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.

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.

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 problems reported by cancer patients with major depression.

OBJECTIVE: To describe the problems reported by people with cancer and major depressive disorder as elicited before starting problem-solving therapy (PST). METHODS: Ninety-eight outpatients, with a variety of cancers who met criteria for major depression, received PST as part of a system of treatment called 'Depression Care for People with Cancer' within a randomized trial. During the first session of PST, each patient was asked to provide an exhaustive list of problems defined as 'anything that was bothering them'. A coding system, based on thematic content, was developed to categorize the problems listed. Each problem was then coded by two raters independently (κ=0.81). The resulting categories were organized into larger conceptual domains using a card-sorting task. RESULTS: Thirty-six problem categories were generated which were in turn organized into 11 larger conceptual domains. Patients reported problems in a mean of 9.2 different categories (range 3-21) and 5.7 domains (range 2-9). The most common problem categories were 'concerns about other people's well-being' (65%), 'problems in interpersonal relations' (61%), 'loss of interest' (56%), 'low mood' (55%), and 'cancer recurrence or relapse' (54%). CONCLUSIONS: People with cancer and major depression report a wide variety of problems that include, but go beyond concerns about, both cancer and depression. The large number of problems related to concerns about other people's well-being and difficulties in interpersonal relationships, stresses the importance of these topics to patients and should be given more weight in the assessment and management of depressed cancer patients.

Problem-solving therapy for adult depression: An updated meta-analysis.

BACKGROUND: Problem-solving therapy (PST) is one of the best examined types of psychotherapy for adult depression. No recent meta-analysis has examined the effects of PST compared to control groups or to other treatments. We wanted to verify whether PST is effective, whether effects are comparable to those of other treatments, and whether we could identify the possible sources of high heterogeneity that was found in earlier meta-analyses. METHODS: We conducted systematic searches in bibliographical databases, including PubMed, PsycInfo, Embase and the Cochrane database of randomized trials. RESULTS: We included 30 randomized controlled trials on PST (with 3530 patients), in which PST was compared to control conditions, with other therapies, and with pharmacotherapy. We could compare these 30 trials on PST also with 259 trials on other psychotherapies for adult depression. The effect size of PST versus control groups was g=0.79 (0.57-1.01) with very high heterogeneity (I2=84; 95% CI: 77-88). The effect size from the 9 studies with low risk of bias was g=0.34 (95% CI: 0.22-0.46) with low heterogeneity (I2=32; 95% CI: 0-68), which is comparable to the effects of other psychotherapies. PST was a little more effective than other therapies in direct comparisons, but that may be explained by the considerable number of studies with researcher allegiance towards PST. In meta-regression analyses of all controlled studies, no significant difference between PST and other therapies was found. CONCLUSION: PST is probably an effective treatment for depression, with effect sizes that are small, but comparable to those found for other psychological treatments of depression.

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.

A randomized controlled trial on the role of support in Internet-based problem solving therapy for depression and anxiety.

Internet-based interventions can be effective treatments for anxiety and depression. Meta-analytic evidence suggests that they should be delivered with human support to reach optimal effects. These findings have not consistently been replicated in direct comparisons of supported and unsupported interventions, however. This study examined the role of support in Internet-based problem solving treatment (PST) for symptoms of anxiety and/or depression. Adults with mild to moderate symptoms of anxiety and/or depression were recruited from the general population and randomized to: (1) PST without support (n = 107), (2) PST with support on request (n = 108), (3) PST with weekly support (n = 106), (4) no Internet-based intervention but non-specific chat or email (n = 110), or (5) waitlist control (WLC; n = 106). Primary outcomes were symptoms of anxiety (HADS) and depression (CES-D) measured at baseline and 6 weeks later. Analyses were first based on the intention-to-treat principle (ITT) and repeated with intervention completers. Only participants who received PST with weekly support improved significantly more than WLC for depressive symptoms. Results for anxiety were less robust but in favor of the weekly support condition. The results underscore the importance of structural support in Internet-based interventions for depression and anxiety.

Short-term effectiveness of an online behavioral training in migraine self-management: a randomized controlled trial.

Behavioral training (BT) is recommended as a supplementary preventive treatment for migraine. Online interventions have been successful in promoting health behavior change, the evidence for online BT in migraine is limited, however. This randomized controlled trial aimed to determine the post-treatment effectiveness of online BT (n = 195) compared to a waitlist control group (WLC; n = 173) on migraine attack frequency (primary outcome), headache self-efficacy and locus of control (secondary outcomes). BT aims to counteract attacks in the prodromal stage through early detection of prodromal features and self-management via physical relaxation and cognitive behavioral regulation, and was offered with minimal e-mail support in eight online lessons. Results showed that 120 (62%) participants completed BT. A decrease of 20-25% in migraine attack frequency was found in both conditions without a between-group difference (ES = 0.02, p = .71). BT participants improved more than WLC participants on migraine related self-efficacy (ES = 0.86, p < .001), developed more internal (ES = 0.57, p < .001), and less external control (ES = 0.78, p < .001). To conclude, results at post-training did not corroborate that improvements in migraine attack frequency were due to online BT, the waitlist control group improved accordingly. However, positive effects of BT on self-efficacy and locus of control were established. We have to await the long term effects to see if improvements in psychological variables translate to a reduction in migraine headache.

Patient and general practitioner preferences for the treatment of depression in patients with cancer: how, who, and where?

OBJECTIVE: The objective of this study was to determine and compare patient and general practitioner (GP) preferences for the treatment of depression in patients with cancer. METHODS: A treatment preference questionnaire was completed by 100 patients who had been diagnosed with both cancer and major depressive disorder and by 86 GPs who had had experience of at least 1 patient with cancer and depression. Participants were asked to rank options for how depression should be treated, who should deliver the treatment, and where treatment should occur. RESULTS: The top three preferences of patients and GPs for how depression should be treated differed (P<.001). Patients preferred talking treatment alone, whereas GPs preferred a combination of drug and talking treatment. Both patients and GPs preferred treatment to be given by the GP, with older patients having a stronger preference for this. Counselors and cancer nurses were also popular preferences; mental heath professionals were unpopular. The preferred place of treatment was primary care for both patients and GPs, although many patients preferred treatment in the cancer center. CONCLUSION: Effective and acceptable services for depressed cancer patients need to take patients and GP preferences into account. A model of service that allows a choice of initial treatment modality and collaborative care between primary care and cancer center nurse would meet this requirement.