The main findings for the intervention-level NMA reported in this chapter are reproduced or adapted from Caldwell et al.1 © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. The text below includes substantial additions and formatting changes to the original text, as well as changes to the reporting approach.
In this chapter, we report the systematic review and NMA results for studies reporting a depression outcome only.
Systematic review
Studies included in the review
The overall PRISMA flow diagram for the project can be seen in Figure 2. There were 105 studies reporting a self-reported depression outcome. The full list of included studies can be found in Appendix 2. Of these 105 studies, the primary focus of 62 studies was the prevention of depression, 29 focused on the prevention of anxiety and depression, and 14 focused on the prevention of anxiety alone. A subgroup analysis to explore whether or not intervention effects varied depending on intended intervention focus is reported subsequently in Exploring heterogeneity and small-study effects.
Study characteristics are reported in Appendix 2. Included studies were published between 1993 and 2018, and randomised between 16 and 8873 participants (median 198). Fifty-three studies were cluster randomised, of which seven reported cluster-adjusted means (SEs) and 29 reported results from appropriate models. The median number of clusters was 13 [interquartile range (IQR) 8–22 clusters]. Fifty-two were individually randomised trials. Ninety-seven studies reported a post-intervention end point, 64 reported a follow-up of between 6 and 12 months, and 18 reported a follow-up of between 13 and 24 months. Six reported a follow-up of ≥ 25 months.
Fifty-seven studies were classified as universal and 48 as targeted (38 indicated, 10 selective). Twenty studies were implemented in a primary school setting, 72 in secondary school, eight in tertiary education and five across multiple settings. A total of 94 studies were conducted in HICs, with 10 conducted in MICs and one in a LIC. Of the studies conducted in HICs, seven were conducted in lower-income settings, as specified by the trial authors.
Risk-of-bias assessment
Study-level risk-of-bias assessments are reported in Appendix 2. Seventeen of the 105 studies reporting a depression outcome were assessed as being at low risk of bias for both random sequence generation and allocation concealment. A further 21 studies reported a suitable randomisation approach, but did not report sufficient details of allocation concealment to allow assessment. Seven studies were judged as being at low risk of bias for participant blinding; all were active, or attention controlled. Study protocols and/or trial registrations were available for 27 studies, of which 25 were judged to be at low risk of bias for selective outcome reporting. Two studies were judged as being at unclear risk of bias. One reported a trial registration number that we could not locate, and the primary outcome was not clear for the other. For cluster randomised trials, we also considered how recruitment, randomisation and analysis were conducted under the Cochrane Risk of Bias tool heading of ‘other bias’. Of 53 cluster RCTs, 18 were judged to be at high risk and 16 at unclear risk of ‘other bias’.
Interventions and components identified in the review
Table 6 reports the interventions and components identified for studies reporting a self-reported depression outcome. Twenty-three studies were multiarm, comparing three or more interventions. Seventy-six studies included an intervention based on CBT, five studies included an intervention based on a combination of CBT + IPT and four were based on IPT alone. Four studies included a relaxation/mindfulness-based intervention, six included a third-wave intervention, four included a behavioural intervention, two included an exercise intervention and one used a CBM approach. One study used an occupational therapy-based intervention. With regard to non-active comparators, 26 studies were waiting list controlled, 33 were usual curriculum controlled, 27 had a no-intervention control and nine used an attention control. Two studies were classified as having a psychoeducation control group and six were classified as having a psychosupport control.
| Study | Focusa | Classification | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention level | Component level for active intervention only | |||||||||||||
| Armb 1 | Armb 2 | Armb 3 | Armb 4 | Psychoeducation | Cognitive | Behavioural | Mindfulness | Third wave | Relaxation | Physiological | Exercise | Bias modification | ||
| Universal secondary | ||||||||||||||
| Araya et al.118 2013 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Aune and Stiles119 2009 | Anxiety | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Barrett et al.121 2005 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Barry et al.190 2017 | Depression | (Usual curriculum) | CBT | + | + | – | – | – | – | – | – | – | ||
| Bonhauser et al.122 2005 | Anxiety + depression | Exercise | Exercise | – | – | – | – | – | – | – | + | – | ||
| Bonhauser et al.122 2005 | – | – | – | – | – | – | – | + | – | |||||
| Burckhardt et al.124 2015 | Anxiety + depression | (Attention control) | Mindfulness/relaxation | – | – | – | + | – | + | – | – | – | ||
| Burckhardt et al.191 2016 | Anxiety + depression | (Usual curriculum) | Third wave | + | – | + | + | + | + | – | – | – | ||
| Calear et al.125 2009 | Anxiety + depression | (Waiting list) | CBT | – | + | + | – | – | + | – | – | – | ||
| Calear et al.126 2016 | Anxiety | (Waiting list) | CBT | CBT | + | + | + | + | – | + | – | – | – | |
| Calear et al.126 2016 | Anxiety | + | + | + | + | – | + | – | – | – | ||||
| Calear et al.127 2016 | Anxiety | (Waiting list) | CBT | + | + | + | + | – | + | – | – | – | ||
| Chaplin et al.192 2006 | Depression | (No intervention) | CBT | CBT | – | + | + | – | – | + | – | – | – | |
| Chaplin et al.192 2006 | Depression | – | + | + | – | – | + | – | – | – | ||||
| Clarke et al.193 1993 | Depression | (Usual curriculum) | Psychoeducation | + | – | – | – | – | – | – | – | – | ||
| Clarke et al.193 1993 | Depression | (Usual curriculum) | Behavioural therapy | + | – | + | – | – | – | – | – | – | ||
| Gillham et al.128 2006 | Anxiety + depression | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Gillham et al.194 2007 | Depression | (No intervention) | (Attention control) | CBT | – | + | + | – | – | + | – | – | – | |
| Gucht et al.129 2017 | Anxiety + depression | (Usual curriculum) | Third wave | + | – | – | – | + | – | – | – | – | ||
| Hodas131 2016 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Horowitz et al.195 2007 | Depression | (Usual curriculum) | CBT | IPT | + | + | + | – | – | – | – | – | – | |
| Horowitz et al.195 2007 | Depression | + | – | + | – | – | – | – | – | – | ||||
| Johnson et al.132 2016 | Anxiety + depression | (Usual curriculum) | Third wave | – | – | – | + | + | + | – | – | – | ||
| Johnson et al.133 2017 | Anxiety + depression | (Usual curriculum) | Third wave | Third wave | – | – | – | + | + | + | – | – | – | |
| Johnson et al.133 2017 | Anxiety + depression | – | – | – | + | + | + | – | – | – | ||||
| Kindt et al.196 2014 | Depression | (Usual curriculum) | CBT | + | + | + | – | – | + | – | – | – | ||
| Lock and Barrett134 2003 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Lowry-Webster et al.135 2001 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Merry et al.197 2004 | Depression | (Attention control) | CBT + IPT | – | + | + | – | – | + | – | – | – | ||
| Perry et al.136 2017 | Depression | (Attention control) | CBT | + | + | + | – | – | + | – | – | – | ||
| Pössel et al.198 2004 | Depression | (Usual curriculum) | CBT | + | + | + | – | – | – | – | – | – | ||
| Pössel et al.199 2011 | Depression | (Usual curriculum) | CBT | + | + | + | – | – | – | – | – | – | ||
| Pössel et al.200 2013 | Depression | (Usual curriculum) | (Attention control) | CBT | + | + | + | – | – | – | – | – | – | |
| Raes et al.201 2014 | Depression | (Usual curriculum) | Third wave | + | – | – | + | + | + | – | – | – | ||
| Rivet-Duval et al.202 2011 | Depression | (Waiting list) | CBT + IPT | – | + | + | – | – | + | – | – | – | ||
| Roberts et al.138 2003 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Roberts et al.139 2010 | Anxiety + depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Rose et al.203 2014 | Depression | (Attention control) | CBT + IPT | CBT + IPT | – | + | + | – | – | + | – | – | – | |
| Rose et al.203 2014 | Depression | – | + | + | – | – | + | – | – | – | ||||
| Sawyer et al.204 2010 | Depression | (Usual curriculum) | CBT | + | + | + | – | – | + | – | – | – | ||
| Shatté205 1997 | Depression | (No intervention) | (Attention control) | CBT | – | + | + | – | – | – | – | – | – | |
| Sheffield et al.141 2006 | Depression | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Spence et al.206 2003 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Stallard et al.142 2013 | Depression | (Usual curriculum) | (Attention control) | CBT + IPT | + | + | + | – | – | + | – | – | – | |
| Tak et al.207 2016 | Depression | (Usual curriculum) | CBT | + | + | + | – | – | – | – | – | – | ||
| Tomba et al.143 2010 | Anxiety + depression | CBT | CBT | + | + | + | – | – | + | – | – | – | ||
| Tomba et al.143 2010 | + | + | + | – | – | + | – | – | – | |||||
| Wong et al.144 2014 | Anxiety + depression | (Usual curriculum) | CBT | CBT | + | + | + | – | – | – | – | – | – | |
| Wong et al.144 2014 | Anxiety + depression | + | + | + | – | – | – | – | – | – | ||||
| Universal primary | ||||||||||||||
| Ahlen et al.145 2018 | Anxiety + depression | (Usual curriculum) | CBT | + | + | + | – | – | + | – | – | – | ||
| Barrett and Turner147 2001 | Anxiety | (Usual curriculum) | CBT | CBT | + | + | + | – | – | + | – | – | – | |
| Barrett and Turner147 2001 | Anxiety | + | + | + | – | – | + | – | – | – | ||||
| Cardemil et al.208 2007 | Depression | (Usual curriculum) | CBT | + | + | + | – | – | – | – | – | – | ||
| Essau et al.150 2012 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Gallegos151 2008 | Anxiety + depression | (Usual curriculum) | CBT | + | + | + | – | – | + | – | – | – | ||
| Gillham209 1994 | Depression | (No intervention) | CBT | CBT | – | + | + | – | – | + | – | – | – | |
| Gillham209 1994 | – | + | + | – | – | + | – | – | – | |||||
| Johnstone et al.152 2014 | Anxiety + depression | (Usual curriculum) | CBT | – | + | + | – | – | + | – | – | – | ||
| Mendelson et al.210 2010 | Depression | (Waiting list) | Mindfulness/relaxation | – | – | – | + | – | + | – | – | – | ||
| Pattison and Lynd-Stevenson155 2001 | Depression | (No intervention) | (Attention control) | CBT | CBT | – | + | + | – | – | – | – | – | – |
| Pattison and Lynd-Stevenson155 2001 | Depression | – | + | + | – | – | – | – | – | – | ||||
| Pophillat et al.156 2016 | Anxiety + depression | (Usual curriculum) | CBT | + | + | + | – | – | + | – | – | – | ||
| Quayle et al.211 2001 | Depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Rooney et al.157 2006 | Depression | (No intervention) | CBT | – | + | + | – | – | + | – | – | – | ||
| Soffer212 2003 | Depression | (No intervention) | (Attention control) | Behavioural therapy | – | – | + | – | – | – | – | – | – | |
| Stallard et al.159 2014 | Anxiety | (Usual curriculum) | CBT | CBT | + | + | + | – | – | + | – | – | – | |
| Stallard et al.159 2014 | Anxiety | + | + | + | – | – | + | – | – | – | ||||
| Targeted secondary | ||||||||||||||
| Arnarson and Craighead213 2009 | Depression | (Waiting list) | CBT + IPT | – | + | + | – | – | + | – | – | – | ||
| Balle and Tortella-Feliu160 2010 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Berry and Hunt161 2009 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Clarke et al.214 1995 | Depression | (No intervention) | CBT | – | + | – | – | – | – | – | – | – | ||
| Congleton215 1995 | Depression | (Waiting list) | CBT | + | + | – | – | – | – | – | – | – | ||
| Cova et al.162 2011 | Depression | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Dobson et al.163 2010 | Anxiety + depression | (Attention control) | CBT | – | + | + | – | – | – | – | – | – | ||
| Fitzgerald et al.114 2016 | Anxiety | (Attention control) | CBM | – | – | – | – | – | – | – | – | + | ||
| Fung et al.216 2016 | Anxiety + depression | (Waiting list) | Mindfulness/relaxation | – | – | – | + | – | + | – | – | – | ||
| Gaete et al.164 2016 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Gillham et al.165 2012 | Depression | (No intervention) | CBT | CBT | + | + | + | – | – | + | – | – | – | |
| Gillham et al.165 2012 | Depression | + | + | + | – | – | + | – | – | – | ||||
| Hunt et al.166 2009 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Jordans et al.167 2010 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Livheim et al.217 2015 | Depression | Psychosupport | Third wave | – | – | – | – | + | – | – | – | – | ||
| McCarty et al.218 2011 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | + | – | – | – | ||
| McCarty et al.219 2013 | Depression | Psychosupport | CBT | – | + | + | – | – | + | – | – | – | ||
| Noël et al.220 2013 | Depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Peng et al.170 2015 | Anxiety + depression | (No intervention) | Exercise | – | – | – | – | – | + | – | + | – | ||
| Poppelaars et al.221 2016 | Depression | (Waiting list) | CBT | CBT | CBT | + | + | – | – | – | – | – | – | – |
| Poppelaars et al.221 2016 | Depression | – | + | + | – | – | – | – | – | – | ||||
| Poppelaars et al.221 2016 | Depression | + | + | + | – | – | – | – | – | – | ||||
| Puskar et al.222 2003 | Depression | (No intervention) | CBT | – | + | + | – | – | + | – | – | – | ||
| Rohde et al.223 2014 | Depression | Psychoeducation | CBT | CBT | – | + | + | – | – | – | – | – | – | |
| Rohde et al.223 2014 | Depression | – | + | + | – | – | – | – | – | – | ||||
| Sheffield et al.141 2006 | Depression | (No intervention) | CBT | CBT | CBT | + | + | + | – | – | – | – | – | – |
| Sheffield et al.141 2006 | Depression | + | + | + | – | – | – | – | – | – | ||||
| Sheffield et al.141 2006 | Depression | + | + | + | – | – | – | – | – | – | ||||
| Stallard et al.142 2013 | Depression | (Usual curriculum) | (Attention control) | CBT + IPT | + | + | + | – | – | + | – | – | – | |
| Stice et al.224 2008 | Depression | Psychoeducation | Psychosupport | CBT | CBT | – | + | + | – | – | – | – | – | – |
| Stice et al.224 2008 | Depression | + | – | + | – | – | – | – | – | – | ||||
| Stoppelbein225 2003 | Depression | (Attention control) | CBT | + | + | + | – | – | + | – | – | – | ||
| Topper et al.173 2017 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Wijnhoven et al.226 2014 | Depression | (Waiting list) | CBT | – | + | – | – | – | – | – | – | – | ||
| Woods and Jose227 2011 | Depression | (Usual curriculum) | CBT | + | + | + | – | – | – | – | – | – | ||
| Young et al.228 2006 | Depression | Psychosupport | IPT | + | – | + | – | – | – | – | – | – | ||
| Young et al.229 2010 | Depression | Psychosupport | IPT | + | – | + | – | – | – | – | – | – | ||
| Young et al.230 2016 | Depression | Psychosupport | IPT | + | – | + | – | – | – | – | – | – | ||
| Targeted primary | ||||||||||||||
| Cowell et al.231 2009 | Depression | (No intervention) | Psychosupport | – | – | – | – | – | – | – | – | – | ||
| Jaycox et al.232 1994 | Depression | (Waiting list) | CBT | – | + | + | – | – | + | – | – | – | ||
| Manassis et al.175 2010 | Anxiety + depression | (Attention control) | CBT | + | + | – | – | – | – | – | – | – | ||
| Simpson179 2008 | Anxiety + depression | (Attention control) | CBT | + | + | + | – | – | – | – | – | – | ||
| Siu180 2007 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Tokolahi et al.181 2018 | Anxiety + depression | (Waiting list) | Occupational therapy | – | – | – | – | – | – | – | – | – | ||
| Universal tertiary/university setting | ||||||||||||||
| Reynolds et al.233 2011 | Depression | (Usual curriculum) | Behavioural therapy | – | – | + | – | – | – | – | – | – | ||
| Targeted tertiary/university setting | ||||||||||||||
| Cui et al.183 2016 | Depression | (Waiting list) | Psychosupport | CBT | + | + | + | – | – | + | – | – | – | |
| Ellis et al.184 2011 | Depression | (No intervention) | Psychosupport | CBT | + | + | + | – | – | + | – | – | – | |
| Higgins185 2007 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Peden et al.234 2000 | Depression | (No intervention) | CBT | – | + | – | – | – | – | – | – | – | ||
| Seligman et al.186 1999 | Anxiety + depression | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Seligman et al.187 2007 | Anxiety + depression | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Takagaki et al.235 2016 | Depression | (No intervention) | Behavioural therapy | + | – | + | – | – | – | – | – | – | ||
| Multiple/mixed settings | ||||||||||||||
| Liddle and Macmillan188 2010 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| McLaughlin236 2011 | Depression | Psychosupport | CBT | – | + | + | – | – | + | – | – | – | ||
| Stice et al.237 2007 | Depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Velásquez et al.189 2015 | Anxiety + depression | (Waiting list) | Mindfulness/relaxation | – | – | – | – | – | + | – | – | – | ||
| Yu238 2002 | Depression | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
Table 6 also reports the combinations of components identified across all studies reporting a depression outcome (at any time point) by population and setting. Components identified were psychoeducation, cognitive, behavioural, mindful, third wave, relaxation, physiological, exercise and CBM. There were 123 active intervention arms from the 105 studies reporting a self-reported depression outcome. Of these active intervention arms, 72 had a psychoeducation component, 96 had a cognitive component, 100 had a behavioural component, 11 had mindful components, seven had third-wave components, 61 had a relaxation component, two had an exercise component and one had a CBM component. The most frequently identified combinations were psychoeducation + cognitive + behavioural (26 study arms), psychoeducation + cognitive + behavioural + relaxation (28 arms) and cognitive + behavioural + relaxation (17 arms).
Further intervention process and delivery characteristics are reported in Appendix 2. The number of intervention sessions implemented ranged from 2 to 120 [median 10 (IQR 8–12) sessions]. As a proxy for intervention dose, we calculated the intervention intensity as total session time (number of sessions × duration in minutes); this ranged from 135 to 10,800 minutes [median 600 (IQR 450–900) minutes]. Ninety per cent of interventions were delivered to whole classrooms or small groups. In 52 studies, interventions were delivered by a MHP, school counsellor or student psychologist. In 10 studies, interventions were delivered by miscellaneous external professionals. Twenty studies used interventions delivered solely by teachers. Fifteen studies involved a combination of teaching, psychology and other professionals. Three studies implemented interventions via computer. Five studies could not be classified.
Network meta-analysis results
Of the 105 studies in the depression review, 86 studies (50,159 participants) contributed to the NMA for depression. Studies not contributing to the NMA are listed in Appendix 2. The network plot for all studies reporting a depression outcome across all populations and settings is reported in Figure 9. The plot edges (lines) connecting each pair of interventions represent a direct comparison and are proportional to the number of trials making that direct comparison. Intervention ‘nodes’ are proportional to the number of participants randomised to each intervention.
FIGURE 9 Network plot for all eligible studies reporting a depression outcome. OT, occupational therapy; SH, self-help; third wave, third-wave CBT-based therapies. (Figure not reproduced here; see the original article.)
Model details are described in Chapter 2 and Appendix 1. Three models were compared for each analysis. We report the results from an intervention-level main effect, a nested additive component and a full interaction component model. Results are reported by population, setting and follow-up time point. The longer-term follow-ups of 6–12, 13–24 and ≥ 25 months are reported for the main intervention-level model only. When data were available from head-to-head trials, we conducted pairwise meta-analyses. The results are reported alongside NMA results in Table 7. Full NMA and pairwise results are reported in Appendix 4.
| Setting | Intervention | Reference intervention | NMA | Direct meta-analysis | Number of trials | ||
|---|---|---|---|---|---|---|---|
| SMD | 95% CrI | SMD | 95% CrI | ||||
| Universal secondary | CBT | Usual curriculum | –0.04 | –0.16 to 0.07 | –0.05 | –0.17 to 0.06 | 11 |
| CBT + IPT | Usual curriculum | –0.18 | –0.46 to 0.08 | NA | NA | 0 | |
| Behavioural therapy | Usual curriculum | –0.02 | –0.40 to 0.37 | –0.02 | –0.40 to 0.37 | 1 | |
| IPT | Usual curriculum | –0.03 | –0.36 to 0.29 | –0.10 | –0.47 to 0.26 | 1 | |
| Third wave | Usual curriculum | –0.03 | –0.21 to 0.14 | –0.02 | –0.19 to 0.14 | 4 | |
| Universal primary | CBT | Usual curriculum | –0.13 | –0.44 to 0.17 | –0.11 | –0.37 to 0.16 | 6 |
| Behavioural therapy | Usual curriculum | –0.10 | –1.04 to 0.80 | NA | NA | 0 | |
| Targeted secondary | CBT | No intervention | –0.22 | –0.58 to 0.13 | –0.16 | –0.47 to 0.15 | 5 |
| IPT | No intervention | –0.65 | –1.50 to 0.16 | NA | NA | 0 | |
| Third wave | No intervention | –0.68 | –1.83 to 0.47 | NA | NA | 0 | |
| CBM | No intervention | –0.90 | –2.20 to 0.40 | NA | NA | 0 | |
| Exercise | No intervention | –0.28 | –1.13 to 0.58 | –0.28 | –1.12 to 0.57 | 1 | |
| Targeted primary | CBT | Waiting list | –0.48 | –2.49 to 1.50 | –0.48 | –2.48 to 1.47 | 2 |
| Occupational therapy | Waiting list | –0.10 | –2.94 to 2.71 | –0.10 | –2.87 to 2.69 | 1 | |
Universal population, secondary setting
Post intervention
The analysis-specific network diagram is reported in Figure 10. Thirty-four studies (18,094 participants) contributed to the analysis for the main time point of immediately post intervention, of which nine were multiarm trials.119,125–129,131–136,138,139,141,143,144,190,192–203,205–207 Six studies were deemed to be at low risk of bias, and 18 studies were deemed to be at unclear risk of bias, for both random sequence generation and allocation concealment. Five studies were rated as having an unclear risk of bias for randomisation and a low risk of bias for allocation concealment. Three studies were rated as having a low risk of bias for randomisation and an unclear risk of bias for allocation concealment. Two studies were rated as having an unclear risk of bias for randomised sequence generation and a high risk of bias for allocation concealment. Twenty-five studies included an intervention based on CBT, one included an intervention based on IPT and three included an intervention based on a combination of CBT and IPT. Four interventions were based on third wave and one was based on behavioural therapy. All reported results are from a random-effects NMA model unless otherwise stated. Model fit and selection statistics suggested that a consistency model was appropriate. Of the three component models fitted (intervention, additive and full interaction), the additive model was preferred, suggesting evidence for effect modification by components. All model fit statistics are reported in Appendix 3. Results are reported as SMDs and 95% CrIs.
FIGURE 10 Network plot for universal population, secondary setting: post-intervention depression outcome. (Figure not reproduced here; see the original article.)
Intervention-level effects
The between-study posterior median SD (τ) was indicative of moderate heterogeneity (τ 0.15, 95% CrI 0.10 to 0.22). Table 7 reports SMDs (95% CrIs) for each intervention relative to usual curriculum. There was weak evidence of a very small effect of CBT (SMD –0.04, 95% CrI –0.16 to 0.07) in preventing symptoms of depression post intervention. There was weak evidence of a small effect of CBT + IPT (SMD –0.18, 95% CrI –0.46 to 0.08) in preventing symptoms at the post-intervention time point. There was no evidence to suggest that IPT (SMD –0.03, 95% CrI –0.36 to 0.29), third-wave therapies (SMD –0.03, 95% CrI –0.21 to 0.14) or behavioural therapy (SMD –0.02, 95% CrI –0.40 to 0.37) are effective.
Additive model: components nested within intervention
Component-level models were fitted to evaluate whether or not the observed between-study heterogeneity in the intervention model could be explained by differences in intervention components. It was possible to estimate additive component effects in CBT and third-wave interventions.
The between-study posterior median SD was indicative of moderate heterogeneity (τ 0.14, 95% CrI 0.08 to 0.22). All CBT interventions included a cognitive component, and additive effects were estimated for psychoeducation, behavioural, mindful and relaxation components. The regression coefficients are reported in Appendix 3 and suggest that there was no evidence of effect modification by components for CBT interventions. Table 8 reports the SMDs for all specific additive combinations of intervention components. Relative to a usual curriculum control, there was weak evidence that a cognitive plus a behavioural component may be effective at reducing symptoms of depression post intervention in universal secondary settings (SMD –0.11, 95% CrI –0.28 to 0.05). There was a lack of evidence for all other combinations.
| Population/setting/outcome | Main intervention | Components (within main intervention) | Study arms (n) | SMD (95% CrI) | |
|---|---|---|---|---|---|
| Additive model | Full interaction model | ||||
| Universal/secondary/depression | CBT | Cognitive + psychoeducational + behavioural | 11 | 0.01 (–0.12 to 0.13) | –0.03 (–0.15 to 0.09) |
| Cognitive + psychoeducational | 1 | –0.55 (–1.33 to 0.20) | –0.57 (–1.33 to 0.21) | ||
| Cognitive + behavioural + relaxation | 4 | –0.10 (–0.31 to 0.11) | –0.11 (–0.4 to 0.17) | ||
| Cognitive + behavioural | 4 | –0.11 (–0.28 to 0.05) | –0.03 (–0.15 to 0.09) | ||
| Cognitive + psychoeducational + behavioural + relaxation | 6 | 0.02 (–0.18 to 0.22) | 0.02 (–0.20 to 0.24) | ||
| Cognitive + psychoeducational + behavioural + mindfulness + relaxation | 3 | –0.01 (–0.4 to 0.38) | –0.02 (–0.46 to 0.41) | ||
| Cognitive + mindfulness | 0 | –0.70 (–1.6 to 0.18) | – | ||
| Cognitive + relaxation | 0 | –0.66 (–1.47 to 0.13) | – | ||
| Cognitive + psychoeducational + mindfulness | 0 | –0.59 (–1.44 to 0.26) | – | ||
| Cognitive + behavioural + relaxation | 0 | –0.54 (–1.33 to 0.24) | – | ||
| Cognitive + psychoeducational + mindfulness +relaxation | 0 | –0.57 (–1.44 to 0.29) | – | ||
| Cognitive + psychoeducational + behavioural + mindfulness | 0 | –0.03 (–0.4 to 0.35) | – | ||
| Cognitive + behavioural + mindfulness | 0 | –0.14 (–0.59 to 0.30) | – | ||
| Cognitive + behavioural + mindfulness + relaxation | 0 | –0.13 (–0.58 to 0.32) | – | ||
| Cognitive + mindfulness + relaxation | 0 | –0.69 (–1.6 to 0.21) | – | ||
| Third wave | Third wave + psychoeducational | 1 | –0.05 (–0.38 to 0.27) | –0.05 (–0.40 to 0.30) | |
| Third wave + mindfulness + relaxation | 3 | 0.10 (–0.12 to 0.33) | 0.11 (–0.13 to 0.35) | ||
| Third wave + psychoeducational + mindfulness + relaxation | 1 | –0.35 (–0.70 to 0.00) | –0.35 (–0.72 to 0.02) | ||
All third-wave interventions contained a third-wave component, and additive effects were estimated for psychoeducation and a combined mindfulness + relaxation component. Owing to the data structure, it was not possible to estimate the effects for mindfulness and relaxation components separately. The impact of including a psychoeducation component in third-wave interventions was to reduce the SMD by –0.45 (β –0.45, 95% CrI –0.87 to –0.04). Although this regression coefficient indicates the presence of effect modification, Table 8 shows that there was still only weak evidence that a third-wave intervention (when made up of third wave + mindfulness + relaxation components) is effective at reducing symptoms of depression relative to a usual curriculum (SMD –0.35, 95% CrI –0.70 to 0.00). We note that this is based on evidence from a single study.
Full interaction model: components nested within intervention
Table 8 also reports the number of studies comparing each unique combination of components for CBT and third-wave interventions for the full interaction component model. Model fit and regression coefficients are reported in Appendix 3. The between-study posterior median SD for the full interaction model was suggestive of moderate heterogeneity (τ 0.15, 95% CrI 0.10 to 0.23). There was no evidence of a differential effect of CBT or third wave by intervention components in universal secondary settings.
Universal, secondary, further time points: intervention-level effects
Six to 12 months post intervention
Twenty-eight studies (19,817 participants) contributed to the analysis for 6–12 months post intervention, eight of which were multiarm trials.118,125,126,128,129,131,133–136,138,139,141–143,194–203,205–207 Twenty-one studies included an intervention based on CBT, four studies included a CBT + IPT intervention and one study evaluated an IPT-based intervention. Three studies included a third-wave-based intervention. The between-study posterior median SD was indicative of low heterogeneity (τ 0.08, 95% CrI 0.02 to 0.15). There was weak evidence, of small effects, to suggest that CBT (SMD –0.02, 95% CrI –0.10 to 0.06), CBT + IPT (SMD –0.10, 95% CrI –0.26 to 0.05) and third-wave interventions (SMD –0.13, 95% CrI –0.27 to 0.01) could prevent symptoms of depression, compared with a usual curriculum comparator. The third-wave studies were judged to be at low risk of bias. The CBT and CBT + IPT studies were judged to be at mostly unclear risk of selection bias (see Appendix 2). There was no evidence to support IPT (SMD 0.11, 95% CrI –0.13 to 0.35) reducing symptoms at 6–12 months, relative to usual curriculum.
Thirteen to 24 months post intervention
Eight studies (7584 participants) contributed to the analysis for 13–24 months post intervention, seven of which included an intervention based on CBT and one that included an intervention based on CBT + IPT.136,138,139,194,197,204,206,207 There was no evidence to suggest that CBT-based (SMD –0.04, 95% CrI –0.20 to 0.14) or CBT + IPT (SMD –0.10, 95% CrI –0.57 to 0.39) interventions prevented symptoms of depression at 13–24 months, relative to usual curriculum. The between-study posterior median SD was indicative of low heterogeneity (τ 0.07, 95% CrI 0.00 to 0.35).
Twenty-five or more months post intervention
We combined studies reporting time points closest to 36 months post intervention. Three studies (1303 participants) reported time points between 30 and 36 months post intervention.138,194,206 All evaluated a CBT intervention. There was no evidence of an effect for preventing symptoms (SMD –0.14, 95% CrI –2.89 to 2.63), compared with usual curriculum.
Universal population, primary setting
Post intervention
The analysis-specific network diagram is reported in Figure 11. Twelve studies (4116 participants) contributed to the analysis for the main time point of immediately post intervention.145,147,150–152,155–157,208,209,211,212 Eleven included an intervention based on CBT and one study evaluated a behavioural intervention. Model fit and selection statistics were suggestive of slight lack of fit, but a consistency model was preferred. Model fit was similar across all three component models fitted (intervention, additive and full interaction), but suggests that the intervention-level model was appropriate (see Appendix 3). Therefore, we report effect estimates from the random-effects intervention-level NMA only. Regression coefficients from the additive and full interaction models are reported in Appendix 3.
FIGURE 11 Network plot for universal population, primary setting: post-intervention depression outcome. (Figure not reproduced here; see the original article.)
Intervention-level effects
The between-study posterior median SD was indicative of moderate to substantial heterogeneity (τ 0.32, 95% CrI 0.18 to 0.59). Table 7 reports SMDs (95% CrIs) for each intervention, relative to usual curriculum. There was a lack of evidence that CBT (SMD –0.13, 95% CrI –0.44 to 0.17) or behavioural therapy (SMD –0.10, 95% CrI –1.04 to 0.80) reduced self-reported symptoms of depression post intervention.
Additive model: components nested within intervention
The between-study posterior median SD was indicative of high heterogeneity (τ 0.37, 95% CrI 0.20 to 0.70). All CBT interventions included a cognitive and a behavioural component, and additive effects could be estimated for psychoeducation and relaxation components only. However, there was no evidence for effect modification; regression coefficients are reported in Appendix 3, Table 40.
Full interaction model: components nested within intervention
The between-study posterior median SD was suggestive of high heterogeneity (τ 0.39, 95% CrI 0.21 to 0.78). There was no evidence of effect modification by intervention components for CBT in universal primary settings; regression coefficients are reported in Appendix 3, Table 40.
Universal, primary, further time points: intervention-level effects
Six to 12 months post intervention
Nine studies (4134 participants) contributed to the analysis for 6–12 months post intervention, all of which evaluated a CBT-based intervention.145,150–152,155,157,159,208,211 The between-study posterior median SDs were indicative of moderate to substantial heterogeneity (τ 0.21, 95% CrI 0.06 to 0.56). There was weak evidence, of a small effect, that CBT prevents symptoms of depression at 6–12 months, relative to usual curriculum (SMD –0.15, 95% CrI –0.43 to 0.09).
Thirteen to 24 months post intervention
Three studies (1602 participants) contributed to the analysis for 13–24 months post intervention, all of which included an intervention based on CBT.152,157,159 There was no evidence to suggest that CBT-based interventions prevented symptoms of depression at 13–24 months, relative to usual curriculum (SMD –0.03, 95% CrI –0.62 to 0.55).
Twenty-five or more months post intervention
One study (910 participants) reported a follow-up time point of 30 months post intervention.152 There was evidence that CBT prevented symptoms of depression at 30 months’ follow-up (SMD –0.27, 95% CrI –0.42 to –0.13).
Targeted population, secondary setting
Post intervention
The analysis-specific network diagram for targeted secondary settings is reported in Figure 12. Twenty-four studies (3669 participants) contributed to the analysis for the main time point of immediately post intervention.114,141,160–163,165,167,170,173,214,215,217–219,221–224,226–230 Four studies were deemed to be at low risk of bias and seven studies were deemed to be at unclear risk of bias for both random sequence generation and allocation concealment. Eleven studies were judged to be at low risk of bias for random sequence generation but at unclear risk of bias for allocation concealment, and two studies were judged to be at unclear risk of bias for random sequence generation but at low risk of bias for allocation concealment. Eighteen studies included an intervention based on CBT, three studies included IPT-based interventions, one study evaluated a third-wave intervention, one included a CBM intervention and one evaluated an exercise intervention. Model fit and selection statistics were suggestive of slight lack of fit, but a consistency model was considered reasonable. Model fit was similar across all three component models (intervention, additive and full interaction). Reported results are from a random-effects, consistency intervention-level NMA. Full model fit details are provided in Appendix 3.
FIGURE 12 Network plot for targeted population, secondary setting: post-intervention depression outcome. (Figure not reproduced here; see the original article.)
Intervention-level effects
There was evidence of moderate to substantial between-study heterogeneity (τ 0.38, 95% CrI 0.25 to 0.58). Table 7 reports SMDs (95% CrIs) for each intervention relative to no intervention. There was no evidence of an effect for any intervention: CBT (SMD –0.22, 95% CrI –0.58 to 0.13); CBM (SMD –0.90, 95% CrI –2.20 to 0.40); IPT (SMD –0.65, 95% CrI –1.50 to 0.16); exercise (SMD –0.28, 95% CrI –1.13. to 0.58); and third wave (SMD –0.68, 95% CrI –1.83 to 0.47).
Component models: additive and full interaction
Regression coefficients are reported for both the additive and full interaction models in Appendix 3, Table 42. There was no evidence of effect modification according to components for CBT interventions in a targeted secondary setting.
Targeted, secondary, further time points: intervention-level effects only
Six to 12 months post intervention
Seventeen studies (2728 participants) contributed to the analysis for 6–12 months post intervention, of which 14 included a CBT-based intervention and three included an IPT intervention.141,160,163,165,173,214,218,219,221–224,226–230 There was evidence of high levels of between-study heterogeneity (τ 0.44, 95% CrI 0.27 to 0.71). There was no evidence that either CBT (SMD –0.04, 95% CrI –0.51 to 0.41) or IPT (SMD –0.49, 95% CrI –1.49 to 0.48) prevented symptoms of depression at 6–12 months, relative to no intervention.
Thirteen to 24 months post intervention
Five studies (1089 participants) provided data for the NMA of 13–24 months’ follow-up.166,218,223,224,229 Four evaluated a CBT intervention and one evaluated an IPT-based intervention. Between-study heterogeneity was high (τ 0.58, 95% CrI 0.12 to 3.08). There was no evidence that CBT (SMD –0.18, 95% CrI –2.56 to 2.16) or IPT (SMD 0.09, 95% CrI 3.81 to 3.93) reduced symptoms of depression at 13–24 months post intervention.
Twenty-five or more months post intervention
One study (260 participants), judged to be at unclear risk of bias, provided no evidence to suggest that CBT prevented symptoms at 48 months’ follow-up (SMD –0.27, 95% CrI –1.05 to 0.50).166
Targeted population, primary setting
Post intervention
The analysis-specific network diagram for targeted primary settings is reported in Figure 13. Five studies (497 participants) contributed to the analysis for the post-intervention time point, of which four included an intervention based on CBT, and one examined an occupational therapy-based intervention.175,179–181,232 One study was deemed to be at low risk of bias for both random sequence generation and allocation concealment, and three studies were deemed to be at unclear risk of bias. One study was deemed to be at low risk of bias for random sequence generation but at unclear risk of bias for allocation concealment. Model fit statistics are reported in Appendix 3. There were limited data available for the component-level models; however, model fit was similar across the three models. The between-study posterior median SD was lowest for the intervention-level model; it is on this basis that the intervention-level model is preferred here (see Appendix 3). All reported results are from a consistency random-effects NMA model unless otherwise stated.
FIGURE 13 Network plot for targeted population, primary setting: post-intervention depression outcome. OT, occupational therapy. (Figure not reproduced here; see the original article.)
Intervention-level effects
There was evidence of substantial between-study heterogeneity (τ 0.60, 95% CrI 0.08 to 3.80). Table 7 reports SMDs (95% CrIs) for each intervention relative to a waiting list. There was no evidence of an effect for CBT (SMD –0.48, 95% CrI –2.49 to 1.50) or occupational therapy (SMD –0.10, 95% CrI –2.94 to 2.71) at the immediate post-intervention time point.
Component models: additive and full interaction
For the additive component model, the between-study posterior median SD tended to the prior (τ 2.48, 95% CrI 0.12 to 4.87), as did the regression coefficient for occupational therapy (β –8.97, 95% CrI –144.7 to 144.5). As a result, we conclude that data were insufficient to estimate additive or full interaction effects for targeted primary settings.
Targeted, primary, further time points: intervention-level effects only
Two studies (230 participants) reported follow-up at 6–12 months, both of which included a CBT-based intervention.175,232 A fixed-effects NMA was conducted. There was weak evidence that CBT (SMD –0.34, 95% CrI –0.72 to 0.05) prevented symptoms of depression at 6–12 months, relative to a waiting list. There was weak evidence from one study (83 participants), judged to be at unclear risk of bias, that CBT prevented symptoms of depression at 24 months’ follow-up, compared with a waiting list (SMD –0.50, 95% CrI –0.96 to 0.05).232
Targeted population, tertiary/university setting
The analysis-specific network diagram is reported in Figure 14. Five studies (789 participants) contributed to the analysis for the main time point of post intervention, four of which included an intervention based on CBT and one of which included an intervention based on behavioural therapy.183,184,186,187,235 Model fit and selection statistics suggested that a random-effects consistency model was reasonable (see Appendix 3); however, the between-study posterior median SD was indicative of substantial heterogeneity (τ 0.51, 95% CrI 0.12 to 2.50). This was considerably reduced in the unrelated intervention effects model (τ 0.26, 95% CrI 0.02 to 2.48), and may indicate the presence of inconsistency. Therefore, results for the tertiary setting are not reported. This possible inconsistency should also be interpreted in the light of the inclusion criteria adopted in this review, that interventions needed to be delivered in the educational institution itself, and the unanticipated limitations it caused for the tertiary/university setting analyses. We consider the limitations in Chapter 10.
FIGURE 14 Network plot for targeted population, tertiary/university setting: post-intervention depression outcome. (Figure not reproduced here; see the original article.)
Exploring heterogeneity and small-study effects
Subgroup analyses, metaregression and sensitivity analyses were conducted for the intervention-level NMA, for the main outcome and primary end point of post intervention only. Comparison-adjusted funnel plots did not provide evidence of small-study effects (see Appendix 6). However, the small number of studies available for the primary settings makes interpretation difficult.
Metaregression was conducted for intervention mode of delivery (face to face or via computer) and for intervention facilitator (teacher or a MHP). There was no evidence of effect modification by facilitator or mode of delivery for any population or setting combination (see Appendix 6).
Subgroup analyses were conducted to assess whether or not intervention effects differed by intended focus of the intervention, for example whether or not interventions addressing depression had a larger effect on anxiety outcomes than interventions intended to focus on anxiety but which also recorded depression outcomes. For each population and setting combination, intervention estimates were compared across three subgroups: (1) interventions that aimed to prevent anxiety (2) interventions that aimed to prevent depression only and (3) interventions that aimed to prevent both anxiety and depression. The results are reported in Appendix 6 but should be considered descriptive only. For the universal secondary network, there was some evidence that intervention focus was important. Interventions focused on preventing depression appear to have a larger effect on self-reported symptoms of depression than those focusing on anxiety or combined depression and anxiety. However, CrIs overlap, and we did not conduct a statistical test to examine subgroup differences.
Sensitivity analyses: risk of bias
Sensitivity analyses were conducted for the intervention-level NMA, for the main outcome and primary end point of post intervention only. We explored the robustness of the findings to excluding studies judged to be at high/unclear risk of bias for the randomised sequence generation and allocation concealment domains.
Having removed studies judged to be at high/unclear risk of bias for randomisation and allocation concealment, only six studies of six interventions remained in the universal secondary depression network.125,126,141,196,197,201 However, only five studies formed a connected network.125,126,141,196,201 Restricting to studies judged to have a low risk of bias, there was no evidence that CBT (SMD 0.02, 95% CrI –0.77 to 0.80) or third-wave (SMD –0.35, 95% CrI –1.15 to 0.45) interventions are effective to prevent symptoms of depression in universal secondary settings (Table 9). For targeted secondary interventions, only four studies of four interventions could be included in the analysis of studies judged to have a low risk of bias, and there was no evidence that CBT was effective.141,167,219,226 One study was judged to be at low risk of bias in the universal primary network.145 A sensitivity analysis was not possible for the targeted primary network.
| Population/setting | Reference intervention | Intervention | Number of studies | SMD (95% CrI) | |
|---|---|---|---|---|---|
| Low risk of bias studies | All studies | ||||
| Universal secondary | Usual curriculum | CBT | 5 | 0.02 (–0.77 to 0.80) | –0.04 (–0.16 to 0.07) |
| Usual curriculum | Third wave | –0.35 (–1.15 to 0.45) | –0.03 (–0.21 to 0.14) | ||
| Universal primary | Usual curriculum | CBT | 1 | –0.10 (–0.29 to 0.09)a | –0.13 (–0.44 to 0.17) |
| Targeted secondary | No intervention | CBT | 4 | 0.07 (–1.33 to 1.49) | –0.22 (–0.58 to 0.13) |
Sensitivity analyses: intracluster correlation coefficient and change from baseline scores
When cluster-randomised trials did not explicitly account for clustering in their analyses, we followed the advice in the Cochrane handbook (section 16.3.4)81 for calculating an approximate sample size, using an ICC of 0.03. We explored the robustness of this decision in a best-case/worst-case sensitivity analysis using ICCs of 0.01 and 0.06, respectively. Results were robust to alternative ICC values.
When necessary, we derived mean change from baseline from reported baseline and follow-up means and SDs. To do so, we assumed a correlation coefficient of 0.7, which was based on previous analyses.82 We conducted sensitivity analyses using correlation values of 0.6 and 0.8. Results were robust to alternative correlation values (see Appendix 6).
Summary of main results
A total of 105 studies met the inclusion criteria for the depression prevention review, of which 88 were judged to be at high or unclear risk of bias for random sequence generation and/or allocation concealment. Eighty-six studies contributed data to the NMA across all settings and time points. Moderate levels of heterogeneity were observed in all analyses, and high levels of heterogeneity were observed in some analyses. There was no suggestion of small-study effects in the depression networks.
At the primary time point of post intervention, there was weak evidence from 34 studies to suggest that CBT (SMD –0.04, 95% CrI –0.16 to 0.07) and CBT + IPT (SMD –0.18, 95% CrI –0.46 to 0.08) may be effective in universal secondary settings. In all other populations and settings, there was no evidence to suggest that any type of intervention was effective for preventing depression at the post-intervention time point. The interpretation of these results and the implications for conclusions are presented in Chapter 9.
At 6–12 months’ follow-up, there was weak evidence to suggest that CBT (SMD –0.02, 95% CrI –0.10 to 0.06), CBT + IPT (SMD –0.10, 95% CrI –0.26 to 0.05) and third-wave interventions (SMD –0.13, 95% CrI –0.27 to 0.01) may reduce depression, compared with usual curriculum, in universal secondary settings. There was also weak evidence that CBT reduced self-reported depression at 6–12 months, relative to usual curriculum, in universal primary settings (SMD –0.15, 95% CrI –0.43 to 0.09), and relative to a waiting list in targeted primary settings (SMD –0.34, 95% CrI –0.72 to 0.05). In targeted primary settings, there was weak evidence, from a single study judged to be at unclear risk of bias, for the beneficial effect of CBT-based interventions (relative to a waiting list) at 13–24 months’ follow-up (SMD –0.50, 95% CrI –0.96 to 0.05).
In all other populations and settings, at all remaining time points, there was an absence of evidence that any type of intervention was effective.
Owing to possible statistical inconsistency, we do not report the results for tertiary education settings. As noted in Chapter 4, we consider this, and the limitations imposed by the inclusion criteria on the validity of the tertiary/university network, in Chapter 10.