Binge-eating episodes are defined as the consumption of an objectively large amount of food while experiencing a loss of control over eating [1]. In children, accurately quantifying a “large amount of food” is problematic because intermittent overconsumption is a normal behavior in growing youth [2]. Instead, many researchers measure ‘loss of control eating’ (LOC-E) rather than binge eating when studying disordered eating in youth. Notably, 9–30% of 9–13-year-old youth experience LOC-E, though only 1/3 to 1/2 of these children present with these symptoms after 5 years [3]. In addition to a high prevalence rate, LOC-E in middle childhood (8–12 years old) also robustly predicts the later development of partial or full-syndrome binge eating disorder (BED) [4, 5, 6] and excessive weight gain in children at high risk for adult obesity [4, 7]. Based on these factors, LOC-E has been proposed as a relevant target for preventive interventions [8].
To develop treatments for LOC-E, it is important to understand the underlying disease processes and mechanisms. Recent evidence suggests that neurocognitive predisposing factors (e.g., impulsivity and dysfunctional reward processing) are relevant in the pathogenesis of LOC-E. First, there is evidence that children (8–14 years old) with Attention Deficit/Hyperactivity Disorder (ADHD) have 12 times the risk of experiencing LOC-E compared to healthy controls [9]. This study also found that children with LOC-E are more likely to exhibit high impulsivity on a neurobehavioral task (Go/No Go) and parent-rated scale compared to healthy controls. Another study used a delay of gratification task (DoGT) in children with ADHD or LOC-E, comorbid diagnoses (ADHD and LOC-E), and healthy controls [10]. They found that children with ADHD and comorbid diagnoses had significantly higher risk of eating prematurely during the DoGT compared to children with only LOC-E or healthy controls. Moreover, the children with comorbid diagnoses were most likely to worry about losing control over eating during the task. These findings suggest that a lack of behavioral inhibition (to food reward) in children with ADHD is a relevant factor in the drive to eat prematurely [10].
Neurobiological studies have shown that the relationship between ADHD and binge eating (in adults) is largely explained by shared genetic risk factors [11]; however, there are also non-shared environmental factors that explain the covariance [8]. In a neuroimaging study, Murray et al. [12] found that children with early onset BED have underlying dysconnectivity between the brain’s inhibitory network and reward system. These findings suggest that poor connectivity between reward and impulse-control-related neural pathways underlie some children’s inability to regulate their drive to eat. Importantly, similar perturbations in functional connectivity have been illustrated in key nodes of the inhibitory control network in those with ADHD [13] – suggesting similar underlying mechanisms.
Recent research has started to delineate not only the association between ADHD and LOC-E, but also the directionality of the relationship. A large longitudinal study by Sonneville et al. [14] showed that ADHD in children (mean = 11.7 years old) predicted binge eating in mid-adolescence (14–16 years old) via late childhood overeating and early adolescent ‘strong desire for food’. Relatedly, emerging longitudinal data are supporting a causal role of ADHD in contributing to excessive weight gain [15].
Considering this evidence, it is relevant to examine whether modifying neurocognitive symptoms, such as impulsivity, influences LOC-E and the subsequent development of eating disorders and obesity. Stimulant medication is an example of a treatment that could modify these neurocognitive symptoms, and in doing so, potentially effect change in symptoms of LOC-E. Robust evidence supports stimulants as an efficacious treatment for impulsivity in youth with ADHD [16]; however, studies have not explored the effect of stimulants on LOC-E in children. Relevantly though, there is evidence that stimulants improve symptoms of binge eating in adults, and also, that stimulants may mediate this effect by improving impulsivity [17, 18, 19]. Notably, the stimulant lisdexamfetamine (LDX) received regulatory approval for the treatment of moderate to severe BED in adults based on one 11-week Phase 2 dose-finding study and two identically designed 12-week Phase 3 dose optimization studies [19, 20, 21].
In addition to clinical trial evidence, there are also neurobiological explanations that support the use of stimulants as a treatment for LOC-E [22, 23]. For example, the explanatory models for ADHD suggest that deficits in dopamine function, such as reduced dopamine neuronal tone affect executive functioning and reward processing [24]. Similarly, disordered eating, such as binge eating has been associated with lower dopamine (and norepinephrine) metabolite levels in the cerebrospinal fluid [25, 26]. In sum, for ADHD and eating disorders, there is evidence of altered dopaminergic tone, presumably lower intrasynaptic dopamine, and since stimulant medications increase intrasynaptic dopamine and norepinephrine levels in striatal and cortical brain regions, a plausible explanatory model supports the use of stimulant medication for LOC-E.
As further support for exploring the effect of stimulants on LOC-E in youth, retrospective and cross-sectional data suggests that children with ADHD who had been treated with stimulants had less odds of obesity compared to those who were not medicated [27]. Importantly, that research does not elucidate whether stimulants were associated with lower obesity rates because they lessened symptoms of LOC-E, or alternatively, whether a different mechanism mediated the apparent effect on obesity (e.g., appetite suppression independent of effect on disordered eating).
In sum, though stimulants warrant investigation as a treatment for LOC-E in youth, no studies have prospectively examined the effect of stimulants on this form of disordered eating. To gather pilot data, we aim to measure prospective, observational outcomes in a clinical setting to examine the effect of stimulant initiation on LOC-E in children with comorbid ADHD and LOC-E. We will also collect exploratory secondary outcomes to measure eating-related cognitions and emotions, ADHD symptom severity, parental LOC-E, impulsivity and reward sensitivity, and anxiety/mood symptoms. Given the observational design, we will not generate a priori hypotheses.