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IntroductionDespite carrying a disproportionately high burden of depression, patients in low-income countries lack access to effective care. The collaborative care model (CoCM) has robust evidence for clinical effectiveness in improving mental health outcomes. However, evidence from real-world implementation of CoCM is necessary to inform its expansion in low-resource settings.MethodsWe conducted a 2-year mixed-methods study to assess the implementation and clinical impact of CoCM using the WHO Mental Health Gap Action Programme protocols in a primary care clinic in rural Nepal. We used the Capability Opportunity Motivation-Behaviour (COM-B) implementation research framework to adapt and study the intervention. To assess implementation factors, we qualitatively studied the impact on providers’ behaviour to screen, diagnose and treat mental illness. To assess clinical impact, we followed a cohort of 201 patients with moderate to severe depression and determined the proportion of patients who had a substantial clinical response (defined as ≥50% decrease from baseline scores of Patient Health Questionnaire (PHQ) to measure depression) by the end of the study period.ResultsProviders experienced improved capability (enhanced self-efficacy and knowledge), greater opportunity (via access to counsellors, psychiatrist, medications and diagnostic tests) and increased motivation (developing positive attitudes towards people with mental illness and seeing patients improve) to provide mental healthcare. We observed substantial clinical response in 99 (49%; 95% CI: 42% to 56%) of the 201 cohort patients, with a median seven point (Q1:−9, Q3:−2) decrease in PHQ-9 scores (p<0.0001).ConclusionUsing the COM-B framework, we successfully adapted and implemented CoCM in rural Nepal, and found that it enhanced providers’ positive perceptions of and engagement in delivering mental healthcare. We observed clinical improvement of depression comparable to controlled trials in high-resource settings. We recommend using implementation research to adapt and evaluate CoCM in other resource-constrained settings to help expand access to high-quality mental healthcare.