<b><i>Introduction:</i></b> The global disease burden of major depressive disorder urgently requires prevention in high-risk individuals, such as recently discovered insomnia subtypes. Previous studies targeting insomnia with fully automated eHealth interventions to prevent depression are inconclusive: dropout was high and likely biased, and depressive symptoms in untreated participants on average improved rather than worsened. <b><i>Objective:</i></b> This randomized controlled trial aimed to efficiently prevent the worsening of depressive symptoms by selecting insomnia subtypes at high risk of depression for internet-based circadian rhythm support (CRS), cognitive behavioral therapy for insomnia (CBT-I), or their combination (CBT-I+CRS), with online therapist guidance to promote adherence. <b><i>Methods:</i></b> Participants with an insomnia disorder subtype conveying an increased risk of depression (<i>n</i> = 132) were randomized to no treatment (NT), CRS, CBT-I, or CBT-I+CRS. The Inventory of Depressive Symptomatology – Self Report (IDS-SR) was self-administered at baseline and at four follow-ups spanning 1 year. <b><i>Results:</i></b> Without treatment, depressive symptoms indeed worsened (<i>d</i> = 0.28, <i>p</i> = 0.041) in high-risk insomnia, but not in a reference group with low-risk insomnia. Therapist-guided CBT-I and CBT-I+CRS reduced IDS-SR ratings across all follow-up assessments (respectively, <i>d</i> = –0.80, <i>p</i> = 0.001; <i>d</i> = –0.95, <i>p</i> &#x3c; 0.001). Only CBT-I+CRS reduced the 1-year incidence of clinically meaningful worsening (<i>p</i> = 0.002). Dropout during therapist-guided interventions was very low (8%) compared to previous automated interventions (57–62%). <b><i>Conclusions:</i></b> The findings tentatively suggest that the efficiency of population-wide preventive strategies could benefit from the possibility to select insomnia subtypes at high risk of developing depression for therapist-guided digital CBT-I+CRS. This treatment may provide effective long-term prevention of worsening of depressive symptoms. <b><i>Trial registration:</i></b> the Netherlands Trial Register (NL7359).

No abstract

No abstract