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Objective: To examine immediate and long-term effectiveness of an adjunctive Internet intervention for depression in a large sample of patients undergoing routine psychotherapy., Method: The current study evaluated a subgroup of patients from the Evident trial, a randomized investigation of a 12-week minimally guided Internet intervention (Deprexis) for the treatment of mild to moderate depression. 340 adults (mean age = 43.3 years; 71.7 % female) of the original sample received routine outpatient psychotherapy during the trial period, resulting in a standard psychotherapy group (n = 174) and an augmented therapy group (n = 166). Outcomes were assessed at baseline, post-treatment and 6-month follow-up., Results: Intention-to-treat analyses indicated that combined treatment led to a greater reduction in symptoms of depression (effect size d = 0.32; p = .002), improved therapeutic progress (d = 0.36; p = .003), and higher mental health-related quality of life (d = 0.34; p = .004). There was no intervention effect on physical health-related quality of life. The same pattern was found at 6-month follow-up, and adjunctive treatment also resulted in increased rates of clinical improvement. Treatment success was independent from therapeutic orientation of combined face-to-face therapy., Conclusion: Results indicate that the adjunctive use of the investigated intervention can produce additional and lasting effects in routine outpatient psychotherapy for mild to moderate levels of depression. The study adds to the ongoing evidence on augmented effects of blended treatment. Future studies should investigate different types of blends in diverse populations by means of change-sensitive assessment strategies., Competing Interests: Declaration of Competing Interest Björn Meyer is employed as research director at GAIA AG, the company that developed, owns and operates the Internet intervention investigated in this trial. All the other authors report no relationships with commercial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Therapeutic alliance has been well established as a robust predictor of face-to-face psychotherapy outcomes. Although initial evidence positioned alliance as a relevant predictor of internet intervention success, some conceptual and methodological concerns were raised regarding the methods and instruments used to measure the alliance in internet interventions and its association with outcomes., Objective: The aim of this study was to explore the alliance-outcome association in a guided internet intervention using a measure of alliance especially developed for and adapted to guided internet interventions, showing evidence of good psychometric properties., Methods: A sample of 223 adult participants with moderate depression received an internet intervention (ie, Deprexis) and email support. They completed the Working Alliance Inventory for Guided Internet Intervention (WAI-I) and a measure of treatment satisfaction at treatment termination and measures of depression severity and well-being at termination and 3- and 9-month follow-ups. For data analysis, we used two-level hierarchical linear modeling that included two subscales of the WAI-I (ie, tasks and goals agreement with the program and bond with the supporting therapist) as predictors of the estimated values of the outcome variables at the end of follow-up and their rate of change during the follow-up period. The same models were also used controlling for the effect of patient satisfaction with treatment., Results: We found significant effects of the tasks and goals subscale of the WAI-I on the estimated values of residual depressive symptoms (γ 02 =-1.74, standard error [SE]=0.40, 95% CI -2.52 to -0.96, t 206 =-4.37, P<.001) and patient well-being (γ 02 =3.10, SE=1.14, 95% CI 0.87-5.33, t 198 =2.72, P=.007) at the end of follow-up. A greater score in this subscale was related to lower levels of residual depressive symptoms and a higher level of well-being. However, there were no significant effects of the tasks and goals subscale on the rate of change in these variables during follow-up (depressive symptoms, P=.48; patient well-being, P=.26). The effects of the bond subscale were also nonsignificant when predicting the estimated values of depressive symptoms and well-being at the end of follow-up and the rate of change during that period (depressive symptoms, P=.08; patient well-being, P=.68)., Conclusions: The results of this study point out the importance of attuning internet interventions to patients' expectations and preferences in order to enhance their agreement with the tasks and goals of the treatment. Thus, the results support the notion that responsiveness to a patient's individual needs is crucial also in internet interventions. Nevertheless, these findings need to be replicated to establish if they can be generalized to different diagnostic groups, internet interventions, and supporting formats., (©Juan Martín Gómez Penedo, Anna Margarete Babl, Martin grosse Holtforth, Fritz Hohagen, Tobias Krieger, Wolfgang Lutz, Björn Meyer, Steffen Moritz, Jan Philipp Klein, Thomas Berger. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.03.2020.)

To date, only few studies have attempted to investigate non-ignorable dropout during Internet-based interventions by applying an NMAR model, which includes missing data indicators in its equations. Here, the Muthen-Roy model was used to investigate change and dropout patterns in a sample of patients with mild-to-moderate depression symptoms ( N = 483) who were randomized to a 12-week Internet-based intervention (deprexis, identifier: NCT01636752). Participants completed the PHQ-9 biweekly during the treatment. We identified four change-dropout patterns: Participants showing high impairment, improvement and low dropout probability (C3, N = 134) had the highest rate of reliable change at 6- and 12-month follow-up. A further pattern was characterized by high impairment, deterioration and high dropout probability (C2, N = 32), another by low impairment, improvement and high dropout probability (C1, N = 198). The last pattern was characterized by high impairment, no change and low dropout probability (C4, N = 119). In addition to deterioration, also rapid improvement may lead to dropout as a result of a perceived "good enough" dosage of treatment. This knowledge may strengthen sensitivity for the mechanisms of dropout and help to consider its meaning in efforts to optimize treatment selection.

Background: Psychological online interventions (POIs) for depression have demonstrated promising effects. However, there are fewer randomized controlled studies on POIs among older adults with depression. The goal of the present study was to compare the use and efficacy of Deprexis, an online intervention for depression, among Millennials (18-35 years) and Baby Boomers (50-65 years)., Methods: We completed a secondary data analysis on a subset (N = 577) of participants in the EVIDENT trial, a parallel-groups, pragmatic, randomized, controlled single-blind study, which compared a 12-week POI (Deprexis) to care as usual (CAU). Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The main outcome of interest was change on self-rated depression severity (PHQ-9)., Results: Compared to Millennials, Boomers used the intervention significantly more often (d = 0.45) and for a longer duration (d = 0.46), and endorsed more positive attitudes towards POIs (d = 0.14). There was no significant Age Group by Intervention Group interaction for change in PHQ-9. The post-assessment between-group effect size (intervention vs. CAU control) for Millennials and Boomers were d = 0.26 and d = 0.39, respectively, and were stable at follow-up (d = 0.37 and d = 0.39)., Limitations: Age-based dichotomization may not accurately represent participants' experiences with and use of technology., Conclusions: The POI examined in this trial was superior to CAU and was comparably effective among groups of adults defined as Millennials and Baby Boomers. Adults of the Baby Boomer generation who participate in POIs may have more positive attitudes towards POIs compared to their younger counterparts., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Most individuals with depression do not receive adequate treatment. Internet interventions may help to bridge this gap. Research on attitudes toward Internet interventions might facilitate the dissemination of such interventions by identifying factors that help or hinder uptake and implementation, and by clarifying who is likely to benefit. This study examined whether attitudes toward Internet interventions moderate the effects of a depression-focused Internet intervention, and how attitudes change over the course of treatment among those who do or do not benefit., Methods: We recruited 1,004 adults with mild-to-moderate depression symptoms and investigated how attitudes toward Internet interventions are associated with the efficacy of the program deprexis, and how attitudes in the intervention group change from pre to post over a 3 months intervention period, compared to a control group (care as usual). This study consists of a subgroup analysis of the randomized controlled EVIDENT trial., Results: Positive initial attitudes toward Internet interventions were associated with greater efficacy (η 2 p  = .014) independent of usage time, whereas a negative attitude (perceived lack of personal contact) was associated with reduced efficacy (η 2 p  = .012). Users' attitudes changed during the trial, and both the magnitude and direction of attitude change were associated with the efficacy of the program over time (η 2 p  = .030)., Conclusions: Internet interventions may be the most beneficial for individuals with positive attitudes toward them. Informing potential users about evidence-based Internet interventions might instill positive attitudes and thereby optimize the benefits such interventions can provide. Assessing attitudes prior to treatment might help identify suitable users., (© 2018 Wiley Periodicals, Inc.)

Background: Adherence to Internet interventions is often reported to be rather low and this might adversely impact the effectiveness of these interventions. We investigated if patient characteristics are associated with adherence, and if adherence is associated with treatment outcome in a large RCT of an Internet intervention for depression, the EVIDENT trial., Methods: Patients were randomized to either care as usual (CAU) or CAU plus the Internet intervention Deprexis. A total of 509 participants with mild to moderate depressive symptoms were included in the intervention group and of interest for the present study. We assessed depression symptoms pre and post intervention (12 weeks). Patient characteristics, a self-rating screening for mental disorders, attitudes towards online interventions, and quality of life were assessed before randomization., Results: Adherence in this study was good with on average seven hours of usage time and eight number of sessions spent with the intervention. Some of the patient characteristics (age, sex, depressive symptoms, and confidence in the effectiveness of the program) predicted higher number of sessions in different models (explaining in total between 15 and 25% of variance). Older age (β = .16) and higher depressive symptoms (β = .15) were associated with higher usage duration. Higher adherence to the program predicted a greater symptom reduction in depressive symptoms over 12 weeks (number of sessions: β = .13, usage duration: β = .14), however, this prediction could mostly be explained by receiving guidance (β = .27 and .26)., Limitations: Receiving guidance and symptom severity at baseline were confounded since only participants with a moderate symptom severity at baseline received e-mail support. Therefore no firm conclusions can be drawn from the association we observed between baseline symptom severity and usage intensity., Conclusions: We conclude that older age was associated with adherence and adherence was positively associated with outcome. The effects we have found were small however suggesting that adherence might also be influenced by further variables., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Internet interventions are effective in treating depressive symptoms but few studies conducted a long-term follow-up. The aim of this study was to test the effectiveness of an internet intervention in increasing the remission rate over a twelve months period., Methods: A total of 1013 participants with mild to moderate depressive symptoms were randomized to either care as usual alone or a 12-week internet intervention (Deprexis) plus usual care. Self-rated depression severity (PHQ-9) was assessed regularly over twelve months., Results: Remission rates over time were significantly higher in the intervention group (Cox regression: hazard ratio [HR] 1.31; p = 0.009). The intervention was more effective in the subgroup not taking antidepressant medication (Cox regression: HR 1.88; p < 0.001). PHQ-change from baseline was greater in the intervention group (linear mixed model [LMM]: p < 0.001) with the between-group effect gradually decreasing from d = 0.36 at three months to d = 0.13 at twelve months (LMM: group by time interaction: p < 0.001)., Conclusion: This internet intervention can contribute to achieving remission in people with mild to moderate depressive symptoms, especially if they are not on antidepressant medication (Trial Registration: NCT01636752)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: This study aims to examine whether the effects of internet interventions for depression generalise to participants recruited in clinical settings., Design: This study uses subgroup analysis of the results of a randomised, controlled, single-blind trial., Setting: The study takes place in five diagnostic centres in Germany., Participants: A total of 1013 people with mild to moderate depressive symptoms were recruited from clinical sources as well as internet forums, statutory insurance companies and other sources., Interventions: This study uses either care-as-usual alone (control) or a 12-week internet intervention (Deprexis) plus usual care (intervention)., Main Outcome Measures: The primary outcome measure was self-rated depression severity (Patient Health Questionnaire-9) at 3 months and 6 months. Further measures ranged from demographic and clinical parameters to a measure of attitudes towards internet interventions (Attitudes towards Psychological Online Interventions Questionnaire)., Results: The recruitment source was only associated with very few of the examined demographic and clinical characteristics. Compared with participants recruited from clinical sources, participants recruited through insurance companies were more likely to be employed. Clinically recruited participants were as severely affected as those from other recruitment sources but more sceptical of internet interventions. The effectiveness of the intervention was not differentially associated with recruitment source (treatment by recruitment source interaction=0.28, p=0.84)., Conclusion: Our results support the hypothesis that the intervention we studied is effective across different recruitment sources including clinical settings., Trial Registration Number: ClinicalTrials.gov NCT01636752., Competing Interests: Competing interests: JPK received funding for clinical trials (German Federal Ministry of Health, Servier - distributor of the internet intervention “Deprexis"), payments for presentations on internet interventions (Servier) and payments for workshops and books (Beltz, Elsevier and Hogrefe) on psychotherapy for chronic depression and on psychiatric emergencies. BM is employed as research director at GAIA AG, the company that developed, owns and operates the internet intervention “Deprexis”. MH is a consultant of Servier. He was an invited speaker at several workshops and continuous education workshops over the last two years. All the other authors report no relationships with commercial interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Web-based interventions for individuals with depressive disorders have been a recent focus of research and may be an effective adjunct to face-to-face psychotherapy or pharmacological treatment., Objective: The aim of our study was to examine the early change patterns in Web-based interventions to identify differential effects., Methods: We applied piecewise growth mixture modeling (PGMM) to identify different latent classes of early change in individuals with mild-to-moderate depression (n=409) who underwent a CBT-based web intervention for depression., Results: Overall, three latent classes were identified (N=409): Two early response classes (n=158, n=185) and one early deterioration class (n=66). Latent classes differed in terms of outcome (P<.001) and adherence (P=.03) in regard to the number of modules (number of modules with a duration of at least 10 minutes) and the number of assessments (P<.001), but not in regard to the overall amount of time using the system. Class membership significantly improved outcome prediction by 24.8% over patient intake characteristics (P<.001) and significantly added to the prediction of adherence (P=.04)., Conclusions: These findings suggest that in Web-based interventions outcome and adherence can be predicted by patterns of early change, which can inform treatment decisions and potentially help optimize the allocation of scarce clinical resources., (©Wolfgang Lutz, Alice Arndt, Julian Rubel, Thomas Berger, Johanna Schröder, Christina Späth, Björn Meyer, Wolfgang Greiner, Viola Gräfe, Martin Hautzinger, Kristina Fuhr, Matthias Rose, Sandra Nolte, Bernd Löwe, Fritz Hohagen, Jan Philipp Klein, Steffen Moritz. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.06.2017.)

Background: Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults., Methods: This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical settings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models., Results: A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed signixFB01;cantly between groups (t825 = 6.12, p < 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was d = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with d = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10)., Conclusions: The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications., (© 2016 S. Karger AG, Basel.)

Objective: Low platelet monoaminoxidase B (MAO-B) activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between MAO-B activity in platelets and aspects of suicidality in depressed patients and controls., Method: In 87 patients with affective spectrum disorders (58% suffering from a major depressive episode - MDE) the potential association between platelet MAO-B activity and suicidality was examined. Fifty-nine of the patients had committed suicide attempt recently (SA -'suicide attempters'), 28 patients were acutely depressed without having shown suicidal thoughts or suicidal behaviour in the past (NA -'non-suicide attempters')., Results: The SA and NA were comparable as to their diagnoses and general demographic and psychopathological parameters. MAO-B activity did not differ between SA and NA. No systematic correlations existed between MAO-B activity and any dimensions of suicidal behaviour or psychopathology. As a single finding only a weak positive association of higher MAO-B activity in SA with a fatal intention of the SA was observed., Conclusion: Our findings do not support a consistent association of platelet MAO-B activity and suicidal behaviour in general, but specific facts of suicidality might be associated.

Background: A new observer depression scale which is based on the descriptive operationalized classification principles of ICD-10 is introduced. The AMDP Depression Scale (AMDP-DS), a 22-item clinician-rated inventory, provides the opportunity of dimensional as well as categorical depression severity assessment., Methods: A sample of 50 patients with depressive symptoms were assessed with the AMDP-DS by two raters in a joint rater session. A number of widely used depression scales were applied separately by an independent rater. The ICD-10 symptom checklist was used for categorical assessment of depressive disorders., Results: The inter-rater reliability for the total score of the AMDP-DS was excellent (Intraclass coefficient: 0.97). There were high correlations with the sum scores of the other scales under study. The correlations between the ICD-10 symptom-checklist and the AMDP-DS ranged from 0.75 to 0.89 for the total sample and 0.44 to 0.51 for patients with acute depressive episode., Limitations: The results are limited by the method of a joint rater setting and the relatively small subsample of patients with depressive episode., Conclusions: The AMDP-DS satisfies the requirements of psychometric criteria with a sufficient degree. A new depression scale designed to cover dimensional as well as categorical aspects has successfully been developed.

Pseudodementia as a common trait in elderly depressives presents a major problem in gerontopsychiatry, especially for the differential diagnosis between Old-Age Depression (OAD) and Dementia of the Alzheimer Type (DAT). The present polysomnographic study examined parameters of sleep continuity, sleep architecture, and REM sleep to differentiate DAT from OAD. The investigation was based on the theoretical framework of the cholinergic-aminergic imbalance model of depression, the cholinergic deficit hypothesis of Alzheimer's disease and the reciprocal interaction model of Non-REM/REM sleep regulation, according to which REM sleep parameters should have high discriminative value to differentiate OAD and DAT. We investigated 35 DAT patients, 39 OAD patients and 42 healthy controls for two consecutive nights in the sleep laboratory. The DAT patients were in relatively early/mild stages of the disease, the severity of depression in the OAD group was moderate to severe. Depressed patients showed characteristic 'depression-like' EEG sleep alterations, i.e. a lower sleep efficiency, a higher amount of nocturnal awakenings and decreased sleep stage 2. Sleep continuity and architecture in DAT was less disturbed. Nearly all REM sleep measures differentiated significantly between the diagnostic groups. OAD patients showed a shortened REM latency, increased REM density and a high rate of Sleep Onset REM periods (SOREM), whereas in DAT REM density was decreased in comparison to control subjects. REM latency in DAT was not prolonged as expected. To assess the discriminative power of REM sleep variables a series of discriminant analyses were conducted. Overall, 86% of patients were correctly classified, using REM density and REM latency measures. Our findings suggest that REM density as an indicator of phasic activity appears to be more sensitive as a biological marker for the differential diagnosis of OAD and DAT than REM latency. The results support the role of central cholinergic neurotransmission in REM sleep regulation and the pathogenesis of DAT and OAD.