Video Game Intervention AKL-T03 Improves Attention, Cognition in Adults with Depression

Richard S.E. Keefe, PhD

Investigational digital therapeutic AKL-T03 provided significant improvement to the sustained attention and overall cognition of patients with major depression, according to new trial data.

In new findings assessing the clinically-used digital video game software as a therapeutic for attention and related attentional control processes, a team of US-based investigators found the novel intervention may be beneficial, safe and more accessible for patients struggling to resolve depression-associated cognitive dysfunction.

Led by Richard S.E. Keefe, PhD, of the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center, investigators sought to evaluate AKL-T03 for adults with depression and cognitive impairment versus an educational-styled digital control intervention. AKL-T03 is actually an adapted product of the AKL-T01—the latter sharing proprietary algorithms with the former, but having been developed with a video game appearance deemed more appropriate for children.

“The underlying pathophysiology of cognitive impairment in patients with major depression appears to be associated with inefficient functioning of the fronto-parietal cognitive control networks, which have a high degree of connectivity across brain regions and can rapidly modify functional connections in response to changing internal and environmental demands,” investigators wrote. “Digital interventions that can adapt the difficulty of a cognitive exercise based on the user’s performance level may hold promise as a personalized tool to target the cognitive impairments of major depression.”

Keefe and colleagues randomized adults aged 25-55 years old with residual mild to moderate depression and objective cognition impairment per symbol coding tests to either AKL-T03 or an expectation-matched digital control intervention. Their primary outcome was improvement in sustained attention per Test of Variables of Attention (TOVA), a validated computerized continuous performance test that gauges patients’ attention and inhibitory control.

Patients were assessed at baseline and after completing their 6-week at-home intervention. Eligible patients were diagnosed with major depressive disorder, scored between 14 and 22 on the 17-item Hamilton Depression Rating Scale (HAM-D) during the screening phase, were on antidepressant medication for ≥8 weeks prior to screening, and on a stable dosage for ≥4 weeks.

Patients with significant comorbid psychiatric diagnoses and active suicide risk or ideation were excluded from the trial.

The final population included 74 patients split 1:1 to AKL-T03 (n = 37) or control (n = 37). Patients receiving the video game software as intervention showed a statistically significant improvement in sustained attention per TOVA versus control (F, 8.550; df, 1-69; P = .005). A composite score derived from primary and secondary outcome metrics showed AKL-T03 provided significant improvement in patient cognition.

Investigators observed no serious adverse events among treated patients with depression; 2 (5.5%) patients in the AKL-T03 group reported intervention-related headaches.

Keefe and colleagues concluded the investigative adult-based digital software provided significant, safe and tolerable improvement in sustained attention and cognitive functioning for patients with depression. They called for further research into the clinical consequences of changes induced by the intervention.

“AKL-T03 shows promise for reducing cognitive impairment during a current episode of depression,” they wrote. “Further research looking at longitudinal data and durability of effect is needed to confirm the hypothesis that cognitive improvements may have an impact on functional outcomes and potentially on future relapses.”

The study, “Digital Intervention for Cognitive Deficits in Major Depression: A Randomized Controlled Trial to Assess Efficacy and Safety in Adults,” was published online in The American Journal of Psychiatry.