that has been studied in many psychotherapy trials, but the role of therapeutic alliance in ICBT is less well known. The present study investigated early alliance ratings in three separate samples. Participants from one sample of depressed individuals (N = 49), one sample of individuals with generalized anxiety disorder (N = 35), and one sample with social anxiety disorder (N = 90) completed the Working Alliance Inventory (WAI) modified for ICBT early in the treatment (weeks 3-4) when they took part in guided ICBT for their conditions. Results showed that alliance ratings were high in all three samples and that the WAI including the subscales of Task, Goal and Bond had high internal consistencies. Overall, correlations between the WAI and residualized change scores on the primary outcome measures were small and not statistically significant. We conclude that even if alliance ratings are in line with face-to-face studies, therapeutic alliance as measured by the WAI is probably less important in ICBT than in regular face-to-face psychotherapy.

Internet administered guided self-help versus individualized e-mail therapy: A randomized trial of two versions of CBT for major depression.

Internet-delivered psychological treatment of major depression has been investigated in several trials, but the role of personalized treatment is less investigated. Studies suggest that guidance is important and that automated computerized programmes without therapist support are less effective. Individualized e-mail therapy for depression has not been studied in a controlled trial. Eighty-eight individuals with major depression were randomized to two different forms of Internet-delivered cognitive behaviour therapy (CBT), or to a waiting-list control group. One form of Internet treatment consisted of guided self-help, with weekly modules and homework assignments. Standard CBT components were presented and brief support was provided during the treatment. The other group received e-mail therapy, which was tailored and did not use the self-help texts i.e., all e-mails were written for the unique patient. Both treatments lasted for 8 weeks. In the guided self-help 93% completed (27/29) and in the e-mail therapy 96% (29/30) completed the posttreatment assessment. Results showed significant symptom reductions in both treatment groups with moderate to large effect sizes. At posttreatment 34.5% of the guided self-help group and 30% of the e-mail therapy group reached the criteria of high-end-state functioning (Beck Depression Inventory score below 9). At six-month follow-up the corresponding figures were 47.4% and 43.3%. Overall, the difference between guided self-help and e-mail therapy was small, but in favour of the latter. These findings indicate that both guided self-help and individualized e-mail therapy can be effective.