Functional Connectivity Mechanisms Underlying Symptom Reduction Following Lisdexamfetamine Treatment in Binge-Eating Disorder: A Clinical Trial

BACKGROUND: Speculation exists as to whether lisdexamfetamine dimesylate (LDX) acts on the functional connectivity (FC) of brain networks that modulate appetite, reward, or inhibitory control in binge -eating disorder (BED). Better insights into its action may help guide the development of more targeted therapeutics and identify who will benefit most from this medication. Here, we use a comprehensive data -driven approach to investigate the brain FC changes that underlie the therapeutic action of LDX in patients with BED. METHODS: Forty-six participants with moderate to severe BED received LDX titrated to 50 or 70 mg for an 8 -week period. Twenty age -matched healthy control participants were also recruited. Resting -state functional magnetic resonance imaging was used to probe changes in brain FC pre- and post treatment and correlated with change in clinical measures. RESULTS: Ninety-seven percent of trial completers (n = 31) experienced remission or a reduction to mild BED during the 8 -week LDX trial. Widespread neural FC changes occurred, with changes in default mode to limbic, executive control to subcortical, and default mode to executive control networks associated with improvements in clinical outcomes. These connections were not distinct from control participants at pretreatment but were different from control participants following LDX treatment. Pretreatment connectivity did not predict treatment response. CONCLUSIONS: FC between networks associated with self -referential processing, executive function, and reward seem to underlie the therapeutic effect of LDX in BED. This suggests that LDX activates change via multiple systems, with most changes in compensatory networks rather than in those characterizing the BED diagnosis.