Digital Intervention for Cognitive Deficits in Major Depression: A Randomized Controlled Trial to Assess Efficacy and Safety in Adults.

ABSTRACT

OBJECTIVE: The authors evaluated AKL-T03, an investigational digital intervention delivered through a video game-based interface, designed to target the fronto-parietal network to enhance functional domains for attentional control. AKL-T03 was tested in adult patients with major depressive disorder and a demonstrated cognitive impairment at baseline. METHODS: Adults ages 25-55 years on a stable antidepressant medication regimen with residual mild to moderate depression and an objective impairment in cognition (as measured using the symbol coding test) were enrolled in a double-blind randomized controlled study. Participants were randomized either to AKL-T03 or to an expectation-matched digital control intervention. Participants were assessed at baseline and after completion of their 6-week at-home intervention. The primary outcome measure was improvement in sustained attention, as measured by the Test of Variables of Attention (TOVA). RESULTS: AKL-T03 (N=37) showed a statistically significant medium-effect-size improvement in sustained attention compared with the control intervention on the TOVA primary outcome (N=37) (partial eta-squared=0.11). Additionally, a composite score derived from all cognitive measures demonstrated significant improvement with AKL-T03 over the control intervention. Individual secondary and exploratory endpoints did not demonstrate statistically significant between-group differences. No serious adverse events were reported, and two patients (5.5%) in the AKL-T03 group reported an intervention-related adverse event (headache). CONCLUSIONS: Treatment with AKL-T03 resulted in significant improvement in sustained attention, as well as in cognitive functioning as a whole, compared with a control intervention. AKL-T03 is a safe digital intervention that is effective in the treatment of cognitive impairment associated with major depression. Further research will be needed to understand the clinical consequences of this treatment-induced change.