Mechanisms of change in psychotherapy for depression: An empirical update and evaluation of research aimed at identifying psychological mediators
Open accessAbstract
We present a systematic empirical update and critical evaluation of the current status of research aimed at identifying a variety of psychological mediators in various forms of psychotherapy for depression. We summarize study characteristics and results of 35 relevant studies, and discuss the extent to which these studies meet several important requirements for mechanism research. Our review indicates that in spite of increased attention for the topic, advances in theoretical consensus about necessities for mechanism research, and sophistication of study designs, research in this field is still heterogeneous and unsatisfactory in methodological respect. Probably the biggest challenge in the field is demonstrating the causal relation between change in the mediator and change in depressive symptoms. The field would benefit from a further refinement of research methods to identify processes of therapeutic change. Recommendations for future research are discussed. However, even in the most optimal research designs, explaining psychotherapeutic change remains a challenge. Psychotherapy is a multi-dimensional phenomenon that might work through interplay of multiple mechanisms at several levels. As a result, it might be too complex to be explained in relatively simple causal models of psychological change.
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Our results align with other recent reviews in calling for further investigation and greater methodological rigor in order to identify specific mediators leading to positive change in psychotherapy for adolescents.
“Despite multiple limitations, our results align with other recent reviews [28, 31, 33], in calling for further investigation and greater methodological rigor in order to identify specific mediators leading to positive change in psychotherapy for adolescents.”
From Mediators of outcome in adolescent psychotherapy and their implications for theories and mechanisms of change: a systematic review (2024) · cites this paper as [28]
The Discussion (page unavailable) calls for further research and more rigorous methods to identify mediators of change in psychotherapy for depression. The review includes studies of depressed adolescents, but its recommendations address depression psychotherapy broadly rather than psychotherapy for adolescents specifically. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPsychotherapy is a complex process involving multiple elements that most likely interact with one another, and simple causal models probably will not advance our understanding of how it works.
“Moreover, by definition, psychotherapy is a complex process involving multiple elements that most likely interact with one another, and simple causal models probably will not advance our understanding of how it works (Lemmens et al. 2016, Lorenzo-Luaces & DeRubeis 2018).”
From The Role of Common Factors in Psychotherapy Outcomes (2019) · cites this paper as Lemmens et al. 2016
The Discussion describes psychotherapy for depression as a complex process involving interacting mechanisms and says it might be too complex for relatively simple causal models to explain. The citing sentence broadens this from psychotherapy for depression to psychotherapy generally and states the limitation of simple models more firmly than the source does. (LLM, conf=0.83)
Experimental — accuracy not yet measuredFace-to-face and internet-based settings generally seem to share findings on relevant mechanisms of change.
“While the face-to-face and internetbased setting generally seem to share findings on relevant mechanisms of change (e.g., for depression: Domhardt etal., 2020; Lemmens etal., 2016)”
From Transdiagnostic Processes as Mediators of Change in an Internet-Delivered Intervention Based on the Unified Protocol (2022) · cites this paper as Lemmens et al., 2016
Section 3.2.1 reports findings on potential mediators in online CBT and problem-solving therapy for depression, while section 3.1 summarizes mediator findings across the review's psychotherapy studies. The paper does not compare internet-based with face-to-face settings or conclude that their findings generally align; it also cautions that the online study could not establish the temporal order needed to identify a mechanism of change. No page number was supplied in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredSeveral quality criteria of mediation studies outlined by Lemmens et al. (2016) could be established: an RCT with a control group, n > 40 per group, and assessment of several mediators.
“While several other of the quality criteria of mediation studies outlined by Lemmens etal. (2016) could be established”
From Transdiagnostic Processes as Mediators of Change in an Internet-Delivered Intervention Based on the Unified Protocol (2022) · cites this paper as Lemmens et al., 2016
Section 2.2 (Data assessment) lists an RCT design, a control group, sufficient sample size, and multiple potential mediators as criteria. It defines sufficient sample size as n ≥ 40, whereas the claim says n > 40 per group; section 3.2 discusses sample size per condition but does not resolve that threshold difference. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPsychotherapy is a multi-dimensional phenomenon that might work through interplay of multiple mechanisms at several levels, and as a result, it might be too complex to be explained in relatively simple causal models of psychological change.
“Psychotherapy is a multi‐dimensional phenomenon that might work through interplay of multiple mechanisms at several levels. As a result, it might be too complex to be explained in relatively simple causal models of psychological change (Lemmens et al. 2016).”
From Exploring Moderators and Mediators of the Outcome of Group Cognitive Behavioural Therapy Compared With Group Schema Therapy for Social Anxiety Disorder and Comorbid Avoidant Personality Disorder. (2025) · cites this paper as Lemmens et al. 2016
The Discussion says that psychotherapy for depression may involve interacting mechanisms at several levels and may be too complex for simple causal models of psychological change. The citing sentence closely paraphrases this point but omits the source’s restriction to depression, presenting it as a claim about psychotherapy generally. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Even in CBT the evidence base for mechanisms of change is inconclusive.
“However, even in CBT the evidence base is inconclusive”
From Mediators of outcome in adolescent psychotherapy and their implications for theories and mechanisms of change: a systematic review (2024) · cites this paper as [28]
Studies were independently and again in pairs checked for general criteria for identifying mediators of psychosocial interventions in research, such as summarized by Kazdin and Lemmens et al.
“Although no standard form for evaluating mediation studies has been established, studies were independently and again in pairs checked for general criteria for identifying mediators of psychosocial interventions in research, such as summarized by Kazdin [13] and Lemmens et al. [28].”
From Mediators of outcome in adolescent psychotherapy and their implications for theories and mechanisms of change: a systematic review (2024) · cites this paper as [28]
Lemmens et al. concluded that the evidence for the mediational role of various constructs is largely mixed and that better designed studies are urgently needed.
“Their conclusion is that the evidence for the mediational role of the various constructs (specific and nonspecific) is largely mixed and that better designed studies are urgently needed to understand the mechanisms of psychotherapy.”
From The Role of Common Factors in Psychotherapy Outcomes (2019) · cites this paper as Lemmens et al. 2016
The strongest support was found for changes in dysfunctional attitudes, negative automatic thoughts, rumination, worry, and the use of mindfulness skills, but about half of the studies did not detect a mediational role for the construct under investigation.
“The strongest support was found for changes in dysfunctional attitudes, negative automatic thoughts, rumination, worry, and the use of mindfulness skills, but it should also be noted that about half of the studies did not detect a mediational role for the construct under investigation.”
From The Role of Common Factors in Psychotherapy Outcomes (2019) · cites this paper as Lemmens et al. 2016
In total, 39 different potential mediators were investigated, mostly related to CBT and CBT processes.
“In total, 39 different potential mediators (i.e., therapeutic processes) were investigated, mostly related to CBT and CBT processes.”
From The Role of Common Factors in Psychotherapy Outcomes (2019) · cites this paper as Lemmens et al. 2016
The sample size of 147 meets Lemmens et al.'s proposed criterion of a sample size no less than 40 for tests of mediation.
“Furthermore, the sample size of 147 meets Lemmens et al.'s proposed criterion of a sample size no <40 for tests of mediation (Lemmens et al., 2016).”
From Efficacy and mechanisms of mobile application-delivered Acceptance and Commitment Therapy for posttraumatic stress disorder in China: Study protocol for a randomized controlled trial (2022) · cites this paper as Lemmens et al., 2016
The study fulfilled multiple criteria for mechanism research (Lemmens et al. 2016), by using a RCT design that included a comparison group, a sufficient sample size (n > 40), examining multiple potential mediators, and the assessment of temporality.
“Important strengths of this study were that it fulfilled multiple criteria for mechanism research (Lemmens et al. 2016), by using a RCT design that included a comparison group, a sufficient sample size (n > 40), examining multiple potential mediators, and the assessment of temporality.”
From Exploring Moderators and Mediators of the Outcome of Group Cognitive Behavioural Therapy Compared With Group Schema Therapy for Social Anxiety Disorder and Comorbid Avoidant Personality Disorder. (2025) · cites this paper as Lemmens et al. 2016
Criteria specificity, consistency, and gradient were not assessed because they are not meaningfully applicable in single studies or are too exclusive for some therapeutic processes.
“In accordance with prior research [24,44], criteria specificity, consistency, and gradient were not assessed, as they are not meaningfully applicable in single studies (consistency) or are too exclusive for some therapeutic processes (gradient and specificity).”
From Mechanisms of Change in Digital Health Interventions for Mental Disorders in Youth: Systematic Review (2021) · cites this paper as [44]
The rating system for process research quality was based on Kazdin's initial criteria to approach causality, modified by Domhardt et al and Lemmens et al.
“The rating system was based on Kazdin’s [25] initial criteria to approach causality, modified by Domhardt et al [24] and Lemmens et al [44].”
From Mechanisms of Change in Digital Health Interventions for Mental Disorders in Youth: Systematic Review (2021) · cites this paper as [44]
The review's findings seem to be in line with other research pointing to important methodological shortcomings of mediation studies.
“the findings of our review seem to be in line with those of other research [24,44,45,83], pointing to important methodological shortcomings of mediation studies”
From Mechanisms of Change in Digital Health Interventions for Mental Disorders in Youth: Systematic Review (2021) · cites this paper as [44]
Mediation studies with IMIs for depression exhibit a substantially larger amount of study participants on average (M = 262, SD = 243) compared to conventional psychotherapy process research for depression (M = 173, SD = 145).
“This assumption is corroborated in a recent review, showing that mediation studies with IMIs for depression (Domhardt et al., 2021) exhibit a substantial larger amount of study participants on average (M = 262, SD = 243), when compared to conventional psychotherapy process research for depression (Lemmens et al., 2016; M = 173, SD = 145).”
From More Light? Opportunities and Pitfalls in Digitalized Psychotherapy Process Research (2021) · cites this paper as Lemmens et al., 2016
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Domhardt, M., & Baumeister, H. (2021) · Psychotherapeut · doi:10.1007/s00278-021-00525-2 · Cited by 9 · see citing works
van Luenen, S., Kraaij, V., Spinhoven, P., Wilderjans, T., & Garnefski, N. (2019) · JMIR Mental Health · doi:10.2196/12711 · Cited by 10 · see citing works
Goger, P., Guo, R., Jo, S., Cha, C. B., Ribeiro, J. D., Huang, X., & Fox, K. R. (2024) · Behavior Therapy · doi:10.1016/j.beth.2024.10.003 · Cited by 9 · see citing works
Positive Affect Treatment for Depression, Anxiety, and Low Positive Affect
Meuret, A. E., Rosenfield, D., Wang, E., Hough, C. M., Ritz, T., & Craske, M. G. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.7403 · Cited by 9 · see citing works
Domhardt, M., Grund, S., Mayer, A., Büscher, R., Ebert, D. D., Sander, L., Karyotaki, E., Cuijpers, P. J., & Baumeister, H. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.899115 · Cited by 8 · see citing works
Categorizing treatment mechanisms for Complementary and Integrative Musculoskeletal Interventions
Cook, C. E., Abraira, V. E., Burns, J. W., Degenhardt, B. F., Kawchuk, G. N., Keter, D. L., Loghmani, M. T., Reed, W. R., Winkelstein, B. A., & McDevitt, A. W. (2025) · International journal of osteopathic medicine · doi:10.1016/j.ijosm.2025.100749 · Cited by 7 · see citing works
Redefining Therapeutic Outcomes of Depression Treatment
Slofstra, C., Booij, S. H., Hoenders, R. H. J., & Castelein, S. (2019) · Journal for Person-Oriented Research · doi:10.17505/jpor.2019.10 · Cited by 8 · see citing works
Camuso, J. A., & Rohan, K. J. (2020) · Cognitive Therapy and Research · doi:10.1007/s10608-020-10086-4 · Cited by 7 · see citing works
- Authors
- Lemmens, L. H. J. M., Müller, V. N. L. S., Arntz, A., & Huibers, M. J. H.
- Affiliations
- Maastricht University (NL)
- Universität Trier (DE)
- Corresponding author
- Lemmens, Lotte H.J.M.
- Venue
- Clinical Psychology Review
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 50
- Pages
- 95-107
- ISSN
- 0272-7358 (ISSN-L)
- OpenAlex
- W2523667356
- Cited by
- 211
- References
- 75
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 18 · 2023: 18 · 2022: 30 · 2021: 40 · 2020: 26 · 2019: 23 · 2018: 8 · 2017: 10
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Psychology Review (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Applied Psychology › Digital Mental Health Interventions
- Keywords
- psychotherapy for depression, mechanisms of change, psychological mediators, therapeutic change, causal inference, mediation analysis, methodological quality, depressive symptoms
- MeSH terms
- Depression, Depressive Disorder, Humans, Psychotherapy
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