Secondary analyses of sex differences in attention improvements across three clinical trials of a digital therapeutic in children, adolescents, and adults with ADHD.

Background: Attention-deficit/hyperactivity disorder (ADHD) remains underdiagnosed and undertreated in girls. Inattentive symptoms, often predominant in girls with ADHD, represent a key driver of impairment and often persist into adulthood. AKL-T01 is a regulated digital therapeutic targeting inattention. We examined potential sex differences in the efficacy of AKL-T01 in three separate trials for 1) children, 2) adolescents, and 3) adults.

Methods: We conducted secondary analyses of clinical outcomes by sex in three AKL-T01 randomized clinical trials in ADHD (n1 = 180 children 30.6% female, M(SD) age = 9.71 (1.32); n2 = 146 adolescents; 41.1% female, M(SD) age = 14.34 (1.26); n3 = 153 adults; 69.9% female, M(SD) age = 39.86 (12.84)). Active treatment participants used AKL-T01 for 25 min/day over 4-6 weeks. Primary outcomes included change in attention on the Test of Variables of Attention (TOVA) and symptom change on the clinician-rated ADHD Rating Scale (ADHD-RS). To evaluate study hypotheses, we conducted a series of robust linear regressions of TOVA and ADHD-RS change scores by sex, adjusting for baseline scores.

Results: In children, girls demonstrated greater improvement in objective attention relative to boys following AKL-T01 (TOVA Attentional Composite Score; Cohen's d = .36 and Reaction Time Mean Half; Cohen's d = .54), but no significant sex differences in ADHD rating scale change. We did not observe significant sex differences in outcomes in the adolescent or adult trials. Limitations include binary sex categorization and slight study design variation across the three samples.

Conclusion: AKL-T01 might notably improve attentional functioning in girls with ADHD relative to boys. Objective attention measures may be particularly important in the assessment of attentional improvement in childhood, given known gender biases in ADHD symptom reporting. We emphasize the importance of considering sex and gender-specific factors in ADHD treatment evaluation.

Trial Registrations: STARS ADHD CHILD: ClinicalTrials.gov ID NCT03649074; STARS ADHD ADOLESCENT: ClinicalTrials.gov ID NCT04897074; STARS ADHD ADULT: ClinicalTrials.gov ID NCT05183919.