Clinical effectiveness of internet-based cognitive behavioral therapy for insomnia in routine secondary care: results of a randomized controlled trial.

Introduction: Delivering cognitive behavioral therapy for insomnia over the internet bears the advantage of accessibility and uptake to many patients suffering from chronic insomnia. In the current study, we aimed to investigate the effectiveness of internet-based cognitive behavioral therapy for insomnia (iCBT-I) in routine care. Materials and methods: We conducted a two-arm non-blinded randomized controlled trial with care as usual (CAU) as a control condition. Participants were recruited in a specialized outpatient sleep medicine department. Both arms had access to other healthcare resources, and the intervention group had access to the iCBT-I program for 2 months. The primary outcome was insomnia severity, measured by the Insomnia Severity Index (ISI). Secondary outcomes were fatigue severity, daytime sleepiness, affective symptoms, dysfunctional beliefs and attitudes about sleep, sleep locus of control, sleep hygiene, sleep efficiency (SE), sleep onset latency, wake time after sleep onset (WASO), and total sleep time (TST). Linear mixed models for repeated measures were used to analyze the longitudinal data at baseline, post-treatment, and after 3 months of follow-up. The trial was registered at www.clinicaltrials.gov (NCT04300218 21.04.2020). Results: The results showed a significant time*group interaction effect (p = 0.001) at post-treatment with between-group effect size (d = 0.51), indicating that the ISI decreased by a score of 3.8-fold in the iCBT-I group than in the CAU group. There was no significant difference in ISI between groups at follow-up. Regarding secondary outcomes, dysfunctional beliefs about sleep, SE, and WASO decreased significantly during treatment in the intervention group with between-group effect sizes d = 0.35, d = -0.51, and d = 0.47, respectively. At the follow-up, between-group effects on DBAS and SE remained significant: d = 0.36 and d = -0.63, respectively. For TST, we observed a significant time*group effect of d = -0.38 only after follow-up. Conclusion: Our findings suggest that iCBT-I has a significant effect on insomnia severity at post-treatment compared to CAU. iCBT-I further improved dysfunctional beliefs about sleep and improved subjective sleep characteristics, such as SE, WASO, and TST during 3 months after treatment. Clinical trial registration: www.clinicaltrials.gov, identifier (NCT04300218).

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.

Efficacy of an Internet- and Mobile-Based Intervention for Subclinical Anxiety and Depression (ICare Prevent) with Two Guidance Formats: Results from a Three-Armed Randomized Controlled Trial.

INTRODUCTION: Limited research exists on intervention efficacy for comorbid subclinical anxiety and depressive disorders, despite their common co-occurrence. Internet- and mobile-based interventions (IMIs) are promising to reach individuals facing subclinical symptoms. OBJECTIVE: This study aimed to evaluate the efficacy of a transdiagnostic and self-tailored IMI in reducing subclinical anxiety and depressive symptom severity with either individualized (IG-IMI) or automated (AG-IMI) guidance compared to a waitlist control group with care-as-usual access (WLC). METHODS: Participants included 566 adults with subclinical anxiety (GAD-7 ≥ 5) and/or depressive (CES-D ≥16) symptoms, who did not meet criteria for a full-syndrome depressive or anxiety disorder. In a three-arm randomized clinical trial, participants were randomized to a cognitive behavioral 7-session IMI plus booster session with IG-IMI (n = 186) or AG-IMI (n = 189) or WLC (n = 191). Primary outcomes included observer-rated anxiety (HAM-A) and depressive (QIDS) symptom severity 8 weeks after randomization assessed by blinded raters via telephone. Follow-up outcomes at 6 and 12 months are reported. RESULTS: Symptom severity was significantly lower with small to medium effects in IG-IMI (anxiety: d = 0.45, depression: d = 0.43) and AG-IMI (anxiety: d = 0.31, depression: d = 0.32) compared to WLC. No significant differences emerged between guidance formats in primary outcomes. There was a significant effect in HAM-A after 6 months favoring AG-IMI. On average, participants completed 85.38% of IG-IMI and 77.38% of AG-IMI. CONCLUSIONS: A transdiagnostic, self-tailored IMI can reduce subclinical anxiety and depressive symptom severity, but 12-month long-term effects were absent. Automated guidance holds promise for enhancing the scalability of IMIs in broad prevention initiatives.

Efficacy of an Internet-based self-help intervention with human guidance or automated messages to alleviate loneliness: a three-armed randomized controlled trial.

Loneliness is a prevalent and stigmatized phenomenon associated with adverse (mental) health outcomes. However, evidence-based interventions to alleviate loneliness are scarce. This randomized controlled trial (ClinicalTrials.gov-ID: NCT04655196) evaluated the efficacy of an internet-based cognitive behavioral self-help intervention (ICBT) to reduce loneliness by comparing two intervention groups with guidance or automated messages against a waitlist control group. Adults (N = 243) suffering from loneliness were recruited from the general public and then randomly assigned (2:2:1) to a 10-week ICBT with human guidance (GU) or automated messages (AM) or to a waitlist control group (WL). Loneliness, assessed with the UCLA-9, was the primary outcome. Outcomes were assessed at baseline and 10 weeks (post) and analyzed using mixed-effects models. The pooled intervention conditions resulted in lower loneliness scores at post-assessment than the WL (Cohen's d = 0.57, 95% CI [0.25; 0.89]) and reduced depressive symptoms, social anxiety, social avoidance behavior, and rejection sensitivity (d = 0.32-0.52). The GU group had lower loneliness scores at post-assessment than the AM group (d = 0.42, 95% CI [0.13; 0.70]). ICBT effectively alleviated loneliness, and guidance increased the reduction in loneliness compared to automated messages. Alleviating loneliness with ICBT further seems to reduce the overall burden of psychopathological symptoms.

Postfabrication Tuning of Circular Bragg Resonators for Enhanced Emitter-Cavity Coupling.

Solid-state quantum emitters embedded in circular Bragg resonators are attractive due to their ability to emit quantum light with high brightness and low multiphoton probability. As for any emitter-microcavity system, fabrication imperfections limit the spatial and spectral overlap of the emitter with the cavity mode, thus limiting their coupling strength. Here, we show that an initial spectral mismatch can be corrected after device fabrication by repeated wet chemical etching steps. We demonstrate an ∼16 nm wavelength tuning for optical modes in AlGaAs resonators on oxide, leading to a 4-fold Purcell enhancement of the emission of single embedded GaAs quantum dots. Numerical calculations reproduce the observations and suggest that the achievable performance of the resonator is only marginally affected in the explored tuning range. We expect the method to be applicable also to circular Bragg resonators based on other material platforms, thus increasing the device yield of cavity-enhanced solid-state quantum emitters.

Predictors and moderators of outcome of ICBT for loneliness with guidance or automated messages - A secondary analysis of a randomized controlled trial.

Internet-based cognitive behavioral therapy (ICBT) is promising in alleviating loneliness in adults. Identifying individuals who benefit from ICBT for loneliness is pivotal to offering this intervention in a more targeted way and improving the intervention for those who do not benefit. This secondary analysis of a randomized controlled trial (RCT) aimed to identify predictors and moderators of outcome of an ICBT with guidance or automated messages for loneliness. In the RCT, 243 participants suffering from loneliness were randomly assigned to an ICBT with guidance (n = 98), automated messages (n = 97), or a waitlist-control condition (n = 48). In total, 180 participants completed the post-assessment (i.e., 10 weeks post-randomization). Outcomes were treatment outcome assessed with the UCLA-9 Loneliness Scale at post-assessment and treatment response, i.e., reliable improvement on the UCLA-9 from pre- to post. The relationship between a wide range of patient characteristics (grouped into socio-demographic, clinical, loneliness-specific, and treatment-related variables) and outcome was analyzed using multiple linear and logistic regressions. Feeling less burdened by loneliness resulted in higher odds of reliable improvement in guided ICBT compared to the waitlist-control condition. No treatment outcome or response moderators were identified for ICBT with automated messages compared to the waitlist-control group. Across active intervention groups, loneliness at baseline, age and fit between the tasks and goals of the intervention and participants' need predicted treatment outcome. Predictors of treatment response for ICBT with guidance and automated messages were not identified, and no variables differentially predicted the effects of ICBT with guidance or automated messages on the outcomes. In conclusion, individuals less burdened by their feelings of loneliness benefited more from guided ICBT. Lower baseline loneliness scores, younger age, and a better match between tasks and goals of the intervention and participants' needs also predicted a more favorable treatment outcome for both ICBT with guidance and automated messages.

Prognostic Risk Factors in Randomized Clinical Trials of Face-to-Face and Internet-Based Psychotherapy for Depression: A Systematic Review and Meta-Regression Analysis.

Importance: Variables such as severe symptoms, comorbidity, and sociodemographic characteristics (eg, low educational attainment or unemployment) are associated with a poorer prognosis in adults treated for depressive symptoms. The exclusion of patients with a poor prognosis from RCTs is negatively associated with the generalizability of research findings. Objective: To compare the prognostic risk factors (PRFs) in patient samples of RCTs of face-to-face therapy (FTF) and internet-based therapy (IBT) for depression. Data Sources: PsycINFO, Cochrane CENTRAL, and reference lists of published meta-analyses were searched from January 1, 2000, to December 31, 2021. Study Selection: RCTs that compared FTF (individual or group therapy) and IBT (guided or self-guided interventions) against a control (waitlist or treatment as usual) in adults with symptoms of depression were included. Data Extraction and Synthesis: Data were extracted by 2 independent observers. The Cochrane revised risk-of-bias tool was used to assess the risk of bias. The study was preregistered with OSF Registries and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The primary outcome was the standardized mean difference (Hedges g effect size) in depressive symptoms at treatment termination (assessed with standard patient self-report questionnaires), with a positive standardized mean difference indicating larger improvements in the intervention compared with those in the control group. Meta-regression analyses were adjusted for the type of control group. Three preregistered and 2 exploratory sensitivity analyses were conducted. A prognostic risk index (PROG) was created that calculated the sum of 12 predefined individual indicators, with scores ranging from 0 to 12 and higher scores indicating that a sample comprised patients with poorer prognoses. Results: This systematic review and meta-regression analysis identified 105 eligible RCTs that comprised 18 363 patients. In total, 48 studies (46%) examined FTF, and 57 studies (54%) examined IBT. The PROG was significantly higher in the RCTs of FTF than in the RCTs of IBT (FTF: mean [SD], 3.55 [1.75]; median [IQR], 3.5 [2.0-4.5]; IBT: mean [SD], 2.27 [1.66]; median [IQR], 2.0 [1.0-3.5]; z = -3.68, P < .001; Hedges g = 0.75; 95% CI, 0.36-1.15). A random-effects meta-regression analysis found no association of the PROG with the effect size. Sensitivity analyses with outliers excluded and accounting for risk of bias or small-study effects yielded mixed results on the association between the PROG and effect size. Conclusions and Relevance: The findings of this systematic review and meta-regression analysis suggest that samples of RCTs of FTF vs IBT differ with regard to PRFs. These findings have implications for the generalizability of the current evidence on IBT for depression. More RCTs of internet-based interventions with clinically representative samples are needed, and the reporting of PRFs must be improved.

Using machine learning algorithms to predict the effects of change processes in psychotherapy: Toward process-level treatment personalization.

This study aimed to develop and test algorithms to determine the individual relevance of two psychotherapeutic change processes (i.e., mastery and clarification) for outcome prediction. We measured process and outcome variables in a naturalistic outpatient sample treated with an integrative treatment for a variety of diagnoses (n = 608) during the first 10 sessions. We estimated individual within-patient effects of each therapist-evaluated process of change on patient-evaluated subsequent outcomes on a session-by-session basis. Using patients' baseline characteristics, we trained machine learning algorithms on a randomly selected subsample (n = 407) to predict the effects of patients' process variables on outcome. We subsequently tested the predictive capacity of the best algorithm for each process on a holdout subsample (n = 201). We found significant within-patient effects of therapist perceived mastery and clarification on subsequent outcome. In the holdout subsample, the best-performing algorithms resulted in significant but small-to-medium correlations between the predicted and observed relevance of therapist perceived mastery (r = .18) and clarification (r = .16). Using the algorithms to create criteria for individual recommendations, in the holdout sample, we identified patients for whom mastery (14%) or clarification (18%) were indicated. In the mastery-indicated group, a greater focus on mastery was moderately associated with better outcome (r = .33, d = .70), while in the clarification-indicated group, the focus was not related to outcome (r = -.05, d = .10). Results support the feasibility of performing individual predictions regarding mastery process relevance that can be useful for therapist feedback and treatment recommendations. However, results will need to be replicated with prospective experimental designs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Blending an internet-based emotion regulation intervention with face-to-face psychotherapy: Findings from a pilot randomized controlled trial.

Background: Transdiagnostic interventions targeting shared mechanisms may improve treatment of mental health disorders. One way of providing such interventions is through blended treatment. This study examined the addition of an internet-based emotion regulation intervention to face-to-face psychotherapy in an outpatient setting. Methods: In a pilot randomized controlled trial, 70 patients with a range of diagnoses were assigned to an internet-based program targeting emotion regulation + treatment as usual (face-to-face psychotherapy; TAU) (n = 35) or TAU (n = 35). Assessments occurred at baseline, after six, and after 12 weeks and included measures of symptom severity, emotion regulation, and various intervention feasibility parameters. Results: ITT-analyses revealed no significant group-by-time interaction for the primary and almost all secondary outcomes. Descriptively, between-group effect sizes were in favor of the intervention group for almost all outcomes. Sensitivity analysis with patients who completed a minimum of three modules of the internet-based program showed a significant group-by-time interaction for the Difficulties in Emotion Regulation Scale in favor of the intervention group. The internet-based intervention showed good satisfaction ratings, user experience and usability. Findings from therapist measures complemented patient measures. Conclusion: Preliminary results show that an internet-based emotion regulation intervention added to psychotherapy may not reduce symptom severity compared to psychotherapy alone. The intervention was rated positively by patients and therapists regarding several parameters, but certain features still need to be improved. An RCT powered to detect small between-group effect-sizes is necessary to consolidate findings.

Human contact in internet-based interventions for depression: A pre-registered replication and meta-analysis of randomized trials.

Introduction: Internet-based self-help interventions have shown to be effective in the treatment of depression. Several meta-analyses indicated that human contact has a crucial impact on adherence and outcome. While most research focused on the role of guidance during interventions, a review by Andersson and Johansson (2012) suggested that contact before the intervention too may play an important role. Objective: We investigated the impact of the degree of contact in internet-based interventions (IBIs) for depression on outcome in adults suffering from elevated symptoms of depression. Methods: We conducted a preregistered meta-analysis (www.osf.io/4mzyd) and included trials comparing IBIs for depression against control conditions (treatment as usual [TAU] or waiting list [WL]) in patients with symptoms of unipolar depression searching the databases PsycINFO and Cochrane's Central Register of Controlled Trials (CENTRAL) limited to entries from EMBASE and PubMed. Following Andersson and Johansson (2012), contact before an intervention was defined as having had a diagnostic interview before the IBI, and contact during intervention was defined as having received guidance during the IBI. IBIs were grouped as providing (0) no contact, (1) contact before the IBI, (2) contact during the IBI, or (3) contact both before and during the IBI. The primary outcome was standardized mean difference (SMD) of the IBI and control in depressive symptoms at treatment termination. Secondary outcomes were study dropout and adherence to the IBI. Results: We included 56 eligible trials that randomized 13,335 patients to 75 internet-based intervention conditions and control groups (TAU in 23 trials, WL in 33 trials). In total, 44 trials (78.57 %) were judged to show some concerns or a high risk of bias. Overall heterogeneity was high regarding the primary outcome (I2s < 66 %) and even higher for secondary outcomes (I2s < 91 %). Degree of contact was a robust predictor of outcome and adherence in all pre-registered and exploratory analyses. We found the effect of the IBI to increase with higher degree of contact. However, in pair-wise contrasts, only IBIs offering both contact before and during the intervention (SMD = 0.573, 95 % CI: 0.437, 0.709) significantly outperformed interventions offering no contact (SMD = 0.224, 95 % CI: 0.090, 0.340). Conclusions: The results suggest that contact before and during an intervention increases the effects of IBIs. The combination of contact before and during the intervention seems to a pivotal role regarding adherence as well as treatment outcome for patients suffering from depression.

Guided Internet-Based Cognitive Behavioral Therapy for Insomnia: Prognostic and Treatment-Predictive Factors.

Understanding which factors predict the outcome of internet-based cognitive behavioral therapy for insomnia (iCBT-I) may help to tailor this intervention to the patient's needs. We have conducted a secondary analysis of a randomized, controlled trial comparing a multicomponent iCBT-I (MCT) and an online sleep restriction therapy (SRT) for 83 chronic insomnia patients. The difference in the Insomnia Severity Index from pre- to post-treatment and from pre-treatment to follow-up at 6 months after treatment was the dependent variable. Prognostic and treatment-predictive factors assessed at baseline were analyzed with multiple linear regression. The shorter duration of insomnia, female gender, high health-related quality of life, and the higher total number of clicks had prognostic value for a better outcome. Other factors were found to be prognostic for outcome at the follow-up assessment: treatment with benzodiazepines, sleep quality, and personal significance of sleep problems. A high level of dysfunctional beliefs and attitudes about sleep (DBAS) was a moderator for better effects in the MCT at post-treatment assessment. Various prognostic factors (e.g., duration of insomnia, gender, or quality of life) may influence the success of treatment. The DBAS scale may be recommended to select patients for MCT rather than SRT.

The impact of integrating emotion focused components into psychological therapy: A randomized controlled trial.

OBJECTIVES: This paper presents a randomized controlled trial on assimilative integration, which is aimed at integrating elements from other orientations within one approach to enrich its conceptual and practical repertoire. Elements from Emotion-Focused Therapy (EFT) were integrated into a form of cognitive behavior therapy: Psychological Therapy (PT). In one treatment condition, EFT was added to PT (+EFT) with the intent to enhance therapists' working with emotions. In the other condition, concepts and interventions based on the socialpsychological self-regulation approach were added to PT (+SR). Our assumption was that the +EFT would lead to greater and deeper change, particularly in the follow-up assessments. METHOD: Patients (n = 104) with anxiety, depression, or adjustment disorders were randomized to the two conditions and treated by 38 therapists who self-selected between the conditions. Primary outcome was symptom severity at 12-month follow-up; secondary outcomes included several measures such as interpersonal problems and quality of life. Variables were assessed at baseline, after 8 and 16 sessions, at posttreatment, and at 6- and 12-month follow-up. RESULTS: Contrary to our hypothesis, no significant between-group effects were found. CONCLUSION: The findings first suggest the difficulty of topping an already very effective approach to psychotherapy. Alternative interpretations were that the EFT training, while corresponding to regular practice in AI, was not sufficient to make a difference in outcome, or that while profiting from the enhancement of abilities for working with emotions, this was outbalanced by negative effects of difficulties related to the implementation of the new elements.

Working alliance and adherence mediate the effect of guidance in a web-based program for participants with mild to moderate depressive symptoms: A secondary mediation analysis.

Guided web-based self-help programs for individuals with depressive symptoms have shown to be more efficacious than unguided programs. However, research has paid little attention to why guided interventions are superior. The present study investigated whether working alliance and adherence to the program mediated the effect of guidance on depressive symptom outcome. The study is a secondary analysis of a randomized factorial trial. In the trial, 302 adults with mild to moderate depressive symptoms (Patient Health Questionnaire-9 score: 5-14) were randomized to either a guided or an unguided group. All participants received access to a web-based self-help program based on problem-solving therapy. Working alliance with the treatment providers was assessed using an adapted version of the Working Alliance Inventory for Guided Internet Interventions two weeks (early-treatment) and eight weeks (post-treatment) after pre-treatment. The primary outcome was depressive symptoms at post-treatment. The total working alliance score was significantly higher for guided participants compared to unguided participants (at early-treatment: t 248.6 = -3.36, p < .001, d = 0.42, at post-treatment: t 194.9 = -4.77, p < .001, d = 0.66). The total working alliance score correlated significantly with the change in depressive symptoms for guided (rs = 0.16, 0.34) and unguided participants (rs = 0.26, 0.23). The WAI-I total score statistically mediated the relationship between guidance and outcome (at early-treatment: B = -0.028, at post-treatment: B = -0.053). Furthermore, the subscale tasks (at post-treatment: B = -0.051), the subscale goals (at early-treatment: B = -0.031 and at post-treatment: B = -0.052), and adherence to the program (B = -0.034) mediated the relationship between guidance and outcome. Finally, in a multiple mediation model both early-treatment working alliance and adherence to the program (B = -0.050) mediated the relationship between guidance and outcome. These findings indicate that guidance increases working alliance to treatment providers as early as two weeks after treatment beginning. The alliance predicts outcome and mediates the relationship between guidance and outcome. Participants' agreement with tasks and goals of a program seems to be more important than the bond with treatment providers. Treatment providers might therefore attune web-based programs to the preferences and expectations of participants. In addition to the working alliance, adherence to the program co-mediates the relationship between guidance and outcome.

Two sides of the same coin? Patient and therapist experiences with a transdiagnostic blended intervention focusing on emotion regulation.

Introduction: The combination of internet-based intervention and psychotherapy, commonly termed blended therapy (BT), has gained popularity in recent years. While advantages and disadvantages of BT have been identified from the patient and therapist perspective, the two perspectives have rarely been examined within the same treatment. Moreover, almost all available research on patient and therapist experiences with BT is disorder-specific. This study aimed to investigate patient and therapist experiences within the same transdiagnostic BT. Methods: A qualitative analysis of semi-structured interviews with eight patients and eight therapists taking part in a transdiagnostic blended intervention focusing on the topic of emotion regulation was conducted. A qualitative content analysis approach was used. Category frequencies were calculated and similarities and differences between the patient and therapist experience were explored. Results: Ten main themes and 59 subthemes were identified in the category system for patient interviews and ten main themes and 50 subthemes were identified in the category system for therapist interviews. Similarities and differences between the two perspectives were reported with regard to 1) expectations toward the intervention, 2) the internet-based intervention, 3) symptomatology and emotion regulation, 4) the therapeutic relationship and 5) the blended format. Conclusion: This study provides first insights on the experiences with transdiagnostic BT focusing on emotion regulation. Based on the results, different recommendations for the improvement of transdiagnostic BT are made. Future research on patient and therapist experiences with transdiagnostic BT is necessary, in order to further improve the experience of those involved.

Evaluating the Efficacy of a Guided and Unguided Internet-Based Self-help Intervention for Chronic Loneliness: Protocol for a 3-Arm Randomized Controlled Trial.

BACKGROUND: Loneliness, or perceived social isolation, is prevalent in both the general population and clinical practice. Although loneliness has repeatedly been associated with mental and physical health, research on interventions that reduce loneliness effectively is still rather scarce. OBJECTIVE: This study aims to evaluate the efficacy of a guided and an unguided version of the same internet-based cognitive behavioral self-help program for loneliness (SOLUS-D) for adults. METHODS: A total of 250 participants will be randomly assigned to 1 of 2 intervention groups (SOLUS-D with guidance or SOLUS-D without guidance) or a wait-list control group (2:2:1 allocation ratio). Adult participants experiencing high levels of loneliness will be recruited from the general population. Individuals currently experiencing at least moderately severe depressive symptoms, an ongoing severe substance use disorder, previous or current bipolar or psychotic disorder, or acute suicidality will be excluded from the trial. Assessments will take place at baseline, 5 weeks (midassessment), and 10 weeks (postassessment). The primary outcome is loneliness assessed using the 9-item University of California, Los Angeles Loneliness Scale at the posttreatment time point. Secondary outcomes include depressive symptoms, symptoms of social anxiety, satisfaction with life, social network size, and variables assessing cognitive bias and social behavior. The maintenance of potentially achieved gains will be assessed and compared at 6 and 12 months after randomization in the 2 active conditions. Potential moderators and mediators will be tested exploratorily. Data will be analyzed on an intention-to-treat basis. RESULTS: Recruitment and data collection started in May 2021 and are expected to be completed by 2022, with the 12-month follow-up to be completed by 2023. As of the time of submission of the manuscript, 134 participants were randomized. CONCLUSIONS: This 3-arm randomized controlled trial will add to the existing research on the efficacy of loneliness interventions. Furthermore, it will shed light on the role of human guidance in internet-based treatments for individuals with increased levels of loneliness and the possible mechanisms of change. If SOLUS-D proves effective, it could provide a low-threshold, cost-efficient method of helping and supporting individuals with increased levels of loneliness. TRIAL REGISTRATION: ClinicalTrials.gov NCT04655196; https://clinicaltrials.gov/ct2/show/NCT04655196. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36358.

A Data-Driven Clustering Method for Discovering Profiles in the Dynamics of Major Depressive Disorder Using a Smartphone-Based Ecological Momentary Assessment of Mood.

Background: Although major depressive disorder (MDD) is characterized by a pervasive negative mood, research indicates that the mood of depressed patients is rarely entirely stagnant. It is often dynamic, distinguished by highs and lows, and it is highly responsive to external and internal regulatory processes. Mood dynamics can be defined as a combination of mood variability (the magnitude of the mood changes) and emotional inertia (the speed of mood shifts). The purpose of this study is to explore various distinctive profiles in real-time monitored mood dynamics among MDD patients in routine mental healthcare. Methods: Ecological momentary assessment (EMA) data were collected as part of the cross-European E-COMPARED trial, in which approximately half of the patients were randomly assigned to receive the blended Cognitive Behavioral Therapy (bCBT). In this study a subsample of the bCBT group was included (n = 287). As part of bCBT, patients were prompted to rate their current mood (on a 1-10 scale) using a smartphone-based EMA application. During the first week of treatment, the patients were prompted to rate their mood on three separate occasions during the day. Latent profile analyses were subsequently applied to identify distinct profiles based on average mood, mood variability, and emotional inertia across the monitoring period. Results: Overall, four profiles were identified, which we labeled as: (1) "very negative and least variable mood" (n = 14) (2) "negative and moderate variable mood" (n = 204), (3) "positive and moderate variable mood" (n = 41), and (4) "negative and highest variable mood" (n = 28). The degree of emotional inertia was virtually identical across the profiles. Conclusions: The real-time monitoring conducted in the present study provides some preliminary indications of different patterns of both average mood and mood variability among MDD patients in treatment in mental health settings. Such varying patterns were not found for emotional inertia.

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.

Optimizing the context of support of web-based self-help in individuals with mild to moderate depressive symptoms: A randomized full factorial trial.

Web-based self-help programs for individuals with depressive symptoms are efficacious. Differences in effect sizes and adherence rates might be due to contextual factors. This randomized factorial trial investigated the effects of four potentially supportive contextual factors on outcome and adherence. Two factors were provided through human contact (guidance and a diagnostic interview), and two factors were provided without human contact (a motivational interviewing module and automated emails). We recruited 316 adults with mild to moderate depressive symptoms (Patient Health Questionnaire-9 score: 5-14). All participants received access to a problem-solving therapy program. Participants were randomized across the four experimental factors (present or absent), resulting in a 16-condition design. The primary outcome was depressive symptoms 10 weeks after baseline. The secondary outcome was program adherence. Overall, results showed significant symptom reduction for the primary depression measure (Cohen's d = 0.38-0.91). Guided participants showed significantly less severe symptoms of depression at post-treatment (d = 0.15) and higher treatment adherence (d = 0.53). At follow-up, these differences were no longer present. The remaining three factors did not influence primary outcome and adherence. These findings indicate that guidance leads to a faster reduction of depressive symptoms and higher treatment adherence.

Intensity of Treatment as Usual and Its Impact on the Effects of Face-to-Face and Internet-Based Psychotherapy for Depression: A Preregistered Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Treatment as usual (TAU) is the most frequently used control group in randomized trials of psychotherapy for depression. Concerns have been raised that the heterogeneity of treatments in TAU leads to biased estimates of psychotherapy efficacy and to an unclear difference between TAU and control groups like waiting list (WL). OBJECTIVE: We investigated the impact of control group intensity (i.e., amount and degree to which elements of common depression treatments are provided) on the effects of face-to-face and internet-based psychotherapy for depression. METHODS: We conducted a preregistered meta-analysis (www.osf.io/4mzyd). We included trials comparing psychotherapy with TAU or WL in patients with symptoms of unipolar depression. Six indicators were used to assess control group intensity. PRIMARY OUTCOME: Standardized mean difference (SMD) of psychotherapy and control in depressive symptoms at treatment termination. RESULTS: We included 89 trials randomizing 14,474 patients to 113 psychotherapy conditions and 89 control groups (TAU in 42 trials, WL in 47 trials). Control group intensity predicted trial results in preregistered (one-sided ps < 0.042) and exploratory analyses. Psychotherapy effects were significantly smaller (one-sided p = 0.002) in trials with higher intensity TAU (SMD = 0.324, CI 0.209 to 0.439) than in trials with lower intensity TAU (SMD = 0.628, CI 0.455 to 0.801). Psychotherapy effects against lower intensity TAU did not differ from effects against WL (two-sided p = 0.663). CONCLUSIONS: Our results suggest that variation in TAU intensity impacts the outcome of trials. More scrutiny in the design of control groups for clinical trials is recommended.

Examining the Theoretical Framework of Behavioral Activation for Major Depressive Disorder: Smartphone-Based Ecological Momentary Assessment Study.

BACKGROUND: Behavioral activation (BA), either as a stand-alone treatment or as part of cognitive behavioral therapy, has been shown to be effective for treating depression. The theoretical underpinnings of BA derive from Lewinsohn et al's theory of depression. The central premise of BA is that having patients engage in more pleasant activities leads to them experiencing more pleasure and elevates their mood, which, in turn, leads to further (behavioral) activation. However, there is a dearth of empirical evidence about the theoretical framework of BA. OBJECTIVE: This study aims to examine the assumed (temporal) associations of the 3 constructs in the theoretical framework of BA. METHODS: Data were collected as part of the "European Comparative Effectiveness Research on Internet-based Depression Treatment versus treatment-as-usual" trial among patients who were randomly assigned to receive blended cognitive behavioral therapy (bCBT). As part of bCBT, patients completed weekly assessments of their level of engagement in pleasant activities, the pleasure they experienced as a result of these activities, and their mood over the course of the treatment using a smartphone-based ecological momentary assessment (EMA) application. Longitudinal cross-lagged and cross-sectional associations of 240 patients were examined using random intercept cross-lagged panel models. RESULTS: The analyses did not reveal any statistically significant cross-lagged coefficients (all P>.05). Statistically significant cross-sectional positive associations between activities, pleasure, and mood levels were identified. Moreover, the levels of engagement in activities, pleasure, and mood slightly increased over the duration of the treatment. In addition, mood seemed to carry over, over time, while both levels of engagement in activities and pleasurable experiences did not. CONCLUSIONS: The results were partially in accordance with the theoretical framework of BA, insofar as the analyses revealed cross-sectional relationships between levels of engagement in activities, pleasurable experiences deriving from these activities, and enhanced mood. However, given that no statistically significant temporal relationships were revealed, no conclusions could be drawn about potential causality. A shorter measurement interval (eg, daily rather than weekly EMA reports) might be more attuned to detecting potential underlying temporal pathways. Future research should use an EMA methodology to further investigate temporal associations, based on theory and how treatments are presented to patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02542891, https://clinicaltrials.gov/ct2/show/NCT02542891; German Clinical Trials Register, DRKS00006866, https://tinyurl.com/ybja3xz7; Netherlands Trials Register, NTR4962, https://www.trialregister.nl/trial/4838; ClinicalTrials.Gov, NCT02389660, https://clinicaltrials.gov/ct2/show/NCT02389660; ClinicalTrials.gov, NCT02361684, https://clinicaltrials.gov/ct2/show/NCT02361684; ClinicalTrials.gov, NCT02449447, https://clinicaltrials.gov/ct2/show/NCT02449447; ClinicalTrials.gov, NCT02410616, https://clinicaltrials.gov/ct2/show/NCT02410616; ISRCTN registry, ISRCTN12388725, https://www.isrctn.com/ISRCTN12388725.