Maintaining Outcomes of Internet-Delivered Cognitive-Behavioral Therapy for Depression: A Network Analysis of Follow-Up Effects.

Background: Depression is a highly prevalent mental disorder, but only a fraction of those affected receive evidence-based treatments. Recently, Internet-based interventions were introduced as an efficacious and cost-effective approach. However, even though depression is a heterogenous construct, effects of treatments have mostly been determined using aggregated symptom scores. This carries the risk of concealing important effects and working mechanisms of those treatments. Methods: In this study, we analyze outcome and long-term follow-up data from the EVIDENT study, a large (N = 1,013) randomized-controlled trial comparing an Internet intervention for depression (Deprexis) with care as usual. We use Network Intervention Analysis to examine the symptom-specific effects of the intervention. Using data from intermediary and long-term assessments that have been conducted over 36 months, we intend to reveal how the treatment effects unfold sequentially and are maintained. Results: Item-level analysis showed that scale-level effects can be explained by small item-level effects on most depressive symptoms at all points of assessment. Higher scores on these items at baseline predicted overall symptom reduction throughout the whole assessment period. Network intervention analysis offered insights into potential working mechanisms: while deprexis directly affected certain symptoms of depression (e.g., worthlessness and fatigue) and certain aspects of the quality of life (e.g., overall impairment through emotional problems), other domains were affected indirectly (e.g., depressed mood and concentration as well as activity level). The configuration of direct and indirect effects replicates previous findings from another study examining the same intervention. Conclusions: Internet interventions for depression are not only effective in the short term, but also exert long-term effects. Their effects are likely to affect only a small subset of problems. Patients reporting these problems are likely to benefit more from the intervention. Future studies on online interventions should examine symptom-specific effects as they potentially reveal the potential of treatment tailoring. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT02178631.

Immediate and long-term effectiveness of adding an Internet intervention for depression to routine outpatient psychotherapy: Subgroup analysis of the EVIDENT trial.

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.

The Association of Therapeutic Alliance With Long-Term Outcome in a Guided Internet Intervention for Depression: Secondary Analysis From a Randomized Control Trial.

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 (γ02=-1.74, standard error [SE]=0.40, 95% CI -2.52 to -0.96, t206=-4.37, P<.001) and patient well-being (γ02=3.10, SE=1.14, 95% CI 0.87-5.33, t198=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.

Identifying change-dropout patterns during an Internet-based intervention for depression by applying the Muthen-Roy model.

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.

The Working Alliance Inventory for guided Internet interventions (WAI-I).

OBJECTIVE: This study analyses the psychometric properties of the Working Alliance Inventory adapted for guided Internet interventions (WAI-I). METHODS: We drew on the data set from a multicenter trial that examined a guided Internet intervention (deprexis) for patients with mild to moderate depression. Two hundred twenty-three patients completed the WAI-I and the Patient Satisfaction Questionnaire (ZUF-8) at posttreatment, and the Attitudes toward Psychological Online-Interventions Questionnaire (APOI) at baseline. We ran confirmatory factor analyses (CFA) testing two- and three-factor solutions and calculated Cronbach's α, item-total correlations, and correlations of the WAI-I with APOI and ZUF-8. RESULTS: The results suggested a two-factor solution, with a very good model fit and evidence of factor independency, adequate internal consistency, and external validity for the complete scale and the sub-scales. CONCLUSIONS: The WAI-I showed as a reliable and valid instrument to capture alliance in guided Internet interventions, which might facilitate process-outcome research and treatment development efforts.

Social phobia moderates the outcome in the EVIDENT study: A randomized controlled trial on an Internet-based psychological intervention for mild to moderate depressive symptoms.

OBJECTIVE: Data from the EVIDENT trial were reanalyzed to examine whether specific anxiety-related comorbidities moderate the effect of an Internet intervention on depression outcome. METHOD: The EVIDENT study is a randomized controlled trial that included N = 1,013 participants with mild to moderate depressive symptoms (i.e., scores between 5 and 14 on the Patient Health Questionnaire-9 [PHQ-9]) who were randomized to a control group with access to care-as-usual (n = 504) or to an intervention group, which accessed the Internet intervention Deprexis adjunctively to care-as-usual (n = 509). Anxiety-related comorbidities (generalized anxiety disorder, social phobia, panic disorder, agoraphobia, panic disorder with agoraphobia, specific phobia, posttraumatic stress disorder, obsessive-compulsive disorder) were assessed with the Web Screening Questionnaire at baseline. Multilevel models were performed. RESULTS: Twelve potential moderators (8 specific anxiety-related comorbidities, depression severity, and 3 previously identified moderators in the EVIDENT trial) were examined within 1 multilevel model, and only social phobia moderated the intervention effect on depression outcome (in favor of Deprexis). This moderating effect of social phobia did not depend on the other moderators' being included in the model. These results emerged for continuous PHQ-9 scores as well as for clinically important PHQ-9 changes as outcome (p < .05). However, moderating effects did not reach small effect sizes, accounted for less than 1% of the variance in change in depressive symptoms, and showed limited reproducibility in randomly selected split halves. CONCLUSIONS: Deprexis appears to be most effective for participants with mild to moderate depressive symptoms and comorbid social phobia, but further replications of this finding are necessary. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Health economic evaluation of a web-based intervention for depression: the EVIDENT-trial, a randomized controlled study.

BACKGROUND: Depression often remains undiagnosed or treated inadequately. Web-based interventions for depression may improve accessibility of treatment and reduce disease-related costs. This study aimed to examine the potential of the web-based cognitive behavioral intervention "deprexis" in reducing disease-related costs. METHODS: Participants with mild to moderate depressive symptoms were recruited and randomized to either a 12-week web-based intervention (deprexis) in addition to care as usual (intervention group) or care as usual (control group). Outcome measures were health-related resource use, use of medication and incapacity to work as well as relating direct health care costs. Outcomes were assessed on patients' self-report at baseline, three months and six months. RESULTS: A total of 1013 participants were randomized. In both groups total direct health care costs decreased during the study period, but changes from baseline did not significantly differ between study groups. Numeric differences between study groups existed in outpatient treatment costs. They could be attributed to differences in changes of costs for psychotherapeutic treatment from baseline. Whereas costs for psychotherapeutic treatment decreased in the intervention group, costs increased in the control group (- 16.8% (€80) vs. + 14.7% (€60)) (tdf = 685 = 2.57; p = 0.008). CONCLUSION: The study indicates the health economic potential of innovative e-mental-health programs. There is evidence to suggest that the use of deprexis over a period of 12 weeks leads to a decrease in outpatient treatment cost, especially in those related to different types of psychotherapeutic treatment.

[Self-management interventions in the treatment of depressive disorders: ready for clinical practice?] / Selbstmanagement Interventionen in der Behandlung depressiver Störungen: reif für die klinische Praxis?

Only about half of those suffering from a depressive disorder seek treatment. Self-management interventions are one way to reduce this treatment gap. These interventions are mostly based on evidence-based techniques of cognitive behavioural therapy, which are taught by a computer program instead of a therapist. Numerous studies have shown the effectiveness of these interventions. However, these studies also raise a number of questions. These concern the efficacy both in the external rating and in the long-term course and the efficacy in severe depressive symptoms or in combination with antidepressant medication. Finally, the question arises as to the use of these interventions in patients in clinical practice and in people who are not particularly Internet-savvy. We addressed these questions in a large randomized study (EVIDENT study). This study investigated the efficacy of Intervention deprexis®. The results of this study are summarised in this overview and placed in the context of other interventions available in Germany.

[Psychotherapy of Depression as Neurobiological Process - Evidence from Neuroimaging]. / Psychotherapie depressiver Störungen als neurobiologischer Prozess ­ Erkenntnisse aus der Hirnbildgebung.

Research on neurobiological effects of psychotherapy in depression facilitates the improvement of treatment strategies. The cortico-limbic dysregulation model serves as a framework for numerous studies on neurobiological changes in depression. In this model, depression is described as hypoactivation of dorsal cortical brain regions in conjunction with hyperactivation of ventral paralimbic regions. This assumption has been supported by various studies of structural and functional brain abnormalities in depression. However, also regions not included in the original cortico-limbic dysregulation model, such as the dorsomedial prefrontal cortex, seem to play an important role in depression. Functional connectivity studies of depression have revealed an enhanced connectivity within the so-called default mode network which is involved in self-referential thinking. Studies also point to a normalization of limbic and cortical brain activity, especially in the anterior cingulate cortex, during psychotherapy. Some neurobiological markers like the activity of the anterior cingulate cortex, striatum and insula as well as hippocampal volume have been proposed to predict treatment response on a group-level. The activity of the anterior insula appears to be a candidate bio-marker for differential indication for psychotherapy or pharmacotherapy. The cortico-limbic dysregulation model and following research have inspired new forms of treatment for depression like deep brain stimulation of the subgenual anterior cingulate cortex, repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex, neurofeedback and attention training.

Bridging the "digital divide": A comparison of use and effectiveness of an online intervention for depression between Baby Boomers and Millennials.

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.

Impact and change of attitudes toward Internet interventions within a randomized controlled trial on individuals with depression symptoms.

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 (η2p  = .014) independent of usage time, whereas a negative attitude (perceived lack of personal contact) was associated with reduced efficacy (η2p  = .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 (η2p  = .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.

The association between adherence and outcome in an Internet intervention for depression.

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 (ß = .16) and higher depressive symptoms (ß = .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: ß = .13, usage duration: ß = .14), however, this prediction could mostly be explained by receiving guidance (ß = .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.

Time to remission from mild to moderate depressive symptoms: One year results from the EVIDENT-study, an RCT of an internet intervention for depression.

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).

Does recruitment source moderate treatment effectiveness? A subgroup analysis from the EVIDENT study, a randomised controlled trial of an internet intervention for depressive symptoms.

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.

Defining and Predicting Patterns of Early Response in a Web-Based Intervention for Depression.

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.

The regression discontinuity design showed to be a valid alternative to a randomized controlled trial for estimating treatment effects.

OBJECTIVES: To compare treatment effect estimates obtained from a regression discontinuity (RD) design with results from an actual randomized controlled trial (RCT). STUDY DESIGN AND SETTING: Data from an RCT (EVIDENT), which studied the effect of an Internet intervention on depressive symptoms measured with the Patient Health Questionnaire (PHQ-9), were used to perform an RD analysis, in which treatment allocation was determined by a cutoff value at baseline (PHQ-9 = 10). A linear regression model was fitted to the data, selecting participants above the cutoff who had received the intervention (n = 317) and control participants below the cutoff (n = 187). Outcome was PHQ-9 sum score 12 weeks after baseline. Robustness of the effect estimate was studied; the estimate was compared with the RCT treatment effect. RESULTS: The final regression model showed a regression coefficient of -2.29 [95% confidence interval (CI): -3.72 to -.85] compared with a treatment effect found in the RCT of -1.57 (95% CI: -2.07 to -1.07). CONCLUSION: Although the estimates obtained from two designs are not equal, their confidence intervals overlap, suggesting that an RD design can be a valid alternative for RCTs. This finding is particularly important for situations where an RCT may not be feasible or ethical as is often the case in clinical research settings.

Feasibility of Group Schema Therapy for Outpatients with Severe Borderline Personality Disorder in Germany: A Pilot Study with Three Year Follow-Up.

Borderline Personality Disorder (BPD) is a severe, challenging to treat mental disorder. Schema therapy (ST) as an individual therapy has been proven to be an effective psychological treatment for BPD. A group format of ST (GST) has been developed and evaluated in a randomized controlled trial in the United States and piloted in The Netherlands. These results suggest that GST speeds up and amplifies treatment effects of ST and might reduce delivery costs. However, feasibility in the German health care system and with BPD patients with high BPD severity and comorbidity, and frequent hospitalization, has not been tested to date. We investigated GST in 10 severely impaired, highly comorbid female patients with BPD, that needed frequent hospital admission. Patients received an outpatient ST-treatment program with weekly group and individual sessions for 1 year. Outcome measures including BPD severity, general psychopathology, psychosocial functioning, quality of life, happiness, schemas, and modes, and days of hospitalization were assessed at the start of treatment and 6, 12, and 36 months later with semi-structured interviews and self-report measures. We observed significant decreases in severity of BPD symptoms, general symptom severity, dysfunctional BPD-specific modes and schemas, and days of hospitalization. Functional modes, quality of live and happiness improved. The results of this feasibility study are promising and encourage further implementation of ST outpatient treatment programs even for patients with severe BPD and high hospitalization risk. However, small sample size and the missing of a control group do not allow the generalizability of these findings.

Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial.

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.