What works and for whom in treating depression in older adults in deprived communities in Brazil: Findings from a causal mediation analyses of the PROACTIVE trial that overlapped with the COVID-19 pandemic

Background The PROACTIVE trial was a task-shared, collaborative care, psychosocial intervention that was highly effective at improving recovery from depression in older adults in Brazil that overlapped with the COVID-19 pandemic. Here we investigate mediators of the intervention’s effectiveness. Methods Causal mediation analysis using interventional indirect effects, decomposed the total effect of PROACTIVE on recovery from depression (PHQ-9<10), into multiple indirect effects including: dose of intervention (number of sessions and number of activities completed); social support measured through Luben Social Network Scale; perceived loneliness through the three-item UCLA questionnaire; conditions associated with frailty; and extra sessions offered to participants who did not respond to the intervention. Findings Of the intervention’s total effect (difference in probability of recovery from depression between the intervention and control arms 0·211 [bias-corrected 95% CI: 0·139, 0·274]): 14% was mediated through improved conditions associated with frailty 0·030 [0·003, 0·065]); 6% through reduced loneliness (0·013 [0·001, 0·028]); and 20% through attending extra sessions for participants who did not respond to the intervention (0·042 [0·007, 0·105]). Interpretation Our findings emphasise the importance of a home-based intervention to improve depression outcomes where participants are encouraged to self-select activities to mitigate against loneliness and are referred to primary care to manage health issues relating to frailty. Importantly, our findings suggest that offering extra sessions to participants who did not respond to the intervention shows promise in ensuring a sustained recovery from depression. Funding São Paulo Research Foundation and Joint Global Health Trials UK. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN57805470 ### Funding Statement Sao Paulo Research Foundation and Joint Global Health Trials UK ### 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: This study was approved by the Ethics Committee of Universidade de Sao Paulo Medical School (CEP FMUSP number 2.836.569) and authorised by the Guarulhos Health Secretary 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data available upon request