The effects of lisdexamfetamine dimesylate on eating behaviour and homeostatic, reward and cognitive processes in women with binge-eating symptoms: an experimental medicine study

Abstract

Lisdexamfetamine dimesylate (LDX) is the only drug currently approved by the FDA for the treatment of Binge-Eating Disorder (BED), but little is known about the behavioural mechanisms that underpin the efficacy of LDX in treating BED. We examined the behavioural and neural effects of an acute dose of LDX (50 mg) in 22 women with binge-eating symptomatology using a randomised, crossover, double-blind, placebo-controlled experimental medicine design. LDX reduced self-reported appetite ratings and intake of both a pasta meal and a palatable cookie snack. LDX also decreased the eating rate of pasta but not of cookies and reduced self-reported liking ratings for pasta at the end of the meal. When viewing food pictures during an fMRI scan, LDX reduced activity bilaterally in the thalamus. LDX enhanced sustained attention and reduced impulsive responding in a continuous performance task but had no effect on emotional bias or working memory. These results suggest the observed effects of LDX on food intake (and by implication the efficacy of LDX in treating BED) may be related to the actions of the drug to enhance satiety, reduce food-related reward responding when full and/or increase cognitive control. Novel pharmacotherapies for BED might be most effective if they have a broad spectrum of effects on appetite, reward and cognition.

Potential Biological Markers and Treatment Implications for Binge Eating Disorder and Behavioral Addictions

“…Likewise, reductions in vmPFC correlated with reductions in binge eating behaviors. Other studies have associated lisdexamfetamine with reduced activity bilaterally in the thalamus in individuals with BED when viewing food pictures [ 138 ]. Likewise, lisdexamfetamine appears to reduce motor impulsivity, but does not appear to have an effect on working memory or emotional bias [ 138 ].…”

“…Other studies have associated lisdexamfetamine with reduced activity bilaterally in the thalamus in individuals with BED when viewing food pictures [ 138 ]. Likewise, lisdexamfetamine appears to reduce motor impulsivity, but does not appear to have an effect on working memory or emotional bias [ 138 ]. Lisdexamfetamine is currently the only drug with formal regulatory approval for treating BED.…”

Is there a role for higher cognitive processes in the development of obesity in humans?

“…LDX has been reported to improve inhibitory control in women with binge eating symptoms and, alongside this improvement in cognition, to reduce food intake [ 120 ]. The effects of LDX and other cognitive enhancers on weight loss/prevention of weight gain could be examined in randomized controlled studies [ 121 , 122 ]. Interestingly, ADHD is associated with disinhibited eating and obesity [ 123 , 124 ] and this relationship is related to deficits in attention and cognitive control [ 124 , 125 ].…”

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

“…Lisdexamfetamine dimesylate (LDX) is currently the only drug approved for the treatment of moderate to severe BED. It is a prodrug of d-amphetamine that significantly reduces intake of highly palatable food ( 4 ), BE frequency, and impulsivity ( 5 , 6 , 7 , 8 ) in people with BED. Despite its demonstrated efficacy in reducing BE episodes, there is speculation whether BED occurs predominantly via altering appetite, reward sensitivity, or cognitive control processes ( 9 ).…”

“…One study reported reductions in ventromedial prefrontal cortex activation that were correlated with BE symptom reduction after 12 weeks of LDX ( 10 ). The other study reported reduced bilateral thalamic activation after an acute 50 mg dose of LDX administered to 22 women in a randomized, crossover, placebo-controlled design ( 4 ). However, both studies used task-evoked food stimuli designs, which examine LDX-related changes specifically related to the salience of food cues but not across a broader context.…”