A randomized controlled trial of a therapist-guided online intervention for depressed adults and its utility as an adjunctive to antidepressants and psychotherapy.

Background: Internet-based interventions (IBIs) are a low-threshold treatment for individuals with depression. However, comparisons of IBI against unstandardized care-as-usual (CAU) are scarce. Moreover, little evidence is available if IBI has an add-on effect for individuals already receiving an evidence-based treatment such as antidepressants and/or psychotherapy.

Method: This parallel, two-arm RCT (1:1 allocation ratio, simple randomization) examines the effectiveness of a therapist-guided cognitive-behavioral IBI compared to unstandardized CAU in a self-selected sample of adults (≥ 18 years). Eligible individuals reported (a) mild (BDI-II score ≥ 14) to moderately severe (PHQ-9 ≤ 19) symptoms of depression, (b) no acute suicidal ideations, (c) no acute or lifetime (hypo-)mania and/or symptoms of psychosis. We assigned eligible individuals to an intervention (INT) arm or an unstandardized CAU-arm (i.e., we imposed no restrictions on what individuals were allowed to do in the 8-week waiting period). Individuals in the INT-arm got access to a 7-module CBT-based IBI. The primary endpoint is depressive symptom load 9 to 11 weeks after randomization. Secondary endpoints included anxiety, self-efficacy, and perceived social support. We report effects for the entire sample (N = 1899), as well as for individuals using the IBI as a stand-alone intervention (n = 1408) or as an add-on to antidepressants (n = 367), psychotherapy (n = 73), or antidepressants and psychotherapy (n = 51). Patients entered the trial with these concurrent treatments (i.e., they were not randomly assigned).

Results: Concerning all randomized individuals, 62.5% of individuals in the INT-arm accessed all treatment modules within 11 weeks. Individuals assigned to the INT-arm reported significantly lower depressive symptoms (PHQ-9: - 2.5, 95% CI [- 2.9, - 2.0], d =  - 0.7; BDI-II: - 5.3, 95% CI [- 6.5, - 4.1], d =  - 0.8) and higher rates of  ≥ 50% symptom improvements (PHQ-9: 38.5% vs. 14.3%; BDI-II: 44.6% vs. 14.8%) compared to individuals assigned to the CAU-arm. Secondary outcomes also favored INT over CAU, with effect sizes ranging from |d|= 0.18 (social support) to 0.62 (anxiety). Rates of deterioration (PHQ-9: 4.1%; BDI-II: 3.4%) and self-reported side effects (10.5%) were low in the INT-arm. Similar patterns emerged for all strata. However, the between-arm differences failed to reach significance within the strata of individuals using the IBI as an add-on to psychotherapy.

Conclusion: Our results show that providing interested adults access to the therapist-guided, cognitive-behavioral IBI under investigation is associated with improved mental health outcomes, whether individuals use the IBI as a stand-alone or add-on intervention to another evidence-based treatment. This finding aligns with available studies indicating that IBIs should be considered a low-threshold treatment option for individuals with depression.

Trial registration: The trial was registered at the Deutsches Studienregister (Trial-Registriation Number/DRKS-ID: DRKS00021106, Date: 25.06.2020).