Digital interventions for common mental disorders across the lifespan: Exploring active ingredients and mechanisms of change

Common mental disorders (CMD), such as depression and anxiety, are among the main contributors to the global burden of disease across age groups. Although a range of evidence-based psychotherapeutic interventions for these prevalent disorders exist, many patients receive no empirically-supported psychotherapeutic intervention due to the unavailability of mental health care services and other significant structural and individual barriers to treatment. Digital mental health interventions might represent an important approach to overcome this treatment gap and extend evidence-based psychotherapeutic service provisions, given some specific features like delivery independent from space and time, potential cost-effectiveness, scalability as well as possible anonymity. While the efficacy and effectiveness of digital interventions for most CMD in different age groups are established by dozens of randomized controlled trials (RCT) by now, comprehensive knowledge on the active ingredients and mechanisms of change in these interventions is still lacking. Insights on the active ingredients, mediators and working mechanisms is of high scientific and clinical relevance though, as it can inform the empirically-supported advancement of interventions and clinical practices, striving for augmented and efficient interventions with better treatment outcomes. As such, the overarching aim of this dissertation is to contribute to the knowledge on the active ingredients and processes of change in digital interventions for CMD across the lifespan, enhancing our understandings whereby and how these interventions work. To this end, a series of studies building on different methodologies were conducted, in order to meet the specific research questions at hand – with a particular focus on systematic reviews and meta-analyses of RCTs, providing the most comprehensive and best-available evidence. In specific, part I of this dissertation describes the systematic evaluation of the efficacy, effectiveness and quality of internet- and mobile-based interventions for different CMD across age groups with limited evidence so far (Chapters 1-4). These chapters contribute to the evaluation of the efficacy and effectiveness of digital interventions, since the establishment that these interventions work is a fundamental prerequisite for all subsequent research on change mechanisms. Part II designates a conceptual and integrative psychological model of the mechanisms of change in digital interventions for depression as a principal framework for (digitalized) research on psychotherapy processes (Chapter 5). In part III, the novel possibilities as well as the challenges of digitalized approaches to psychotherapy process research are outlined and discussed in a perspective paper (Chapter 6). Part IV describes the results of a systematic review and meta-analysis on the incremental effects of distinct intervention components of digital interventions for anxiety disorders in adults (Chapter 7). Part V can be conceived as the heart of this dissertation and is dedicated to the mediators and mechanisms of change in digital interventions in four different settings: for the prevention of depression in patients with chronic back pain (Chapter 8), for several CMD in youth (Chapter 9), as well as for the psychological treatment of anxiety (Chapter 10) and depression (Chapter 11) in adults. These studies rely on three different methodologies, namely a secondary analysis of a multicenter RCT, two systematic reviews and a meta-analytic structural equation modeling approach. Overall, the results of this dissertation highlight that: (a) Digital interventions are effective for a range of CMD across the lifespan, with a robust trend of smaller effect sizes in unguided interventions (compared to guided interventions) and in interventions for younger age groups (i.e., adults > adolescents > children). (b) Uncertainties exist around the efficacy of mobile-based interventions. (c) A range of intervention components contribute to the efficacy of internet-based interventions, with an overarching importance of human guidance and modules that support the active coping of patients. (d) The qualification of e-coaches, the respective theoretical background and the disorder-specificity of interventions may not make a difference for the efficacy in anxiety disorders, as suggested by further meta-analytical evaluations. (e) A variety of distinct mediators transmit the efficacy of interventions, with cognitive factors appearing to be of particular relevance in depression and anxiety disorders. (f) Across studies, the best established, significant mediators are acceptance, mindfulness, self-efficacy, reductions in dysfunctional cognitions, perceived control and mastery, as well as emotion regulation particularly in youth. Finally, in part VI, the findings of this dissertation are integrated and discussed. Furthermore, implications for future research and methodological recommendations for forthcoming studies with more pertinent designs, allowing for inferences with higher causal certainty, are provided.Depression und Angststörungen gehören über alle Altersgruppen hinweg zu den häufigsten psychischen Störungen und tragen substantiell zur weltweiten Krankheitslast bei. Obgleich eine Reihe von evidenz-basierten psychotherapeutischen Interventionen für diese prävalenten Erkrankungen vorliegen, erhält eine Vielzahl von Patient:innen keine empirisch-fundierte Intervention aufgrund nur unzureichend zur Verfügung stehender psychotherapeutischer Versorgungsangebote sowie weiterer bedeutender struktureller und individueller Barrieren, welche einer Behandlung entgegenstehen. Digitale psychotherapeutische Interventionen könnten einen bedeutsamen Beitrag zur Überwindung dieser Versorgungslücke leisten und zu einer Ausweitung psychotherapeutischer Behandlungsangebote führen. Dabei dürften manche ihrer spezifischen Eigenschaften zum Tragen kommen, wie etwa die Nutzungsmöglichkeit rund um die Uhr losgelöst von räumlichen Beschränkungen, der potentiellen Kosten-Effektivität, Skalierbarkeit sowie möglichen Anonymität in der Umsetzung. Wenngleich die Wirksamkeit digitaler psychotherapeutischer Interventionen für die meisten häufigen psychischen Störungen in verschiedenen Altersgruppen durch zahlreiche randomisiert-kontrollierte Studien (RCT) zwischenzeitlich als gut belegt anzusehen ist, besteht immer noch ein Mangel an fundiertem Wissen über deren Wirkfaktoren und Veränderungsmechanismen. Ein umfassendes und vertieftes Verständnis über die therapeutisch-relevanten Wirkfaktoren, Mediatoren und spezifischen Wirkungsweisen wäre jedoch von hoher wissenschaftlicher und klinischer Bedeutung, da diese Erkenntnisse eine empirisch-begründete Weiterentwicklung der Interventionen und klinischen Praxis ermöglichen würden. Darüber könnte ein wichtiger Beitrag zu optimierten und effizienteren Interventionen mit verbesserten Behandlungsergebnissen geleistet werden. Das übergeordnete Ziel dieser Dissertation besteht dementsprechend darin, zu einem erweiterten und vertieften empirisch-begründeten Wissen über die therapeutisch-aktiven Wirkfaktoren und Veränderungsmechanismen digitaler Interventionen für häufige psychische Erkrankungen über die Lebensspanne beizutragen, und damit unser Verständnis zu verbessern, wodurch und auf welche Weisen diese Interventionen wirken. Um dieses übergeordnete Ziel zu erreichen und um die jeweiligen spezifischen Forschungsfragen der einzelnen Untersuchungen so gut wie möglich beantworten zu können, wurde eine Reihe von Studien mit unterschiedlicher Methodologie durchgeführt – mit einem besonderen Schwerpunkt auf systematischen Übersichtsarbeiten und Meta-Analysen von RCTs, da diese die umfassendste und aussagekräftigste Evidenz aufbereiten und erbringen können. Im einzelnen widmet sich der erste Teil dieser Dissertation der systematischen Evaluation der Wirksamkeit und Qualität von Internet- und mobile-basierten Interventionen (IMIs) für verschiedene häufige psychische Störungen in unterschiedlichen Altersgruppen für welche bislang nur eine eingeschränkte empirische Evidenz vorgelegen hat (Kapitel 1-4). Diese vier Veröffentlichungen tragen damit grundlegend zur Evaluation der Wirksamkeit unter Labor- und Routine-Bedingungen bei, da der Nachweis dass diese Interventionen wirksam sind als eine notwendige Vorbedingung für nachfolgende Forschung über deren Wirkungsweisen angesehen werden kann. Der zweite Teil befasst sich mit der Entwicklung eines konzeptuellen und integrativen psychologischen Models über die Veränderungsmechanismen digitaler Interventionen für depressive Störungen als Rahmenwerk für die (digitalisierte) Psychotherapieprozessforschung (Kapitel 5). Im dritten Teil der Arbeit wird den Chancen und Grenzen von digitalisierten Ansätzen im Feld der Psychotherapieprozessforschung nachgegangen und diese in einem Perspektivenartikel kritisch diskutiert (Kapitel 6). Der vierte Teil beschreibt die Ergebnisse einer Meta-Analyse zu den Effekten einzelner Interventionskomponenten von IMIs gegen Angststörungen (Kapitel 7). Der fünfte Teil – welcher als Herzstück dieser Dissertation angesehen werden kann – widmet sich den Mediatoren und Veränderungsmechanismen digitaler Interventionen in vier verschiedenen Anwendungsbereichen: für die Prävention von depressiven Störungen bei Patient:innen mit chronischen Rückenschmerzen (Kapitel 8), für eine Reihe von häufigen psychischen Störungen im Kindes- und Jugendalter (Kapitel 9), sowie bei der psychotherapeutischen Behandlung von Angststörungen (Kapitel 10) und Depression (Kapitel 11) im Erwachsenenalter. Dabei kommen drei verschiedene Studiendesigns zum Einsatz: eine Sekundäranalyse eines multizentrischen RCTs, zwei systematische Übersichtsarbeiten und ein meta-analytischer Strukturgleichungsansatz. Schließlich werden im sechsten und letzten Teil dieser Dissertation die Ergebnisse integriert und zusammenfassend diskutiert. Alles in allem deuten die Befunde dieser Dissertation daraufhin, dass: (a) Digitale Interventionen für die wichtigsten häufigen psychischen Störungen über die Lebensspanne wirksam sind, und einen robusten Trend zu geringeren Effektstärken bei therapeutisch unbegleiteten (im Vergleich zu begleiteten) Interventionen sowie bei jüngeren Altersgruppen (Erwachsene > Jugendliche > Kinder) aufweisen. (b) Nach wie vor erhebliche Unsicherheiten hinsichtlich der Wirksamkeit von Smartphone-basierten Interventionen bestehen. (c) Unterschiedliche Interventionskomponenten zur Wirksamkeit internet-basierter Interventionen beitragen – mit einer herausragenden Bedeutung von menschlicher Unterstützung und Komponenten, welche aktive Bewältigungsstrategien der Patient:innen befördern. (d) Der jeweilige therapeutische Hintergrund und die Störungsspezifität der Intervention sowie das Qualifikationsniveau unterstützender Fachkräfte (sogenannte e-Coaches) keinen Unterschied für die Wirksamkeit digitaler Interventionen bei Angststörungen machen könnten, so wie dies weitere meta-analytische Vergleiche andeuten. (e) Eine Reihe unterschiedlicher Mediatoren die Wirkung der Interventionen vermitteln, und dabei kognitiven Mediatoren bei Depression und Angststörungen offenbar eine herausgehobene Bedeutung zukommt. (f) Über alle Studien und Altersklassen hinweg Selbstwirksamkeit, Akzeptanz, Achtsamkeit, Reduktionen in dysfunktionalen Kognitionen, wahrgenommene Kontrolle sowie Emotionsregulation (insbesondere bei Jugendlichen) als am besten abgesicherte Mediatoren erscheinen. Abschließend werden im Rahmen dieser Dissertation Implikationen für zukünftige Forschung und Empfehlungen für die Methodik kommender Studien abgeleitet und diskutiert, die zu weitreichenderen und robusteren Kausalschlüssen beitragen können

Mechanisms of change in internet- and mobile-based interventions for adult anxiety disorders: A systematic review and meta-analysis protocol

Systematic Review and Meta-Analysi

Study protocol_Efficacy of Digital Health Interventions in Youth with Chronic Conditions_submitted on 2019-05-15

This study protocol was submitted to PROSPERO on May 15, 201

Mechanisms of change in digital interventions for depression: Protocol for an individual participant data meta-analysis

Digital interventions for depression might have the potential to extend and augment evidence-based treatements for this common mental disorder. Although the efficacy of digital interventions for depressive disorders is well established (Karyotaki et al., 2017; Karyotaki et al., 2018; Karyotaki et al., 2021; Königbauer et al., 2017; Reins et al., 2020), comprehensive and integrated knowledge about their mechanisms of change is largely pending. Precise information on the mediators and mechanisms of change in these interventions is crucial, in order to advance intervention development and clinical practice, contributing to more effective interventions and improved treatment outcomes (Domhardt, Cuijpers et al., 2021; Domhardt, Steubl et al., 2021). The project "Mechanisms of change in internet- and mobile-based interventions for depression: A systematic review and meta-analysis of individual participant data (howIMIwork)" is funded by the German Federal Ministry of Education and Research (BMBF; Grant Identification FKZ 01KG1802). References: Domhardt, M., Cuijpers, P., Ebert, D. D., & Baumeister, H. (2021). More Light? Opportunities and Pitfalls in Digitalized Psychotherapy Process Research. Frontiers in Psychology, 12, 544129. https://doi.org/10.3389/fpsyg.2021.544129 Domhardt, M., Steubl, L., Boettcher, J., Buntrock, C., Karyotaki, E., Ebert, D. D., Cuijpers, P., & Baumeister, H. (2021). Mediators and mechanisms of change in internet- and mobile-based interventions for depression: A systematic review. Clinical Psychology Review, 83, 101953. https://doi.org/10.1016/j.cpr.2020.101953 Karyotaki, E., Riper, H., Twisk, J., Hoogendoorn, A., Kleiboer, A., Mira, A., Mackinnon, A., Meyer, B., Botella, C., Littlewood, E., Andersson, G., Christensen, H., Klein, J. P., Schroder, J., Breton-Lopez, J., Scheider, J., Griffiths, K., Farrer, L., Huibers, M. J., . . . Cuijpers, P. (2017). Efficacy of Self-guided Internet-Based Cognitive Behavioral Therapy in the Treatment of Depressive Symptoms: A Meta-analysis of Individual Participant Data. JAMA Psychiatry, 74(4), 351–359. https://doi.org/10.1001/jamapsychiatry.2017.0044 Karyotaki, E., Ebert, D. D., Donkin, L., Riper, H., Twisk, J., Burger, S., Rozental, A., Lange, A., Williams, A. D., Zarski, A. C., Geraedts, A., van Straten, A., Kleiboer, A., Meyer, B., Ünlü Ince, B. B., Buntrock, C., Lehr, D., Snoek, F. J., Andrews, G., . . . Cuijpers, P. (2018). Do guided internet-based interventions result in clinically relevant changes for patients with depression? An individual participant data meta-analysis. Clinical Psychology Review, 63, 80–92. https://doi.org/10.1016/j.cpr.2018.06.007 Karyotaki, E., Efthimiou, O., Miguel, C., Bermpohl, F. M. G., Furukawa, T. A., Cuijpers, P., Riper, H., Patel, V., Mira, A., Gemmil, A. W., Yeung, A. S., Lange, A., Williams, A. D., Mackinnon, A., Geraedts, A., van Straten, A., Meyer, B., Björkelund, C., Knaevelsrud, C., . . . Forsell, Y. (2021). Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis. JAMA Psychiatry, 78(4), 361–371. https://doi.org/10.1001/jamapsychiatry.2020.4364 Königbauer, J., Letsch, J., Doebler, P., Ebert, D. D., & Baumeister, H. (2017). Internet- and mobile-based depression interventions for people with diagnosed depression: A systematic review and meta-analysis. Journal of Affective Disorders, 223, 28–40. https://doi.org/10.1016/j.jad.2017.07.021 Reins, J. A., Buntrock, C., Zimmermann, J., Grund, S., Harrer, M., Lehr, D., Baumeister, H., Weisel, K., Domhardt, M., Imamura, K., Kawakami, N., Spek, V., Nobis, S., Snoek, F., Cuijpers, P., Klein, J. P., Moritz, S., & Ebert, D. D. (2020). Efficacy and Moderators of Internet-Based Interventions in Adults with Subthreshold Depression: An Individual Participant Data Meta-Analysis of Randomized Controlled Trials. Psychotherapy and Psychosomatics, 1–13. https://doi.org/10.1159/00050781

Mechanisms of change in Internet- and mobile-based interventions for PTSD: a systematic review and meta-analysis

Background: While Internet- and mobile-based interventions (IMIs) are potential options to increase the access to evidence-based therapies for post-traumatic stress disorder (PTSD), comprehensive knowledge on their working mechanisms is still scarce. Objective: We aimed to evaluate studies investigating the efficacy and mechanisms of change in IMIs for adults with PTSD. Method: In this systematic review and meta-analysis (PROSPERO CRD42019130314), five databases were consulted to identify relevant studies, complemented by forward (i.e. citation search) and backward (i.e. review of reference lists from included studies) searches. Randomized controlled trials (RCTs) investigating the efficacy of IMIs compared to active controls, as well as component and mediation studies were included. Two independent reviewers extracted the data and assessed the risk of bias and requirements for process research. Random-effects meta-analyses on PTSD symptom severity as primary outcome were conducted and further information was synthesized qualitatively. Results: In total, 33 RCTs were included (N = 5421). The meta-analysis comparing IMIs to non-bonafide active controls yielded a significant standardized mean difference (SMD) of −0.36 (95%CI −0.53 to −0.19) favouring IMIs. Although meta-analytic pooling was not possible for the component and mediation studies, evidence suggests no differential effects regarding PTSD symptom reduction between different levels of support and personalization and between different types of exposure. Moreover, mediation studies revealed significant intervening variable effects for self-efficacy beliefs, perceived physical impairment, social acknowledgement, and trauma disclosure. Conclusions: Results indicate that IMIs for PTSD are superior to active controls. Furthermore, findings may contribute to the development of new interventions by outlining important directions for future research (e.g. regarding requirements for process research) and highlighting potential mechanisms of change (i.e. self-efficacy, perceived physical impairment, social acknowledgement, and trauma disclosure)

Intervention components, mediators, and mechanisms of change of internet- and mobile-based interventions for post-traumatic stress disorder: protocol for a systematic review and meta-analysis

Background While Internet- and mobile-based interventions (IMIs) might possess the potential to increase access to evidence-based therapies for post-traumatic stress disorder (PTSD), comprehensive knowledge on active intervention components and change mechanisms underlying their efficacy is largely pending so far. The proposed systematic review and meta-analysis will systematically review the current status of research on the efficacy of IMIs for adult PTSD compared to active control conditions and identify active intervention components and mediators responsible for therapeutic change. Methods A systematic literature search (PsycINFO, Medline/PubMed, Embase, CENTRAL, ICTRP, and Web of Science) will be conducted using keywords targeting “PTSD” and “Internet- and mobile-based interventions”. Two independent researchers will retrieve studies eligible for inclusion and extract and evaluate data (design, population, outcomes, sample size, duration of intervention and follow-up, drop-out rate). Risk of bias will be assessed, and results will be synthesized qualitatively and evaluated meta-analytically when possible. Discussion The results of this systematic review and meta-analysis might further contribute to the development of IMIs for PTSD by highlighting intervention components and mediators associated with their efficacy. Knowledge about the active ingredients might ultimately lead to more effective interventions and treatment packages, with implications for clinical practice and dissemination of these rather novel interventions. Systematic review registration PROSPERO (CRD42019130314)

More Light? Opportunities and Pitfalls in Digitalized Psychotherapy Process Research

While the evidence on the effectiveness of different psychotherapies is often strong, it is not settled whereby and how these therapies work. Knowledge on the causal factors and change mechanisms is of high clinical and public relevance, as it contributes to the empirically informed advancement of psychotherapeutic interventions. Here, digitalized research approaches might possess the potential to generate new insights into human behavior change, contributing to augmented interventions and mental healthcare practices with better treatment outcomes. In this perspective article, we describe recent findings of research into change mechanisms that were only feasible with digital tools and outline important future directions for this rather novel branch of research. Furthermore, we indicate several challenges and pitfalls that are to be solved, in order to advance digitalized psychotherapy process research, both methodologically and technologically

Can You Sleep? – Effect of Retrospective Recall of Child Maltreatment on Sleep Parameters and the Mediating Role of Psychological Distress Among Students of Two German Universities

Purpose: Child maltreatment may be linked with long-term sleeping disorders and limited coping with stress. Yet, the potential relationships are only marginally studied. Patients and Methods: Based on a sample of young adults (n = 312) this study aims at exploring the effects of child maltreatment and the experience of threat to personal safety and life in childhood on sleep disturbances in early adulthood. Data were collected at the two study sites, Ulm University and Bielefeld University, by an online survey. For both risk factors, child maltreatment and the experience of threat to personal safety and life in childhood, a direct impact on sleep disturbances and an indirect path via psychological distress were tested using Structural Equation Modelling (SEM). Results: In these models, the direct path to sleep disturbances turned out to be significant for the experience of threat to personal safety and life (Path C: b = 0.18, p = 0.013), but not for child maltreatment (Path C: b = 0.05, p = 0.491). However, the current level of psychological distress was found to have a mediating effect on sleep disturbances for both risk factors, thereby confirming indirect significant effects. Conclusion: Considering that the etiological pathway of child maltreatment on sleeping disturbances is mediated via psychological distress, this provides a venue to test in future research whether stress reduction interventions can reduce the negative consequences of child maltreatment on sleep disorders