Efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction for Depression Symptoms and Sleep-Wake Disruption in Older and Younger Adults: Secondary Age-Stratified Analysis of a Randomized Controlled Trial

•What is the primary question addressed by this study?Is there preliminary evidence for efficacy and mechanism-of-action, of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms?•What is the main finding of this study?TranS-C improved depression response rates 6-months postintervention. During the acute treatment phase, improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults) correlated with the degree of depression symptom reductions 6-months later.•What is the meaning of the finding?Future studies are warranted to confirm that TranS-C, a targeted sleep-wake treatment, improves the durability of depression symptom response via the identified pathways. Perform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms. Secondary analysis of a randomized controlled trial with convenience age subsamples (younger (20–49 year; n = 52) versus and older (50–71 years; n = 35)). Community mental health clinics. Eighty-seven adults with serious mental illness. TranS-C versus treatment as usual (TAU). Outcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude). Depression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ2 = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = −0.40, 95% confidence interval (CI): −0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: −0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = −0.52, n = 15, p = 0.049). Confirmatory trials are needed, given the low age-specific sample sizes here, to determine if T