The Impact of Dexamphetamine Treatment for Obesity on Executive Function: A Double-Blind Randomised Controlled Pilot Study

Abstract

Background: Amphetamines increase dopamine levels in mid-brain regions which, in turn, impact top-down executive function. Repeated exposure is linked to substance use disorders. Nonetheless, amphetamines are used to manage attention-deficit/hyperactivity disorder (ADHD) and eating-related disorders. In ADHD, amphetamines upregulate a system characterised by low dopaminergic tone, assisting to improve executive function. A similar process might be at play with eating disorders; however, the effect of amphetamine treatment on executive function in this case has not been thoroughly considered. Methods: Participants (N = 52, Mage = 47.06, SD = 12.29) with a body mass index of 25–60 were randomised to treatment (6-week dexamphetamine titration) or control (placebo) groups. They completed an executive function measure—Barkley Deficits in Executive Functioning Scale (BDEFS-SF)—and response inhibition task—Stop-Signal Task (SST)—at Baseline, throughout titration, at Maintenance, and at Follow-up. Mixed effects models examined whether BDEFS-SF score or the SST variable, stop-signal reaction time (SSRT), changed across sessions as a function of treatment. Results: There was no effect of group (p = 0.440), but an effect of session (p = 0.024) on BDEFS-SF, with scores at Time 2 (p = 0.011, 95% CI [0.47, 3.49]) and Maintenance (p = 0.022, 95% CI [−4.89, −0.39]), respectively, higher and lower than other timepoints. There was no group by session interaction (p = 0.659). R2 (conditional) = 0.74; ICC = 0.73. There was an effect of group (p = 0.039) and session (p < 0.001) on SSRT, but no interaction (p = 0.707). Baseline SSRT was significantly longer than the mean of all subsequent timepoints (p < 0.001, 95% CI [16.29, 33.84]). R2 (conditional) = 0.47; ICC = 0.39. Conclusions: There was no discernible impact of amphetamine treatment for obesity on executive function. Our results suggest some variation related to sample size and/or practice effects. Thus, while treatment appears unlikely to render individuals susceptible to substance use disorders, parallels with ADHD might be overstated.