February 10, 2015

How an ADHD Drug Works to Combat Binge-Eating

Maria Raquel Cochez (Wikimedia Commons)
Last Friday, the U.S. Food & Drug Administration approved the use of lisdexamfetamine dimesylate for treatment of binge-eating disorder. Licensed under the brand name Vyvanse, lisdexamfetamine is the first and only FDA-approved medication for this condition.

But Vyvanse has already been on the market since 2007 for once-daily usage in attention deficit hyperactivity disorder (ADHD) in children and adults.

How does this drug act on two seemingly distinct conditions?

What is binge-eating disorder?

When we hear the term “binge,” many of us associate it with subsequent purging, as seen in bulimia. Binge-eating disorder, or BED, however, differs in that individuals do not attempt to eliminate their food after a bingeing episode—despite the unbearable shame many often feel afterward.

Global Reactions (Flickr)
BED received its own recognition in 2013 with the release of the DSM-5. Criteria for BED include recurrent episodes (at least once per week for three months) of eating large amounts of food in a short period of time, often accompanied by a sense of no self-control. Before eating, the individual may not have even felt physically hungry, yet will continue only until they feel uncomfortably full. Disgust, guilt, and depression are common feelings after bingeing.

Those with BED often have other psychiatric comorbidities, including major depressive disorder, bipolar disorder, substance abuse, or anxiety disorder. Recent research suggests that those with BED, in general, have lower self-esteem, unhealthy eating patterns, and overall body dissatisfaction. As such, many clinicians refer to binge-eating as an “expressive disorder,” or one that is only expressed as a result of deeper psychological problems.

On Tuesday, ‘90s tennis star Monica Seles opened up to Good Morning America about her decade-long struggle with BED. “For me, when I was in stressful situations on the tennis court or in my personal life, I would start my binge eating,” Seles said. “My trigger foods were pretzels, potato chips—and I would do it alone because I was so ashamed.”

The treatment trials

Lisdexamfetamine’s efficacy in treating BED was demonstrated in two clinical trials of 724 adults with moderate-to-severe binge-eating disorder. The most recent study, published January 14 in JAMA Psychiatry, tracked roughly 260 patients with BED for 14 weeks.

Lisdexamfetamine chemical structure. Jü (Wikimedia Commons)
Participants were between 18 and 55 years of age and had no other psychiatric disorders (notably, no bulimia, anorexia, or ADHD). For 11 weeks, participants were divided into four treatment groups. One group received 30 mg of lisdexamfetamine daily. Two other groups started with 30 mg, but increased to 50 mg or 70 mg after three weeks. The fourth group received placebo.

While only 21% of participants on placebo achieved a binge-free month when assessed in the final few weeks of the study, 50% of those on the highest dosage (70 mg) experienced no binge-eating episodes during this period. Importantly, the safety parameters examined—including changes in blood pressure, heart rate, and other side-effects—were consistent with previous findings in adults taking lisdexamfetamine for ADHD.

“Ask your doctor if Vyvanse is right for you”

Current models suggest that ADHD is associated with impaired neurotransmitter release in several key brain areas. Specifically, reduced levels of dopamine (in the mesocorticolimbic projection) and norepinephrine (locus coeruleus and prefrontal cortex) are most commonly associated with the disorder. These areas modulate control of behavior, motivation, and perception of reward.

Vyvanse tablets, 30 mg. Sardaukar Blackfang (Wikimedia Commons)
Lisdexamfetamine is a central nervous system stimulant prodrug, meaning that it's inactive when you ingest it, but then converts to an active form through normal metabolism. In this case, lisdexamfetamine is broken down into methylphenidate and amphetamine, which increase neurotransmitter activity in affected brain regions. Psychostimulants (like this medication) show improvement of ADHD symptoms in roughly 70% of individuals, including increased motivation to perform tasks and increased wakefulness.

A recent meta-analysis suggests that psychostimulants may also be useful for treating binge-eating for three reasons. First, the drug’s modulation of dopamine and norepinephrine may also impact eating behavior and reward. Second, many stimulants are associated with weight loss. And third, large studies have shown a comorbid relationship between BED and ADHD in adolescents and adults.

Indeed, research suggests that binge-eating is influenced by an abnormally strong response to the hedonic properties of food (or, in other words, why we find sweet and fatty foods so tasty). Using PET scans, a 2011 study by the U.S. Department of Energy’s Brookhaven National Laboratory reported that, compared to obese controls, binge-eaters show a significantly higher spike in dopamine levels in response to the sight or smell of their favorite foods.

Major dopamine pathways of the brain (purple). NIDA (Wikimedia Commons)

During drug metabolism, the amphetamine component of lisdexamfetamine works to increase the release of both dopamine and norepinephrine in key brain regions related to reward. In short, those with binge-eating disorder may be able to get their “dopamine high” from lisdexamfetamine instead of food.

While lisdexamfetamine may be a promising option for patients with BED, it is not without risk. For one, the impulsivity associated with eating disorders may also predispose one for substance abuse. Moreover, some individuals with eating disorders may be more prone to certain cardiac problems and should not take a stimulant medication. Other patients may find that a psychological intervention, such as cognitive behavioral therapy, is more effective than a drug for them.

Regardless, the use of an ADHD drug for treating a condition like binge-eating demonstrates one of the most fascinating aspects of medicine: although the biological mechanisms may be the same, physical and psychological problems can manifest themselves in very, very different ways.

Originally published at The Conversation.The Conversation

1 comment:

  1. Wow, thanks for restoring my faith in health-science journalism. It's been a rough day in the NYTimes echo chamber ...aka Twitter


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