Understanding how a digital mental health intervention can be optimised to ensure effectiveness in the longer-term: findings from a causal mediation analyses of the CONEMO trials

Background Two CONEMO trials in Lima, Peru and São Paulo, Brazil evaluated a digital mental health intervention (DMHI) based on behavioural activation (BA) that demonstrated improvements in symptoms of depression between trial arms at three-months, but not at six-months. To understand how we can optimize CONEMO in the longer-term, we therefore aim to investigate mediators through which the DMHI improved symptoms of depression at six-months, separately for the two trials and then using a pooled dataset. Methods We used data that included adults with depression (Patient Health Questionnaire – 9 (PHQ-9) score ≥10) and comorbid hypertension and/or diabetes. Interventional effects were used to decompose the total effect of DMHI on symptoms of depression at six months into indirect effects via: understanding the content of the sessions without difficulty; number of activities completed that were self-selected to improve levels of BA; and levels of activation measured using the Behavioural Activation for Depression Short Form (BADS-SF). Findings Using the pooled dataset, understanding the content of the sessions without difficulty mediated a 10% [0.10: 95% CI: 0.03 to 0.15] improvement in PHQ-9 scores at six months; completing self-selected activities mediated a 12% improvement [0.12: 0.01 to 0.23]; and, lastly, BA mediated a 2% [0.02: 0.01, 0.05] improvement. Conclusions Our findings suggest that targeting participants to complete activities they find enjoyable will help to improve levels of activation and maintain the effect of the CONEMO intervention in the longer-term. Improving the content of the sessions to facilitate understanding can also help to maintain improvements. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial protocol received ethical approval in Brazil by the Institutional Review Board at the University of Sao Paulo (457.605) and the National Commission of Ethics in Research (355.039). In Lima, the protocol was approved by the Institutional Review Board at the Universidad Peruana Cayetano Heredia (34516-16). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data will be made available publicly once all analyses from trial data is complete