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.

The Clinical Effectiveness of Blended Cognitive Behavioral Therapy Compared With Face-to-Face Cognitive Behavioral Therapy for Adult Depression: Randomized Controlled Noninferiority Trial.

BACKGROUND: Internet-based cognitive behavioral therapy (iCBT) has been demonstrated to be cost- and clinically effective. There is a need, however, for increased therapist contact for some patient groups. Combining iCBT with traditional face-to-face (FtF) consultations in a blended format may produce a new treatment format (B-CBT) with multiple benefits from both traditional CBT and iCBT, such as individual adaptation, lower costs than traditional therapy, wide geographical and temporal availability, and possibly lower threshold to implementation. OBJECTIVE: The primary aim of this study is to compare directly the clinical effectiveness of B-CBT with FtF-CBT for adult major depressive disorder. METHODS: A 2-arm randomized controlled noninferiority trial compared B-CBT for adult depression with treatment as usual (TAU). The trial was researcher blinded (unblinded for participants and clinicians). B-CBT comprised 6 sessions of FtF-CBT alternated with 6-8 web-based CBT self-help modules. TAU comprised 12 sessions of FtF-CBT. All participants were aged 18 or older and met the diagnostic criteria for major depressive disorder and were recruited via a national iCBT clinic. The primary outcome was change in depression severity on the 9-item Patient Health Questionnaire (PHQ-9). Secondary analyses included client satisfaction (8-item Client Satisfaction Questionnaire [CSQ-8]), patient expectancy (Credibility and Expectancy Questionnaire [CEQ]), and working (Working Alliance Inventory [WAI] and Technical Alliance Inventory [TAI]). The primary outcome was analyzed by a mixed effects model including all available data from baseline, weekly measures, 3-, 6, and 12-month follow-up. RESULTS: A total of 76 individuals were randomized, with 38 allocated to each treatment group. Age ranged from 18 to 71 years (SD 13.96) with 56 (74%) females. Attrition rate was 20% (n=15), which was less in the FtF-CBT group (n=6, 16%) than in the B-CBT group (n=9, 24%). As many as 53 (70%) completed 9 or more sessions almost equally distributed between the groups (nFtF-CBT=27, 71%; nB-CBT=26, 68%). PHQ-9 reduced 11.38 points in the FtF-CBT group and 8.10 in the B-CBT group. At 6 months, the mean difference was a mere 0.17 points. The primary analyses confirmed large and significant within-group reductions in both groups (FtF-CBT: ß=-.03; standard error [SE] 0.00; P<.001 and B-CBT: ß=-.02; SE 0.00; P<.001). A small but significant interaction effect was observed between groups (ß=.01; SE 0.00; P=.03). Employment status influenced the outcome differently between groups, where the B-CBT group was seen to profit more from not being full-time employed than the FtF group. CONCLUSIONS: With large within-group effects in both treatment arms, the study demonstrated feasibility of B-CBT in Denmark. At 6 months' follow-up, there appeared to be no difference between the 2 treatment formats, with a small but nonsignificant difference at 12 months. The study seems to demonstrate that B-CBT is capable of producing treatment effects that are close to FtF-CBT and that completion rates and satisfaction rates were comparable between groups. However, the study was limited by small sample size and should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov NCT02796573; https://clinicaltrials.gov/ct2/show/NCT02796573. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-016-1140-y.

Effect of Sleep Disturbance Symptoms on Treatment Outcome in Blended Cognitive Behavioral Therapy for Depression (E-COMPARED Study): Secondary Analysis.

BACKGROUND: Sleep disturbance symptoms are common in major depressive disorder (MDD) and have been found to hamper the treatment effect of conventional face-to-face psychological treatments such as cognitive behavioral therapy. To increase the dissemination of evidence-based treatment, blended cognitive behavioral therapy (bCBT) consisting of web-based and face-to-face treatment is on the rise for patients with MDD. To date, no study has examined whether sleep disturbance symptoms have an impact on bCBT treatment outcomes and whether it affects bCBT and treatment-as-usual (TAU) equally. OBJECTIVE: The objectives of this study are to investigate whether baseline sleep disturbance symptoms have an impact on treatment outcomes independent of treatment modality and whether sleep disturbance symptoms impact bCBT and TAU in routine care equally. METHODS: The study was based on data from the E-COMPARED (European Comparative Effectiveness Research on Blended Depression Treatment Versus Treatment-as-Usual) study, a 2-arm, multisite, parallel randomized controlled, noninferiority trial. A total of 943 outpatients with MDD were randomized to either bCBT (476/943, 50.5%) or TAU consisting of routine clinical MDD treatment (467/943, 49.5%). The primary outcome of this study was the change in depression symptom severity at the 12-month follow-up. The secondary outcomes were the change in depression symptom severity at the 3- and 6-month follow-up and MDD diagnoses at the 12-month follow-up, assessed using the Patient Health Questionnaire-9 and Mini-International Neuropsychiatric Interview, respectively. Mixed effects models were used to examine the association of sleep disturbance symptoms with treatment outcome and treatment modality over time. RESULTS: Of the 943 patients recruited for the study, 558 (59.2%) completed the 12-month follow-up assessment. In the total sample, baseline sleep disturbance symptoms did not significantly affect change in depressive symptom severity at the 12-month follow-up (ß=.16, 95% CI -0.04 to 0.36). However, baseline sleep disturbance symptoms were negatively associated with treatment outcome for bCBT (ß=.49, 95% CI 0.22-0.76) but not for TAU (ß=-.23, 95% CI -0.50 to 0.05) at the 12-month follow-up, even when adjusting for baseline depression symptom severity. The same result was seen for the effect of sleep disturbance symptoms on the presence of depression measured with Mini-International Neuropsychiatric Interview at the 12-month follow-up. However, for both treatment formats, baseline sleep disturbance symptoms were not associated with depression symptom severity at either the 3- (ß=.06, 95% CI -0.11 to 0.23) or 6-month (ß=.09, 95% CI -0.10 to 0.28) follow-up. CONCLUSIONS: Baseline sleep disturbance symptoms may have a negative impact on long-term treatment outcomes in bCBT for MDD. This effect was not observed for TAU. These findings suggest that special attention to sleep disturbance symptoms might be warranted when MDD is treated with bCBT. Future studies should investigate the effect of implementing modules specifically targeting sleep disturbance symptoms in bCBT for MDD to improve long-term prognosis.

Evaluating a Hybrid Web-Based Training Program for Panic Disorder and Agoraphobia: Randomized Controlled Trial.

BACKGROUND: Previous studies provide evidence for the effectiveness of web-based interventions for panic disorder with and without agoraphobia. Smartphone-based technologies hold significant potential for further enhancing the accessibility and efficacy of such interventions. OBJECTIVE: This randomized controlled trial aims to evaluate the efficacy of a guided, hybrid web-based training program based on cognitive behavioral therapy for adults with symptoms of panic disorder. METHODS: Participants (N=92) with total scores in the Panic and Agoraphobia Scale ranging from 9 to 28 were recruited from the general population and allocated either to a hybrid intervention (GET.ON Panic) or to a wait-list control group. The primary outcome was the reduction in panic symptoms, as self-assessed using a web-based version of the Panic and Agoraphobia Scale. RESULTS: Analysis of covariance-based intention-to-treat analyses revealed a significantly stronger decrease in panic symptoms posttreatment (F=9.77; P=.002; Cohen d=0.66; 95% CI 0.24-1.08) in the intervention group than in the wait-list control group. Comparisons between groups of the follow-up measures at 3 and 6 months yielded even stronger effects (3-month follow-up: F=17.40, P<.001, Cohen d=0.89, 95% CI 0.46-1.31; 6-month follow-up: F=14.63, P<.001, Cohen d=0.81, 95% CI 0.38-1.24). CONCLUSIONS: Hybrid web-based training programs may help reduce the symptoms of panic disorder and hence play an important role in improving health care for patients with this debilitating disorder. TRIAL REGISTRATION: German Clinical Trial Register DRKS00005223; https://tinyurl.com/f4zt5ran. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1745-6215-15-427.

Effectiveness and Moderators of an Internet-Based Mobile-Supported Stress Management Intervention as a Universal Prevention Approach: Randomized Controlled Trial.

BACKGROUND: Emerging evidence indicates the effectiveness of internet-based mobile-supported stress management interventions (iSMIs) in highly stressed employees. It is yet unclear, however, whether iSMIs are also effective without a preselection process in a universal prevention approach, which more closely resembles routine occupational health care. Moreover, evidence for whom iSMIs might be suitable and for whom not is scarce. OBJECTIVE: The aim of this study was to evaluate the iSMI GET.ON Stress in a universal prevention approach without baseline inclusion criteria and to examine the moderators of the intervention effects. METHODS: A total of 396 employees were randomly assigned to the intervention group or the 6-month waiting list control group. The iSMI consisted of 7 sessions and 1 booster session and offered no therapeutic guidance. Self-report data were assessed at baseline, 7 weeks, and at 6 months following randomization. The primary outcome was perceived stress. Several a priori defined moderators were explored as potential effect modifiers. RESULTS: Participants in the intervention group reported significantly lower perceived stress at posttreatment (d=0.71, 95% CI 0.51-0.91) and at 6-month follow-up (d=0.61, 95% CI 0.41-0.81) compared to those in the waiting list control group. Significant differences with medium-to-large effect sizes were found for all mental health and most work-related outcomes. Resilience (at 7 weeks, P=.04; at 6 months, P=.01), agreeableness (at 7 weeks, P=.01), psychological strain (at 6 months, P=.04), and self-regulation (at 6 months, P=.04) moderated the intervention effects. CONCLUSIONS: This study indicates that iSMIs can be effective in a broad range of employees with no need for preselection to achieve substantial effects. The subgroups that might not profit had extreme values on the respective measures and represented only a very small proportion of the investigated sample, thereby indicating the broad applicability of GET.ON Stress. TRIAL REGISTRATION: German Clinical Trials Register DRKS00005699; https://www.drks.de/DRKS00005699.

Internet-Delivered Cognitive Behavioral Therapy for Anxiety Disorders in Open Community Versus Clinical Service Recruitment: Meta-Analysis.

BACKGROUND: Ample studies have shown the effectiveness of internet-delivered cognitive behavioral therapy (iCBT) for anxiety disorders. These studies recruited their participants mainly from the community and, to a lesser extent, from within routine care services. Little is known about whether different recruitment strategies lead to different treatment effects. OBJECTIVE: This meta-analysis compared clinical results obtained in trials with recruitment from the community versus results obtained in trials with clinical service recruitment and explored factors that may mediate differences in treatment outcome. METHODS: We included randomized controlled trials in which the clinical effects of iCBT for anxiety disorders were compared with a control condition (waitlist controls or face-to-face cognitive behavioral therapy). We classified trials as open recruitment trials (recruitment from the community) or clinical service recruitment trials (recruitment through outpatient clinics). Pooled effect sizes based on measures examining anxiety symptoms, depressive symptoms, and quality of life were computed for each type of trial. Subgroup analyses examined whether clinical results from open recruitment trials differed from those obtained in clinical service recruitment trials. Additional analyses explored which demographic, clinical, and treatment-related factors contributed to differences in effect sizes of open recruitment versus clinical service recruitment trials. RESULTS: We included 42 studies with 53 comparisons (43 open recruitment comparisons and 10 clinical recruitment comparisons). Analyses of anxiety measures revealed, first, that iCBT open recruitment studies with waitlist control comparators showed a significantly higher effect size for decrease in anxiety symptoms than did those with clinical recruitment (Q=10.09; P=.001). This association between recruitment method and effect size was no longer significant in a multivariate metaregression with treatment adherence and exclusion of patients with depressive symptoms entered as additional predictors of effect size. Second, effect size for decrease in anxiety symptoms did not differ significantly between clinical recruitment and open recruitment studies with face-to-face cognitive behavioral therapy comparators. The effects of open recruitment trials and clinical recruitment trials did not differ significantly for the secondary outcomes, compared with face-to-face cognitive behavioral therapy and waitlist controls. CONCLUSIONS: iCBT was effective in samples recruited in clinical practice, but effect sizes were smaller than those found in trials with an open recruitment method for studies with waitlist control comparators. Hence, for patients with anxiety disorders in routine care, the impact of iCBT may not be as positive as for study participants recruited from the community. The difference between open recruitment trials and clinical service recruitment trials might be partly explained by patients' greater therapy adherence in open recruitment trials and the stricter exclusion of patients with severe depressive symptoms in these studies. Since most trials in this meta-analysis applied an open recruitment method, more studies with routine care populations are needed to further validate these findings.

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.

Is self-guided internet-based cognitive behavioural therapy (iCBT) harmful? An individual participant data meta-analysis.

BACKGROUND: Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration. METHODS: Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates. RESULTS: Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates. CONCLUSIONS: Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.

Economic Evaluation of an Internet-Based Preventive Cognitive Therapy With Minimal Therapist Support for Recurrent Depression: Randomized Controlled Trial.

BACKGROUND: Major depressive disorder (MDD) is highly recurrent and has a significant disease burden. Although the effectiveness of internet-based interventions has been established for the treatment of acute MDD, little is known about their cost effectiveness, especially in recurrent MDD. OBJECTIVES: Our aim was to evaluate the cost effectiveness and cost utility of an internet-based relapse prevention program (mobile cognitive therapy, M-CT). METHODS: The economic evaluation was performed alongside a single-blind parallel group randomized controlled trial. Participants were recruited via media, general practitioners, and mental health care institutions. In total, 288 remitted individuals with a history of recurrent depression were eligible, of whom 264 were randomly allocated to M-CT with minimal therapist support added to treatment as usual (TAU) or TAU alone. M-CT comprised 8 online lessons, and participants were advised to complete 1 lesson per week. The economic evaluation was performed from a societal perspective with a 24-month time horizon. The health outcomes were number of depression-free days according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria assessed with the Structured Clinical Interview for DSM-IV axis I disorders by blinded interviewers after 3, 12, and 24 months. Quality-adjusted life years (QALYs) were self-assessed with the three level version of the EuroQol Five Dimensional Questionnaire (EQ-5D-3L). Costs were assessed with the Trimbos and Institute for Medical Technology Assessment Questionnaire on Costs Associated with Psychiatric Illness (TiC-P). Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were displayed to assess the probability that M-CT is cost effective compared to TAU. RESULTS: Mean total costs over 24 months were €8298 (US $9415) for M-CT and €7296 (US $8278) for TAU. No statistically significant differences were found between M-CT and TAU regarding depression-free days and QALYs (P=.37 and P=.92, respectively). The incremental costs were €179 (US $203) per depression-free day and €230,816 (US $261,875) per QALY. The cost-effectiveness acceptability curves suggested that for depression-free days, high investments have to be made to reach an acceptable probability that M-CT is cost effective compared to TAU. Regarding QALYs, considerable investments have to be made but the probability that M-CT is cost effective compared to TAU does not rise above 40%. CONCLUSIONS: The results suggest that adding M-CT to TAU is not effective and cost effective compared to TAU alone. Adherence rates were similar to other studies and therefore do not explain this finding. The participants scarcely booked additional therapist support, resulting in 17.3 minutes of mean total therapist support. More studies are needed to examine the cost effectiveness of internet-based interventions with respect to long-term outcomes and the role and optimal dosage of therapist support. Overall, more research is needed on scalable and cost-effective interventions that can reduce the burden of recurrent MDD. TRIAL REGISTRATION: Netherlands Trial Register NTR2503; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2503 (Archived by WebCite at http://www.webcitation.org/73aBn41r3).

Internet-based vs. face-to-face cognitive behavior therapy for psychiatric and somatic disorders: an updated systematic review and meta-analysis.

During the last two decades, Internet-delivered cognitive behavior therapy (ICBT) has been tested in hundreds of randomized controlled trials, often with promising results. However, the control groups were often waitlisted, care-as-usual or attention control. Hence, little is known about the relative efficacy of ICBT as compared to face-to-face cognitive behavior therapy (CBT). In the present systematic review and meta-analysis, which included 1418 participants, guided ICBT for psychiatric and somatic conditions were directly compared to face-to-face CBT within the same trial. Out of the 2078 articles screened, a total of 20 studies met all inclusion criteria. Results showed a pooled effect size at post-treatment of Hedges g = .05 (95% CI, -.09 to .20), indicating that ICBT and face-to-face treatment produced equivalent overall effects. Study quality did not affect outcomes. While the overall results indicate equivalence, there have been few studies of the individual psychiatric and somatic conditions so far, and for the majority, guided ICBT has not been compared against face-to-face treatment. Thus, more research, preferably with larger sample sizes, is needed to establish the general equivalence of the two treatment formats.

Internet and mobile interventions for depression: Opportunities and challenges.

BACKGROUND: The Internet offers several new ways of developing, implementing, and disseminating evidence-based interventions for depression. METHODS: In this paper, we narratively synthesized the evidence showing that Internet-based therapies are effective in treating depression. RESULTS: In the past decade, a considerable number of psychological treatments have been developed for the treatment of depression and several hundreds of randomized controlled trials have been conducted, showing that these interventions are effective and that there are no major differences in effects between therapies. Several meta-analyses show that Internet-based treatments are also effective in depression. Direct comparisons with face-to-face treatments do not indicate that there are relevant differences between Internet-based and face-to-face treatment formats. The challenge for the near future is to examine how these treatments can be integrated in mental health care. Major opportunities are in preventive services, primary care, specialized mental health care, and in patients with comorbid general medical disorders. New technological innovations through the smartphone, serious gaming, avatars, augmented reality, and virtual reality will give further possibilities to simplify and perhaps increase the effects of treatments. CONCLUSIONS: The Internet offers many possibilities to increase access to evidence-based psychological treatments of depression. New technological may further improve access and, perhaps, the effects of treatments.

The therapist's role in the implementation of internet-based cognitive behavioural therapy for patients with depression: study protocol.

BACKGROUND: Internet-based Cognitive Behavioural Therapy (iCBT) for the treatment of depressive disorders is innovative and promising. Various studies have demonstrated large effect sizes up to 2.27, but implementation in routine practice lags behind. Mental health therapists play a significant role in the uptake of internet-based interventions. Therefore, it is interesting to study factors that influence the therapists in whether they apply internet-based therapy or not. This study, as part of the European implementation project MasterMind, aims to identity the factors that promote or hinder therapists in the use of iCBT in depression care. METHODS/DESIGN: The uptake of iCBT by therapists in routine mental health care practice for the treatment of depression will be evaluated by a mixed method approach, to provide an understanding of the implementation factors (quantitative), and to ascertain the facilitating and hindering factors in the involvement of therapists in the implementation of iCBT (qualitative). The involvement of therapists in the implementation of iCBT is analysed following the RE-AIM framework on the five dimensions Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance. This enables us to evaluate the reach of therapists, the impact of iCBT on depression care, the extent to which therapists adopt iCBT, the extent to which iCBT is delivered as intended, and how iCBT can be maintained over time. DISCUSSION: The results will provide valuable insight into the role of therapists in the implementation of iCBT for depression in secondary mental health care settings. They will result in concrete recommendations for how therapists can be facilitated in implementing and up-scaling iCBT for depression.

Effect of a Web-Based Guided Self-help Intervention for Prevention of Major Depression in Adults With Subthreshold Depression: A Randomized Clinical Trial.

IMPORTANCE: Evidence-based treatments for major depressive disorder (MDD) are not very successful in improving functional and health outcomes. Attention has increasingly been focused on the prevention of MDD. OBJECTIVE: To evaluate the effectiveness of a web-based guided self-help intervention for the prevention of MDD. DESIGN, SETTING, AND PARTICIPANTS: Two-group randomized clinical trial conducted between March 1, 2013, and March 4, 2015. Participants were recruited in Germany from the general population via a large statutory health insurance company (ie, insurance funded by joint employer-employee contributions). Participants included 406 self-selected adults with subthreshold depression (Centre for Epidemiologic Studies Depression Scale score ≥16, no current MDD according to Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition, Text Revision] criteria). INTERVENTIONS: All participants had unrestricted access to usual care (visits to the primary care clinician) and were randomized to either a web-based guided self-help intervention (cognitive-behavioral and problem-solving therapy supported by an online trainer; n = 202) or a web-based psychoeducation program (n = 204). MAIN OUTCOMES AND MEASURES: The primary outcome was time to onset of MDD in the intervention group relative to the control group over a 12-month follow-up period as assessed by blinded diagnostic raters using the telephone-administered Structured Clinical Interview for DSM-IV Axis Disorders at 6- and 12-month follow-up, covering the period to the previous assessment. RESULTS: Among 406 randomized patients (mean age, 45 years; 73.9% women), 335 (82%) completed the telephone follow-up at 12 months. Fifty-five participants (27%) in the intervention group experienced MDD compared with 84 participants (41%) in the control group. Cox regression analyses controlling for baseline depressive symptom severity revealed a hazard ratio of 0.59 (95% CI, 0.42-0.82; P = .002) at 12-month follow-up. The number needed to treat to avoid 1 new case of MDD was 5.9 (95% CI, 3.9-14.6). CONCLUSIONS AND RELEVANCE: Among patients with subthreshold depression, the use of a web-based guided self-help intervention compared with enhanced usual care reduced the incidence of MDD over 12 months. Further research is needed to understand whether the effects are generalizable to both first onset of depression and depression recurrence as well as efficacy without the use of an online trainer. TRIAL REGISTRATION: German Clinical Trial Registry Identifier: DRKS00004709.

Evaluating the efficacy and cost-effectiveness of web-based indicated prevention of major depression: design of a randomised controlled trial.

BACKGROUND: Major depressive disorder (MDD) imposes a considerable disease burden on individuals and societies. Web-based interventions have shown to be effective in reducing depressive symptom severity. However, it is not known whether web-based interventions may also be effective in preventing the onset of MDD. The aim of this study is to evaluate the (cost-) effectiveness of an indicated web-based guided self-help intervention (GET.ON Mood Enhancer Prevention) on the onset of MDD. METHODS/DESIGN: A randomised controlled trial (RCT) will be conducted to compare the (cost-) effectiveness of the GET.ON Mood Enhancer Prevention training with a control condition exclusively receiving online-based psychoeducation on depression. Adults with subthreshold depression (N = 406) will be recruited from the general population and randomised to one of the two conditions. The primary outcome is time to onset of MDD within a 12-months follow-up period. MDD will be assessed according to DSM-IV criteria as assessed by the telephone-administered Structured Clinical Interview for DSM-IV (SCID). Time to onset of MDD will be assessed using life charts. Secondary outcomes include changes on various indicators of depressive symptom severity, anxiety and quality of life from baseline to post-treatment, to a 6-month and a 12-month follow up. Additionally, an economic evaluation using a societal perspective will be conducted to examine the intervention's cost-effectiveness. DISCUSSION: This is one of the first randomised controlled trials that examines the effect of an indicated guided self-help web-based intervention on the incidence of major depression. If shown to be effective, the intervention will contribute to reducing the disease burden due to MDD in the general population. TRIAL REGISTRATION: German Clinical Trial Registration DRKS00004709.

[Internet-based approaches in prevention and treatment of depressive symptoms in adolescents and young adults ]. / Internetbasierte Ansätze in der Prävention und Behandlung von depressiven Beschwerden bei Jugendlichen und jungen Erwachsenen.

Epidemiological findings indicate that up to 18.5 % of the German adolescents suffer from depressive symptoms and that younger adults display the highest risk for relevant symptoms of depression (9.9 %) within the German adult population. Internet-based interventions have been shown to be useful for preventing and treating depression and are more easily disseminated in internet-savvy generations. Available programs are usually based on principles of cognitive behavioural therapy. They differ significantly with regard to target groups, structure, content, degree of guidance provided by online-coaches and evidence for their efficacy. Whereas some studies could not prove the use of the trainings there are others that show large effect sizes (up to d = 0.84) for the reduction of depressive symptoms. In Germany there are some online counseling programs for children and adolescents in (acute) crises available. However, at this point no structured intervention program for the treatment of depression exists.

Web-Based, Human-Guided, or Computer-Guided Transdiagnostic Cognitive Behavioral Therapy in University Students With Anxiety and Depression: Randomized Controlled Trial.

BACKGROUND: Internet-based cognitive behavioral interventions (iCBTs) are efficacious treatments for depression and anxiety. However, it is unknown whether adding human guidance is feasible and beneficial within a large educational setting. OBJECTIVE: This study aims to potentially demonstrate the superiority of 2 variants of a transdiagnostic iCBT program (human-guided and computer-guided iCBT) over care as usual (CAU) in a large sample of university students and the superiority of human-guided iCBT over computer-guided iCBT. METHODS: A total of 801 students with elevated levels of anxiety, depression, or both from a large university in the Netherlands were recruited as participants and randomized to 1 of 3 conditions: human-guided iCBT, computer-guided iCBT, and CAU. The primary outcome measures were depression (Patient Health Questionnaire) and anxiety (Generalized Anxiety Disorder scale). Secondary outcomes included substance use-related problems (Alcohol Use Disorder Identification Test and Drug Abuse Screening Test-10 items). Linear mixed models were used to estimate the effects of time, treatment group, and their interactions (slopes). The primary research question was whether the 3 conditions differed in improvement over 3 time points (baseline, midtreatment, and after treatment) in terms of depression and anxiety symptoms. Results were analyzed according to the intention-to-treat principle using multiple imputation. Patients were followed exploratively from baseline to 6 and 12 months. RESULTS: In both short-term and long-term analyses, the slopes for the 3 conditions did not differ significantly in terms of depression and anxiety, although both web-based interventions were marginally more efficacious than CAU over 6 months (P values between .02 and .03). All groups showed significant improvement over time (P<.001). For the secondary outcomes, only significant improvements over time (across and not between groups) were found for drug use (P<.001). Significant differences were found in terms of adherence, indicating that participants in the human-guided condition did more sessions than those in the computer-guided condition (P=.002). CONCLUSIONS: The transdiagnostic iCBT program offers a practical, feasible, and efficacious alternative to usual care to tackle mental health problems in a large university setting. There is no indication that human guidance should be preferred over technological guidance. The potential preference of human support also depends on the scale of implementation and cost-effectiveness, which need to be addressed in future trials. TRIAL REGISTRATION: International Clinical Trials Registry Platform NL7328/NTR7544; https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON26795.

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.

Effects of a minimal-guided on-line intervention for alcohol misuse in Estonia: a randomized controlled trial.

BACKGROUND AND AIMS: Estonia has one of the highest alcohol-attributable mortality rates within the European Union. The aim of this study was to estimate the efficacy of an on-line self-help intervention to reduce problem drinking at the population level. DESIGN: On-line open randomized controlled trial with an 8-week intervention and an active control group (intervention n = 303, control n = 286). Assessments took place at baseline and at 6 months follow-up. SETTING: On- and offline channels were used for population-based recruitment within a nation-wide prevention campaign in Estonia. PARTICIPANTS: Inclusion criteria were age ≥ 18 years, heavy drinking [Alcohol Use Disorders Identification (AUDIT) test score ≥ 8], literacy in Estonian and at least weekly access to the internet; n = 589 participants were randomized (50% male, 1% other; mean age 37.86 years; 45% with higher level of education). INTERVENTION AND COMPARATOR: The intervention consisted of 10 modules based on principles of cognitive-behavioral therapy and motivational interviewing. The active control group received access to a website with a self-test including personalized normative feedback and information for standard alcohol treatment. MEASUREMENTS: The primary outcome was AUDIT scores at 6 months follow-up adjusted for baseline scores. FINDINGS: Intention-to-treat analyses were applied. Missing data were addressed by using baseline observation carried forward (BOCF) and multiple imputation by chained equations (MI); 175 completed follow-up in the intervention group and 209 in the control group. AUDIT score at follow-up was significantly smaller in the intervention [BOCF mean = 13.91, standard deviation (SD) = 7.61, MI mean = 11.03, SD = 6.55] than control group (BOCF mean = 15.30, SD = 7.31; MI mean = 14.30, SD = 7.21), with a group difference of -1.38 [95% confidence interval (CI) = -2.58, -0.18], P = 0.02 for BOCF and -3.26 (95% CI = -2.01, -4.51), P < 0.001 for MI. CONCLUSIONS: A randomized controlled trial has found that an on-line self-help intervention with minimal guidance was effective at reducing problem drinking in Estonia.

Guided internet-based transdiagnostic individually tailored Cognitive Behavioral Therapy for symptoms of depression and/or anxiety in college students: A randomized controlled trial.

Common mental disorders, such as depression and anxiety, often emerge in college students during the transition into early adulthood. Mental health problems can seriously impact students' functioning, interpersonal relationships, and academic achievement. Actively reaching out to college students with mental health problems and offering them internet-based interventions may be a promising way of providing low-threshold access to evidence-based treatment in colleges. This randomized controlled trial aimed to assess the effectiveness of a guided web-based transdiagnostic individually tailored Cognitive Behavioral Therapy (iCBT) in treating college students with depression and/or anxiety symptoms. Through an online survey that screened college students' mental health, we recruited 100 college students aged ≥18 years who reported mild to moderate depression and/or anxiety symptoms and were attending colleges in the Netherlands. Participants were randomly allocated to guided iCBT (n = 48) or treatment as usual (TAU) control (n = 52). Primary outcomes were symptoms of depression and anxiety measured at post-treatment (7 weeks post-randomization). We also measured all outcomes at 6- and 12-months post-randomization. All analyses were based on the intention-to-treat principle and were repeated using the complete-case sample. We found no evidence of a difference between the effects of guided iCBT and TAU in any of the examined outcomes (i.e., symptoms of depression and anxiety, quality of life, educational achievement, and college dropout) across all time points (p > .05). There was no evidence that effects of iCBT were associated with treatment satisfaction and adherence. More research into transdiagnostic individually tailored iCBT is necessary. Further, future studies should recruit larger samples to investigate possible smaller but clinically relevant effects of internet-based interventions for college students with depression and/or anxiety.