Abstract Background Depression is a common mental health disorder which frequently co-occurs with increased body mass index or increased waist circumference (hereafter ‘overweight’), causing heightened cardiovascular risk. Unhealthy lifestyle behaviours underlie both conditions. The Multimodal Lifestyle Intervention (MLI) LEEF integrates physical activity, nutrition, and behavioural strategies, tailored to motivational challenges common in depression, offering a dual focus on mental and physical health. However, unpublished process data revealed very limited referral to MLI‑LEEF from both primary and secondary care, and consequently low initiation rates, signalling clear implementation challenges. This study addresses this gap by translating prioritised implementation determinants into conceptually and empirically grounded implementation strategies and examining what works, how, and under which conditions. Methods This quasi‑experimental, explanatory sequential mixed‑methods study will implement MLI‑LEEF across ten general practices and three secondary mental health care outpatient clinics in the Northern Netherlands. Implementation strategies will be developed and tailored using Causal Pathway Diagramming and applied over a six‑month period. Quantitative data will be collected before, during, and after implementation to assess proximal implementation outcomes (the immediate, observable effects of an implementation strategy), distal implementation outcomes (adoption and sustainability), service‑level penetration, and patient outcomes. Following the implementation period, semi‑structured interviews will be conducted with referrers from each participating organisation. Site‑specific topic guides, informed by each organisation’s implementation plan, causal pathway diagrams, and quantitative implementation outcomes, will probe how strategies generate change (mechanisms), how they influence targeted determinants, and which contextual conditions (preconditions, moderators) shape implementation strategy functioning. Discussion This study will respond to fieldwide calls in implementation science for rigorous, transparent, and context-sensitive approaches to developing and evaluating implementation strategies. By examining how strategies shape referral and initiation in routine general practice and specialist mental health services, and by clarifying the mechanisms and contextual conditions under which they are effective, the study will generate actionable insight into why implementation succeeds or falters in real-world care. These insights will provide essential groundwork for strengthening the reach and adoption of MLI-LEEF and will offer transferable guidance for embedding multimodal lifestyle interventions into everyday care, while advancing generalizable knowledge of how implementation strategies produce change. Trial registration 10.17605/OSF.IO/XJHCB.
Geelen et al. (2026) studied this question.