EMOTIONAL DYSREGULATION SYMPTOM OUTCOMES IN ADULTS WITH ADHD TREATED WITH CENTANAFADINE: A POOLED POST HOC ANALYSIS OF TWO PHASE 3 TRIALS

Background

Attention-deficit/hyperactivity disorder (ADHD) in adults frequently includes symptoms of emotional dysregulation, such as affective lability, emotional overreactivity, frustration tolerance, and anger outbursts. This pooled post hoc analysis of two phase 3 trials evaluated the effect of centanafadine (CTN)—a norepinephrine, dopamine, serotonin reuptake inhibitor—on patient-reported assessment of emotional dysregulation using the adult ADHD Self-Report Scale (ASRS) Expanded Version after 6 weeks of treatment in adults with ADHD.

Methods

Data from two identically designed phase 3 trials were pooled. Eligible patients (aged 18–55 years) with a primary ADHD diagnosis per DSM-5 were randomized to receive CTN 200 or 400mg/day or placebo. Exploratory endpoints included changes from baseline in the Emotional Dyscontrol (ED) subscale score and individual ED line items from the ASRS Expanded Version at Week 6. The ASRS Expanded Version is a validated, self-administered questionnaire that includes 4 items assessing aspects of emotional dysregulation, with responses rated on a 5-point Likert scale (0=never to 4=very often). Endpoints were analyzed using a mixed-effects model for repeated measure without adjusting for multiplicity.

Results

A total of 744 adults were included in the efficacy sample (CTN 200mg, n=242; 400mg, n=241; placebo, n=261). At Week 6, adults treated with CTN reported improvements from baseline in the ASRS E D subscale compared with placebo, reflecting reductions in the frequency of specific patient-reported emotional dysregulation dimensions assessed by the scale (200mg: −0.9, P=0.0023; 400mg: −0.9, P=0.0006). Effect sizes (Cohen’s D) for the ASRS ED subscale were 0.27 for CTN 200mg and 0.31 for 400mg. Consistent with the subscale-level findings, improvements from baseline vs placebo were observed across individual Aitems atems at Week 6, including those related to affective lability, emotional overreactivity, and anger outbursts.

Conclusions

In this pooled post hoc analysis, CTN was associated with improvements in patient-reported emotional dysregulation in adults with ADHD, as assessed by the ASRS Expanded Version. Improvements were observed across ED items capturing externally expressed, behavioral dimensions of emotional dysregulation, including affective lability, emotional over reactivity, and anger outbursts, with improvements of similar magnitude to those observed for core ADHD symptom domains.