Background Rates of anxiety and depression are increasing among children and young people. Recent policies have focused on primary prevention of mental disorders in children and young people, with schools at the forefront of implementation. There is limited information for the comparative effectiveness of the multiple interventions available. MethodsWe did a systematic review and network meta-analysis, searching MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled trials for published and unpublished, passive and active-controlled randomised and quasi-randomised trials. We included educational setting-based, universal, or targeted interventions in which the primary aim was the prevention of anxiety and depression in children and young people aged 4-18 years. Primary outcomes were post-intervention self-report anxiety and depression, wellbeing, suicidal ideation, or selfharm. We assessed risk of bias following the Cochrane Handbook for Systematic Reviews of Interventions. We estimated standardised mean differences (SMD) using random effects network meta-analysis in a Bayesian framework. The study is registered with PROPSERO, number CRD42016048184.Findings 1512 full-text articles were independently screened for inclusion by two reviewers, from which 137 studies of 56 620 participants were included. 20 studies were assessed as being at low risk of bias for both random sequence generation and allocation concealment. There was weak evidence to suggest that cognitive behavioural interventions might reduce anxiety in primary and secondary settings. In universal secondary settings, mindfulness and relaxation-based interventions showed a reduction in anxiety symptoms relative to usual curriculum (SMD -0•65, 95% credible interval -1•14 to -0•19). There was a lack of evidence to support any one type of intervention being effective to prevent depression in universal or targeted primary or secondary settings. Comparison-adjusted funnel plots suggest the presence of small-study effects for the universal secondary anxiety analysis. Network meta-analysis was not feasible for wellbeing or suicidal ideation or self-harm outcomes, and results are reported narratively.Interpretation Considering unclear risk of bias and probable small study effects for anxiety, we conclude there is little evidence that educational setting-based interventions focused solely on the prevention of depression or anxiety are effective. Future research could consider multilevel, systems-based interventions as an alternative to the downstream interventions considered here.

Public health and health service interventions are typically complex: they are multifaceted, with impacts at multiple levels and on multiple stakeholders. Systematic reviews evaluating the effects of complex health interventions can be challenging to conduct. This paper is part of a special series of papers considering these challenges particularly in the context of WHO guideline development. We outline established and innovative methods for synthesising quantitative evidence within a systematic review of a complex intervention, including considerations of the complexity of the system into which the intervention is introduced. We describe methods in three broad areas: non-quantitative approaches, including tabulation, narrative and graphical approaches; standard meta-analysis methods, including meta-regression to investigate study-level moderators of effect; and advanced synthesis methods, in which models allow exploration of intervention components, investigation of both moderators and mediators, examination of mechanisms, and exploration of complexities of the system. We offer guidance on the choice of approach that might be taken by people collating evidence in support of guideline development, and emphasise that the appropriate methods will depend on the purpose of the synthesis, the similarity of the studies included in the review, the level of detail available from the studies, the nature of the results reported in the studies, the expertise of the synthesis team and the resources available.

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