Effectiveness of app-based cognitive behavioral therapy for insomnia on preventing major depressive disorder in youth with insomnia and subclinical depression: A randomized clinical trial

Background: Insomnia is an independent risk factor for depression. This randomized controlled trial tested whether app-based cognitive behavioral therapy for insomnia (CBT-I) prevents future major depressive disorder (MDD) in youth. Methods and findings: In a randomized, assessor-blind, parallel-group trial, Chinese youth aged 15–25 years with insomnia disorder and subclinical depressive symptoms were assigned 1:1 to a 6-week app-based CBT-I or an attention-matched 6-week app-based health education (HE) control. Primary outcome was time to onset of MDD over 12 months, assessed via telephone Mini-International Neuropsychiatric Interview (MINI). Secondary outcomes were depressive and insomnia symptoms and insomnia disorder remission. From Sept 9, 2019 to Nov 25, 2022, 708 participants (57% female; mean age 22.1 years) were randomized (CBT-I n=354; HE n=354). Over 12 months, 10% (37/354) in CBT-I and 18% (62/354) in HE developed MDD (HR 0.58, 95% CI 0.38–0.87; p=0.008); number needed to treat at 1 year = 10.9 (6.8–26.6). Insomnia remission favored CBT-I at post-intervention (52% vs 28%; RR 1.83, 95% CI 1.49–2.24; p<0.001) and at 6 and 12 months. CBT-I produced greater reductions in depressive symptoms (adjusted difference –1.0 PHQ-9 points [–1.6 to –0.5]; d=0.53; p<0.001) and insomnia severity (–2.0 ISI points [–2.7 to –1.3]; d=0.78; p<0.001) at post-intervention, with effects sustained to 6 months. Mediation analyses indicated insomnia improvement mediated effects on depression. No intervention-related adverse events were reported. Conclusions: App-based CBT-I prevents onset of major depression and improves insomnia outcomes in youth with insomnia and subclinical depression, supporting dissemination of digital CBT-I to promote youth sleep and mental health. Trial registration: ClinicalTrials.gov NCT04069247.