Review
doi: 10.1192/bjp.2025.56.
Online ahead of print.
Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators
Mathias Harrer
1
, Antonia A Sprenger
2
, Susan Illing
3
, Marcel C Adriaanse
4
, Steven M Albert
5
, Esther Allart
6
, Osvaldo P Almeida
7
8
, Julian Basanovic
9
10
, Kim M P van Bastelaar
11
, Philip J Batterham
12
, Harald Baumeister
13
, Thomas Berger
14
, Vanessa Blanco
15
, Ragnhild Bø
16
, Robin J Casten
17
, Dicken Chan
18
, Helen Christensen
19
, Marketa Ciharova
20
, Lorna Cook
21
, John Cornell
22
, Elysia P Davis
23
, Keith S Dobson
24
, Elsien Dozeman
25
, Simon Gilbody
26
, Benjamin L Hankin
27
, Rimke Haringsma
28
, Kristof Hoorelbeke
29
, Michael R Irwin
30
31
, Femke Jansen
32
, Rune Jonassen
33
, Eirini Karyotaki
20
, Norito Kawakami
34
, J Philipp Klein
35
36
, Candace Konnert
24
, Kotaro Imamura
34
, Nils Inge Landrø
16
, María Asunción Lara
37
, Huynh-Nhu Le
38
, Dirk Lehr
39
, Juan V Luciano
40
41
, Steffen Moritz
42
, Jana M Mossey
43
, Ricardo F Muñoz
44
45
, Anna Muntingh
46
47
48
, Stephanie Nobis
49
, Richard Olmstead
31
30
, Patricia Otero
50
, Mirjana Pibernik-Okanović
51
, Anne Margriet Pot
52
, Charles F Reynolds 3rd
53
, Barry W Rovner
17
, Juan P Sanabria-Mazo
54
, Lasse B Sander
55
, Filip Smit
56
57
, Frank J Snoek
58
, Viola Spek
59
, Philip Spinhoven
60
, Liza Stelmach
61
, Yannik Terhorst
62
63
, Fernando L Vázquez
64
, Irma Verdonck-de Leeuw
65
32
, Ed Watkins
66
, Wenhui Yang
67
, Samuel Yeung Shan Wong
68
, Johannes Zimmermann
69
, Masatsugu Sakata
70
71
, Toshi A Furukawa
72
, Stefan Leucht
3
, Pim Cuijpers
20
, Claudia Buntrock #
2
, David Daniel Ebert #
73
Affiliations
Affiliations
- 1 Section for Evidence-Based Medicine in Psychiatry and Psychotherapy, Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany; and Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 2 Institute of Social Medicine and Health Systems Research, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
- 3 Section for Evidence-Based Medicine in Psychiatry and Psychotherapy, Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany.
- 4 Department of Health Sciences and Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 5 Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
- 6 Allart Supervisie, Nijmegen, The Netherlands.
- 7 Medical School, University of Western Australia, Western Australia, Australia.
- 8 Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia.
- 9 Department of Psychology, University of Exeter, Exeter, UK.
- 10 School of Psychological Science, University of Western Australia, Western Australia, Australia.
- 11 Amsterdam University Medical Centre, Amsterdam, The Netherlands.
- 12 Centre for Mental Health Research, College of Health and Medicine, The Australian National University, Canberra, Australian Capital Territory, Australia.
- 13 Department of Clinical Psychology and Psychotherapy, Ulm University, Ulm, Germany.
- 14 Institute of Psychology, University of Bern, Bern, Switzerland.
- 15 Department of Evolutionary and Educational Psychology, University of Santiago de Compostela, Santiago de Compostela, Spain.
- 16 Department of Psychology, University of Oslo, Oslo, Norway.
- 17 Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
- 18 School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.
- 19 Black Dog Institute, Sydney, New South Wales, Australia and School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
- 20 Department of Clinical, Neuro- and Developmental Psychology, WHO Collaborating Centre for Research and Dissemination of Psychological Interventions, Amsterdam Public Health Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 21 SMART Lab, Mood Disorders Centre, Department of Psychology, University of Exeter, Exeter, UK.
- 22 UT School of Public Health, University of Texas at San Antonio, San Antonio, TX, USA.
- 23 Department of Psychology, University of Denver, Denver, CO, USA.
- 24 Department of Psychology, University of Calgary, Calgary, Alberta, Canada.
- 25 GGZ inGeest, Specialized Mental Health Care, Amsterdam, The Netherlands.
- 26 York Mental Health & Addictions Research Group (MHARG), University of York, York, UK.
- 27 Department of Psychology, University of Illinois Urbana-Champaign, Champaign, IL, USA.
- 28 Division of Clinical and Health Psychology, Faculty of Social and Behavioral Sciences, Leiden University, Leiden, The Netherlands.
- 29 Department of Experimental Clinical and Health Psychology, University of Ghent, Ghent, Belgium.
- 30 Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
- 31 Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
- 32 Department of Otolaryngology-Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 33 Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
- 34 Department of Digital Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- 35 Department of Psychiatry, Psychosomatics and Psychotherapy, University of Lübeck, Lübeck, Germany.
- 36 Centre for Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany.
- 37 Dirección de Investigaciones Epidemiológicas y Psicosociales, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México, Mexico.
- 38 Department of Psychological and Brain Sciences, George Washington University, Washington, DC, USA.
- 39 Department of Health Psychology and Applied Biological Psychology, Institute of Psychology, Leuphana University Lueneburg, Lueneburg, Germany.
- 40 Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 41 Parc Sanitari Sant Joan de Déu, St Boi de Llobregat, Spain; and CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
- 42 Department of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
- 43 Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA, USA.
- 44 Department of Psychology, Palo Alto University, Palo Alto, CA, USA.
- 45 Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
- 46 Department for Anxiety and Depression, GGZ inGeest Mental Health Care, Amsterdam, The Netherlands.
- 47 Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 48 Mental Health Programme, Amsterdam Public Health, Amsterdam, The Netherlands.
- 49 Klinikum Osnabrück, Osnabrück, Germany.
- 50 Department of Psychology, University of La Coruña, La Coruña, Spain.
- 51 Vuk Vrhovac University Clinic for Diabetes, Merkur University Hospital, Zagreb, Croatia.
- 52 Erasmus School of Health Policy and Management, Erasmus University of Rotterdam, Rotterdam, The Netherlands.
- 53 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- 54 Parc Sanitari Sant Joan de Déu, St. Boi de Llobregat, Spain; and CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
- 55 Medical Psychology and Medical Sociology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
- 56 Department of Mental Health and Prevention, Trimbos Institute, Utrecht, The Netherlands.
- 57 Department of Epidemiology and Biostatistics, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
- 58 Amsterdam University Medical Centres, Amsterdam Public Health, Amsterdam, The Netherlands.
- 59 Fontys University of Applied Sciences, Eindhoven, The Netherlands.
- 60 Department of Clinical Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands.
- 61 Carewest, Calgary, Alberta, Canada.
- 62 Department of Psychology, Ludwig Maximilian University of Munich, Munich, Germany.
- 63 German Centre for Mental Health (DZPG), Partner-Site Munich-Augsburg, Munich, Germany.
- 64 Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Santiago de Compostela, Spain.
- 65 Department of Clinical, Neuro and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 66 SMART Lab, Mood Disorders Centre, School of Psychology, University of Exeter, Exeter, UK.
- 67 Department of Psychology, Hunan Normal University, Changsha, China.
- 68 Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- 69 Department of Psychology, University of Kassel, Kassel, Germany.
- 70 Department of Neurodevelopmental Disorders, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
- 71 Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
- 72 Kyoto University Office of Institutional Advancement and Communications, Kyoto, Japan.
- 73 Psychology and Digital Mental Health Care, School of Medicine and Health, Technical University of Munich, Munich, Germany.
# Contributed equally.
- PMID: 40365980
- DOI: 10.1192/bjp.2025.56
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Review
Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators
Mathias Harrer et al.
Br J Psychiatry.
.
Free article
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doi: 10.1192/bjp.2025.56.
Online ahead of print.
Authors
Mathias Harrer
1
, Antonia A Sprenger
2
, Susan Illing
3
, Marcel C Adriaanse
4
, Steven M Albert
5
, Esther Allart
6
, Osvaldo P Almeida
7
8
, Julian Basanovic
9
10
, Kim M P van Bastelaar
11
, Philip J Batterham
12
, Harald Baumeister
13
, Thomas Berger
14
, Vanessa Blanco
15
, Ragnhild Bø
16
, Robin J Casten
17
, Dicken Chan
18
, Helen Christensen
19
, Marketa Ciharova
20
, Lorna Cook
21
, John Cornell
22
, Elysia P Davis
23
, Keith S Dobson
24
, Elsien Dozeman
25
, Simon Gilbody
26
, Benjamin L Hankin
27
, Rimke Haringsma
28
, Kristof Hoorelbeke
29
, Michael R Irwin
30
31
, Femke Jansen
32
, Rune Jonassen
33
, Eirini Karyotaki
20
, Norito Kawakami
34
, J Philipp Klein
35
36
, Candace Konnert
24
, Kotaro Imamura
34
, Nils Inge Landrø
16
, María Asunción Lara
37
, Huynh-Nhu Le
38
, Dirk Lehr
39
, Juan V Luciano
40
41
, Steffen Moritz
42
, Jana M Mossey
43
, Ricardo F Muñoz
44
45
, Anna Muntingh
46
47
48
, Stephanie Nobis
49
, Richard Olmstead
31
30
, Patricia Otero
50
, Mirjana Pibernik-Okanović
51
, Anne Margriet Pot
52
, Charles F Reynolds 3rd
53
, Barry W Rovner
17
, Juan P Sanabria-Mazo
54
, Lasse B Sander
55
, Filip Smit
56
57
, Frank J Snoek
58
, Viola Spek
59
, Philip Spinhoven
60
, Liza Stelmach
61
, Yannik Terhorst
62
63
, Fernando L Vázquez
64
, Irma Verdonck-de Leeuw
65
32
, Ed Watkins
66
, Wenhui Yang
67
, Samuel Yeung Shan Wong
68
, Johannes Zimmermann
69
, Masatsugu Sakata
70
71
, Toshi A Furukawa
72
, Stefan Leucht
3
, Pim Cuijpers
20
, Claudia Buntrock #
2
, David Daniel Ebert #
73
Affiliations
- 1 Section for Evidence-Based Medicine in Psychiatry and Psychotherapy, Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany; and Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 2 Institute of Social Medicine and Health Systems Research, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
- 3 Section for Evidence-Based Medicine in Psychiatry and Psychotherapy, Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany.
- 4 Department of Health Sciences and Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 5 Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
- 6 Allart Supervisie, Nijmegen, The Netherlands.
- 7 Medical School, University of Western Australia, Western Australia, Australia.
- 8 Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia.
- 9 Department of Psychology, University of Exeter, Exeter, UK.
- 10 School of Psychological Science, University of Western Australia, Western Australia, Australia.
- 11 Amsterdam University Medical Centre, Amsterdam, The Netherlands.
- 12 Centre for Mental Health Research, College of Health and Medicine, The Australian National University, Canberra, Australian Capital Territory, Australia.
- 13 Department of Clinical Psychology and Psychotherapy, Ulm University, Ulm, Germany.
- 14 Institute of Psychology, University of Bern, Bern, Switzerland.
- 15 Department of Evolutionary and Educational Psychology, University of Santiago de Compostela, Santiago de Compostela, Spain.
- 16 Department of Psychology, University of Oslo, Oslo, Norway.
- 17 Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
- 18 School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.
- 19 Black Dog Institute, Sydney, New South Wales, Australia and School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
- 20 Department of Clinical, Neuro- and Developmental Psychology, WHO Collaborating Centre for Research and Dissemination of Psychological Interventions, Amsterdam Public Health Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 21 SMART Lab, Mood Disorders Centre, Department of Psychology, University of Exeter, Exeter, UK.
- 22 UT School of Public Health, University of Texas at San Antonio, San Antonio, TX, USA.
- 23 Department of Psychology, University of Denver, Denver, CO, USA.
- 24 Department of Psychology, University of Calgary, Calgary, Alberta, Canada.
- 25 GGZ inGeest, Specialized Mental Health Care, Amsterdam, The Netherlands.
- 26 York Mental Health & Addictions Research Group (MHARG), University of York, York, UK.
- 27 Department of Psychology, University of Illinois Urbana-Champaign, Champaign, IL, USA.
- 28 Division of Clinical and Health Psychology, Faculty of Social and Behavioral Sciences, Leiden University, Leiden, The Netherlands.
- 29 Department of Experimental Clinical and Health Psychology, University of Ghent, Ghent, Belgium.
- 30 Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
- 31 Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
- 32 Department of Otolaryngology-Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 33 Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
- 34 Department of Digital Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- 35 Department of Psychiatry, Psychosomatics and Psychotherapy, University of Lübeck, Lübeck, Germany.
- 36 Centre for Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany.
- 37 Dirección de Investigaciones Epidemiológicas y Psicosociales, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México, Mexico.
- 38 Department of Psychological and Brain Sciences, George Washington University, Washington, DC, USA.
- 39 Department of Health Psychology and Applied Biological Psychology, Institute of Psychology, Leuphana University Lueneburg, Lueneburg, Germany.
- 40 Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 41 Parc Sanitari Sant Joan de Déu, St Boi de Llobregat, Spain; and CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
- 42 Department of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
- 43 Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA, USA.
- 44 Department of Psychology, Palo Alto University, Palo Alto, CA, USA.
- 45 Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
- 46 Department for Anxiety and Depression, GGZ inGeest Mental Health Care, Amsterdam, The Netherlands.
- 47 Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 48 Mental Health Programme, Amsterdam Public Health, Amsterdam, The Netherlands.
- 49 Klinikum Osnabrück, Osnabrück, Germany.
- 50 Department of Psychology, University of La Coruña, La Coruña, Spain.
- 51 Vuk Vrhovac University Clinic for Diabetes, Merkur University Hospital, Zagreb, Croatia.
- 52 Erasmus School of Health Policy and Management, Erasmus University of Rotterdam, Rotterdam, The Netherlands.
- 53 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- 54 Parc Sanitari Sant Joan de Déu, St. Boi de Llobregat, Spain; and CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
- 55 Medical Psychology and Medical Sociology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
- 56 Department of Mental Health and Prevention, Trimbos Institute, Utrecht, The Netherlands.
- 57 Department of Epidemiology and Biostatistics, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
- 58 Amsterdam University Medical Centres, Amsterdam Public Health, Amsterdam, The Netherlands.
- 59 Fontys University of Applied Sciences, Eindhoven, The Netherlands.
- 60 Department of Clinical Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands.
- 61 Carewest, Calgary, Alberta, Canada.
- 62 Department of Psychology, Ludwig Maximilian University of Munich, Munich, Germany.
- 63 German Centre for Mental Health (DZPG), Partner-Site Munich-Augsburg, Munich, Germany.
- 64 Department of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Santiago de Compostela, Spain.
- 65 Department of Clinical, Neuro and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 66 SMART Lab, Mood Disorders Centre, School of Psychology, University of Exeter, Exeter, UK.
- 67 Department of Psychology, Hunan Normal University, Changsha, China.
- 68 Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- 69 Department of Psychology, University of Kassel, Kassel, Germany.
- 70 Department of Neurodevelopmental Disorders, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
- 71 Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
- 72 Kyoto University Office of Institutional Advancement and Communications, Kyoto, Japan.
- 73 Psychology and Digital Mental Health Care, School of Medicine and Health, Technical University of Munich, Munich, Germany.
# Contributed equally.
- PMID: 40365980
- DOI: 10.1192/bjp.2025.56
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Abstract
Background: It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims: To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method: Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment-covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results: IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = -0.48 to -0.27). Effects could not be ascertained up to 24 months (s.m.d. = -0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27-2.79), reliable improvement (relative risk = 1.38-3.17), deterioration (relative risk = 0.67-0.54) and close-to-symptom-free status (relative risk = 1.41-2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = -0.33 for PHQ-9 = 5).
Conclusions: Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Keywords: Meta-analysis; depressive disorders; precision medicine; prevention; psychological treatments.
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