Understanding how interventions for youth depression and anxiety work: Recommendations for mechanistic research is a comprehensive report commissioned by Wellcome that examines why many interventions for anxiety and depression in children and adolescents show only modest, inconsistent, or short-lived benefits. Drawing on an umbrella review of more than 200 reviews and meta-analyses, alongside consultation with young people with lived experience and international experts, the report highlights a critical gap: while many interventions reduce symptoms, there is still limited understanding of how, why, and for whom they work.
The report focuses on interventions for children and young people under 18 across psychological, pharmacological, digital, lifestyle, social, and creative domains, and is intended to inform future Wellcome funding by strengthening mechanistic, prevention-focused, and youth-centred research.
Key Challenges Identified
- Weak mechanistic evidence
Many interventions are theory-informed but rarely test mechanisms directly. Trials often evaluate whole interventions rather than isolating active ingredients, with limited use of mediation, dose–response, or temporal sequencing analyses. - Limited prevention research
Most studies focus on treating existing or subclinical symptoms rather than targeting underlying risk factors before onset. Primary prevention research remains scarce, despite its potential to reduce lifetime burden. - Narrow geographic and cultural focus
Evidence is heavily concentrated in high-income countries, with limited adaptation or testing in low- and middle-income countries (LMICs), where unmet need is greatest. - Insufficient lived experience integration
Young people’s perspectives are rarely embedded in study design or outcome selection, leading to a mismatch between what research measures and what young people find meaningful (e.g. trust, agency, relationships, belonging).
Priority Areas for Future Research
Design studies that explicitly test mechanisms
- Use clear theories of change and hypothesis-driven designs
- Employ innovative methods such as mediation analyses, N-of-1 studies, adaptive and factorial trials
- Move beyond pre–post symptom change to examine pathways of change over time
Strengthen prevention and risk-factor research
- Invest in mechanistic studies that target causal risk and protective factors
- Distinguish prevention from treatment effects through better screening and longer follow-up
- Identify optimal developmental windows for early intervention
Expand research in LMICs and diverse contexts
- Test whether mechanisms are universal or context-specific
- Support culturally adapted, locally led research
- Address structural and access barriers alongside intervention effects
Advance under-researched but promising interventions
- Lifestyle interventions (physical activity, sleep, nutrition): clarify biological and psychosocial pathways and optimal “dose”
- Social and interpersonal interventions: refine models linked to relationships, trust, and belonging
- Creative and spiritual interventions: rigorously test mechanisms such as identity, meaning-making, and emotional regulation
Embed lived experience throughout the research cycle
- Co-design studies with young people
- Define outcomes that reflect youth priorities, not only symptom reduction
- Improve real-world relevance, acceptability, and ethical practice
Why This Matters
The report calls for a shift from asking “does it work?” to “how does it work, for whom, and in which contexts?”. By strengthening mechanistic understanding and centring youth experience, the field can move toward more precise, equitable, and scalable mental health interventions—supporting earlier, more effective responses to anxiety and depression worldwide.
Read the full report, Understanding how interventions for youth depression and anxiety work: Recommendations for mechanistic research (PDF).
