Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators

Mathias Harrer; Antonia A. Sprenger; Susan Illing; Marcel C. Adriaanse; Steven M. Albert; Esther Allart; Osvaldo P. Almeida; Julian Basanovic; Kim M. P. van Bastelaar; Philip J. Batterham; Harald Baumeister; Thomas Berger; Vanessa Blanco; Ragnhild Bo; Robin J. Casten; Dicken Chan; Helen Christensen; Marketa Ciharova; Lorna Cook; John Cornell; Elysia P. Davis; Keith S. Dobson; Elsien Dozeman; Simon Gilbody; Benjamin L. Hankin; Rimke Haringsma; Kristof Hoorelbeke; Michael R. Irwin; Femke Jansen; Rune Jonassen; Eirini Karyotaki; Norito Kawakami; J. Philipp Klein; Candace Konnert; Kotaro Imamura; Nils Inge Landro; Maria Asuncion Lara; Huynh-Nhu Le; Dirk Lehr; Juan V. Luciano; Steffen Moritz; Jana M. Mossey; Ricardo F. Munoz; Anna Muntingh; Stephanie Nobis; Richard Olmstead; Patricia Otero; Mirjana Pibernik-Okanovic; Anne Margriet Pot; Charles F. Reynolds III; Barry W. Rovner; Juan P. Sanabria-Mazo; Lasse B. Sander; Filip Smit; Frank J. Snoek; Viola Spek; Philip Spinhoven; Liza Stelmach; Yannik Terhorst; Fernando L. Vazquez; Irma Verdonck-de Leeuw; Ed Watkins; Wenhui Yang; Samuel Yeung Shan Wong; Johannes Zimmermann; Masatsugu Sakata; Toshi A. Furukawa; Stefan Leucht; Pim Cuijpers; Claudia Buntrock; David Daniel Ebert

doi:10.1192/bjp.2025.56

Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators

Mathias Harrer, Antonia A. Sprenger, Susan Illing, Marcel C. Adriaanse, Steven M. Albert, Esther Allart, Osvaldo P. Almeida, Julian Basanovic, Kim M. P. van Bastelaar, Philip J. Batterham, Harald Baumeister, Thomas Berger, Vanessa Blanco, Ragnhild Bo, Robin J. Casten, Dicken Chan, Helen Christensen, Marketa Ciharova, Lorna Cook, John CornellElysia P. Davis, Keith S. Dobson, Elsien Dozeman, Simon Gilbody, Benjamin L. Hankin, Rimke Haringsma, Kristof Hoorelbeke, Michael R. Irwin, Femke Jansen, Rune Jonassen, Eirini Karyotaki, Norito Kawakami, J. Philipp Klein, Candace Konnert, Kotaro Imamura, Nils Inge Landro, Maria Asuncion Lara, Huynh-Nhu Le, Dirk Lehr, Juan V. Luciano, Steffen Moritz, Jana M. Mossey, Ricardo F. Munoz, Anna Muntingh, Stephanie Nobis, Richard Olmstead, Patricia Otero, Mirjana Pibernik-Okanovic, Anne Margriet Pot, Charles F. Reynolds III, Barry W. Rovner, Juan P. Sanabria-Mazo, Lasse B. Sander, Filip Smit, Frank J. Snoek, Viola Spek, Philip Spinhoven, Liza Stelmach, Yannik Terhorst, Fernando L. Vazquez, Irma Verdonck-de Leeuw, Ed Watkins, Wenhui Yang, Samuel Yeung Shan Wong, Johannes Zimmermann, Masatsugu Sakata, Toshi A. Furukawa, Stefan Leucht, Pim Cuijpers, Claudia Buntrock, David Daniel Ebert

Research output: Contribution to journal › Review article › peer-review

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.

Original language	English
Number of pages	14
Journal	British Journal of Psychiatry
DOIs	https://doi.org/10.1192/bjp.2025.56
Publication status	E-pub ahead of print - 14 May 2025

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Harrer, M., Sprenger, A. A., Illing, S., Adriaanse, M. C., Albert, S. M., Allart, E., Almeida, O. P., Basanovic, J., van Bastelaar, K. M. P., Batterham, P. J., Baumeister, H., Berger, T., Blanco, V., Bo, R., Casten, R. J., Chan, D., Christensen, H., Ciharova, M., Cook, L., ... Ebert, D. D. (2025). Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators. British Journal of Psychiatry. Advance online publication. https://doi.org/10.1192/bjp.2025.56

@article{89e202694f064c6a9283f5135ac677cd,

title = "Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators",

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",

author = "Mathias Harrer and Sprenger, {Antonia A.} and Susan Illing and Adriaanse, {Marcel C.} and Albert, {Steven M.} and Esther Allart and Almeida, {Osvaldo P.} and Julian Basanovic and {van Bastelaar}, {Kim M. P.} and Batterham, {Philip J.} and Harald Baumeister and Thomas Berger and Vanessa Blanco and Ragnhild Bo and Casten, {Robin J.} and Dicken Chan and Helen Christensen and Marketa Ciharova and Lorna Cook and John Cornell and Davis, {Elysia P.} and Dobson, {Keith S.} and Elsien Dozeman and Simon Gilbody and Hankin, {Benjamin L.} and Rimke Haringsma and Kristof Hoorelbeke and Irwin, {Michael R.} and Femke Jansen and Rune Jonassen and Eirini Karyotaki and Norito Kawakami and Klein, {J. Philipp} and Candace Konnert and Kotaro Imamura and Landro, {Nils Inge} and Lara, {Maria Asuncion} and Huynh-Nhu Le and Dirk Lehr and Luciano, {Juan V.} and Steffen Moritz and Mossey, {Jana M.} and Munoz, {Ricardo F.} and Anna Muntingh and Stephanie Nobis and Richard Olmstead and Patricia Otero and Mirjana Pibernik-Okanovic and Pot, {Anne Margriet} and {Reynolds III}, {Charles F.} and Rovner, {Barry W.} and Sanabria-Mazo, {Juan P.} and Sander, {Lasse B.} and Filip Smit and Snoek, {Frank J.} and Viola Spek and Philip Spinhoven and Liza Stelmach and Yannik Terhorst and Vazquez, {Fernando L.} and {Verdonck-de Leeuw}, Irma and Ed Watkins and Wenhui Yang and Wong, {Samuel Yeung Shan} and Johannes Zimmermann and Masatsugu Sakata and Furukawa, {Toshi A.} and Stefan Leucht and Pim Cuijpers and Claudia Buntrock and Ebert, {David Daniel}",

year = "2025",

month = may,

day = "14",

doi = "10.1192/bjp.2025.56",

language = "English",

journal = "British Journal of Psychiatry",

issn = "0007-1250",

publisher = "Cambridge University Press",

}

Harrer, M, Sprenger, AA, Illing, S, Adriaanse, MC, Albert, SM, Allart, E, Almeida, OP , Basanovic, J, van Bastelaar, KMP, Batterham, PJ, Baumeister, H, Berger, T, Blanco, V, Bo, R, Casten, RJ, Chan, D, Christensen, H, Ciharova, M, Cook, L, Cornell, J, Davis, EP, Dobson, KS, Dozeman, E, Gilbody, S, Hankin, BL, Haringsma, R, Hoorelbeke, K, Irwin, MR, Jansen, F, Jonassen, R, Karyotaki, E, Kawakami, N, Klein, JP, Konnert, C, Imamura, K, Landro, NI, Lara, MA, Le, H-N, Lehr, D, Luciano, JV, Moritz, S, Mossey, JM, Munoz, RF, Muntingh, A, Nobis, S, Olmstead, R, Otero, P, Pibernik-Okanovic, M, Pot, AM, Reynolds III, CF, Rovner, BW, Sanabria-Mazo, JP, Sander, LB, Smit, F, Snoek, FJ, Spek, V, Spinhoven, P, Stelmach, L, Terhorst, Y, Vazquez, FL, Verdonck-de Leeuw, I, Watkins, E, Yang, W, Wong, SYS, Zimmermann, J, Sakata, M, Furukawa, TA, Leucht, S, Cuijpers, P, Buntrock, C & Ebert, DD 2025, 'Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators', British Journal of Psychiatry. https://doi.org/10.1192/bjp.2025.56

TY - JOUR

T1 - Psychological intervention in individuals with subthreshold depression

T2 - individual participant data meta-analysis of treatment effects and moderators

AU - Harrer, Mathias

AU - Sprenger, Antonia A.

AU - Illing, Susan

AU - Adriaanse, Marcel C.

AU - Albert, Steven M.

AU - Allart, Esther

AU - Almeida, Osvaldo P.

AU - Basanovic, Julian

AU - van Bastelaar, Kim M. P.

AU - Batterham, Philip J.

AU - Baumeister, Harald

AU - Berger, Thomas

AU - Blanco, Vanessa

AU - Bo, Ragnhild

AU - Casten, Robin J.

AU - Chan, Dicken

AU - Christensen, Helen

AU - Ciharova, Marketa

AU - Cook, Lorna

AU - Cornell, John

AU - Davis, Elysia P.

AU - Dobson, Keith S.

AU - Dozeman, Elsien

AU - Gilbody, Simon

AU - Hankin, Benjamin L.

AU - Haringsma, Rimke

AU - Hoorelbeke, Kristof

AU - Irwin, Michael R.

AU - Jansen, Femke

AU - Jonassen, Rune

AU - Karyotaki, Eirini

AU - Kawakami, Norito

AU - Klein, J. Philipp

AU - Konnert, Candace

AU - Imamura, Kotaro

AU - Landro, Nils Inge

AU - Lara, Maria Asuncion

AU - Le, Huynh-Nhu

AU - Lehr, Dirk

AU - Luciano, Juan V.

AU - Moritz, Steffen

AU - Mossey, Jana M.

AU - Munoz, Ricardo F.

AU - Muntingh, Anna

AU - Nobis, Stephanie

AU - Olmstead, Richard

AU - Otero, Patricia

AU - Pibernik-Okanovic, Mirjana

AU - Pot, Anne Margriet

AU - Reynolds III, Charles F.

AU - Rovner, Barry W.

AU - Sanabria-Mazo, Juan P.

AU - Sander, Lasse B.

AU - Smit, Filip

AU - Snoek, Frank J.

AU - Spek, Viola

AU - Spinhoven, Philip

AU - Stelmach, Liza

AU - Terhorst, Yannik

AU - Vazquez, Fernando L.

AU - Verdonck-de Leeuw, Irma

AU - Watkins, Ed

AU - Yang, Wenhui

AU - Wong, Samuel Yeung Shan

AU - Zimmermann, Johannes

AU - Sakata, Masatsugu

AU - Furukawa, Toshi A.

AU - Leucht, Stefan

AU - Cuijpers, Pim

AU - Buntrock, Claudia

AU - Ebert, David Daniel

PY - 2025/5/14

Y1 - 2025/5/14

N2 - 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.

AB - 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.

KW - Meta-analysis

KW - Depressive disorders

KW - Precision medicine

KW - Prevention

KW - Psychological treatments

UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=uwapure5-25&SrcAuth=WosAPI&KeyUT=WOS:001487977800001&DestLinkType=FullRecord&DestApp=WOS_CPL

U2 - 10.1192/bjp.2025.56

DO - 10.1192/bjp.2025.56

M3 - Review article

C2 - 40365980

SN - 0007-1250

JO - British Journal of Psychiatry

JF - British Journal of Psychiatry

ER -

Psychological intervention in individuals with subthreshold depression: individual participant data meta-analysis of treatment effects and moderators

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