Abstract
<p>Background: Randomised trials evaluating psychological interventions for perinatal depression (PND) in low- and middle-income countries (LMICs) frequently provide conflicting findings. To optimise global maternal mental health interventions, we applied robust causal inference and causal machine learning approaches to individual participant data (IPD) to identify underlying causal mechanisms and responsive subgroups.Methods: We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and the Cochrane Library from inception to November 19, 2025, for trials assessing the effectiveness of psychological interventions to treat PND. Using IPD, we assessed treatment effect heterogeneity using causal forests, and evaluated causal mechanisms using interventional effects for individual trials and across relevant pooled datasets.Findings: Seven of 11 eligible studies provided IPD, yielding a pooled sample of 3,154 participants (1,700 intervention, 1,454 control). Heterogeneity analyses of all trials demonstrated top responders presented with higher baseline depression and lower education. A four-study subset incorporating social determinants revealed those with lower perceived social support and education responded best. This four-study subset comprised two two-trial subsets: one delivered by community health workers (CHWs) and one by peers. In the CHW-delivered subset, top responders were similar to the four-study subset; however, within the peer-delivered subset, this effect was negligible. Causal mediation analyses of the four trials revealed social support mediated a 15% symptom reduction. The two-trial CHW subset indicated social support and reduced food insecurity mediated 15% and 3% improvements, respectively. Furthermore, a specific two-trial subset indicated behavioural activation and social support mediated improvements of 32% and 17%.Interpretation: Despite interventions effectively targeting perceived social support, trials capturing food insecurity demonstrated minimal impact. The failure of peer-delivered interventions to reach vulnerable women, unlike CHW-delivered trials, suggests highly disadvantaged populations benefit least from a lower-cadre workforce. Optimising global maternal mental health requires assertively targeting socioeconomic determinants such as food insecurity and deploying CHWs to support the most vulnerable populations.</p>