05. Prospects for New Drugs To Treat Binge Eating Disorder: Insights From Psychopathology and Neuropharmacology

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Is binge eating disorder more like an addictive disorder or an impulse control disorder? Would you expect medications for addictions or medications for impulse control issues like ADHD to help patients with binge eating disorder?

Hi! Jim Phelps for the Psychopharmacology Institute. Here, we’ll look at a review from the Journal of Psychopharmacology that provides some evidence regarding these questions and examines pharmaceutical treatment options. Spoiler alert! Only a few survived scrutiny. Before going further, let’s review the DSM criteria for binge eating disorder. It’s distressing. There is a lack of control of eating leading to 1 or more days a week of the following 5 problems, and a person must have 3 for diagnosis: Eating large amounts rapidly to the point of discomfort and/or, number 4, eating alone because of embarrassment and, fifth, feeling disgusted or guilty afterward. So, eating large amounts, rapidly, discomfort, alone, disgusted. This has to go on for 3 months or more and is not accompanied by compensatory purging, fasting, or exercise or otherwise is associated with anorexia or bulimia.

Now, is binge eating disorder more like an addictive disorder, an impulse control disorder, or a hypothalamic regulatory problem? The authors of this new review note that drugs that are approved to treat substance use disorders, like acamprosate and naltrexone, have not shown clear evidence of efficacy for binge eating disorder. They also assert that binge eating disorder is not a failure of the hypothalamic regulation of food intake, pointing at the failure of anti-obesity drugs to show efficacy in BED.

The authors don’t mention research that suggests that glucagon-like peptide 1 receptor agonists, such as semaglutide and numerous others, could be candidates for study, as has been suggested by another research group. Instead, Drs. Heal and Smith focused on medications that work for ADHD, like dextroamphetamine, because, in their view, the central problem in binge eating is impulse control. They cite studies showing that people with BED, binge eating disorder, have enhanced discounting—a preference for smaller immediate gains at the cost of larger delayed gains.

Remember this from economics: The willingness to take a smaller amount of money now compared with a larger amount in 2 months? It’s like the old marshmallow study, the one in which a series of 4-year-olds were offered a marshmallow now or 2 marshmallows if they could wait 5 minutes and not eat the first one. They were left alone in the room with the marshmallow. I’ll link a video and the references here and here at the Psychopharmacology Institute. They’re very cute.

The idea is that people who meet criteria for binge eating disorder or ADHD have enhanced discounting. They’re less inclined to wait for the second marshmallow. Doesn’t this suggest to you that a cognitive and behavioral approach would be a good idea? But this being a pharmacologic review, Drs. Heal and Smith proceed into considerable detail regarding 15 candidate medications for BED that target impulsivity and weight loss.

The studies point mainly at lisdexamfetamine. Everything else either doesn’t work, has less evidence for efficacy, or production was discontinued after a lack of FDA approval. Lisdexamfetamine has a lysine attached to slow its metabolism and prevent snorting. Heal and Smith, whose company does consulting work for large pharmaceutical companies, don’t mention a recent randomized trial of methylphenidate for binge eating disorder. In that small study with 22 people in the stimulant group and 27 people in the comparison group, CBT and methylphenidate were equal in efficacy for binge episode frequency. Methylphenidate was associated with more weight loss. Well, at least then there’s a study to suggest that stimulants as a class have efficacy in binge eating disorder.

Nevertheless, Heal and Smith’s article does provide a look at medications that could target both impulse control and weight loss, and here are quick details for 9 of them.

Phentermine differs from dextroamphetamine by a single methyl group. It has a powerful dopaminergic effect, and there is a 1999 study in ADHD that showed benefit. It’s still used for weight loss, but it hasn’t been studied for BED except in combination with other drugs.

Modafinil is a stimulant, but it’s not clearly dopaminergic. One randomized trial has tested modafinil in binge eating disorder but with only 30 patients in each group. The lack of efficacy relative to placebo could’ve been because the study was underpowered. There were some positives among the secondary analyses.

Bupropion has been evaluated in BED, where it did produce weight loss—especially when given with naloxone—but in one study, it didn’t reduce food craving or binge frequency.

Atomoxetine has been evaluated in one small BED trial, where it produced modest improvements in the craving part but clinically insignificant weight loss.

Topiramate: Its adverse effects were just so bad—mainly cognitive impairment—that all studies in obesity and type 2 diabetes have been halted.

Rimonabant is a cannabinoid antagonist and inverse agonist that was withdrawn from FDA consideration back in 2007. It did reduce weight but had no effect on bingeing.

Acamprosate is useful for alcohol dependence, but it doesn’t have any effect on bingeing. For naltrexone, there are no trials in binge eating disorder of naltrexone as monotherapy. And samidorphan is dismissed as ineffective in this review, although there is a larger literature on opiates in eating disorders that isn’t examined here.

In summary, for the treatment of binge eating, CBT works and so does dextroamphetamine and perhaps stimulants as a class. For more on this, some balance would be achieved by looking at some literature on CBT for BED, which I’ve linked to in the references.

Abstract

Background: Binge-eating disorder (BED) is a common psychiatric condition with adverse psychological and metabolic consequences. Lisdexamfetamine (LDX) is the only approved BED drug treatment. New drugs to treat BED are urgently needed.

Methods: A comprehensive review of published psychopathological, pharmacological and clinical findings. Results: The evidence supports the hypothesis that BED is an impulse control disorder with similarities to ADHD, including responsiveness to catecholaminergic drugs, for example LDX and dasotraline. The target product profile (TPP) of the ideal BED drug combines treating the psychopathological drivers of the disorder with an independent weight-loss effect. Drugs with proven efficacy in BED have a common pharmacology; they potentiate central noradrenergic and dopaminergic neurotransmission. Because of the overlap between pharmacotherapy in attention deficit hyperactivity disorder (ADHD) and BED, drug-candidates from diverse pharmacological classes, which have already failed in ADHD would also be predicted to fail if tested in BED. The failure in BED trials of drugs with diverse pharmacological mechanisms indicates many possible avenues for drug discovery can probably be discounted.

Conclusions: (1) The efficacy of drugs for BED is dependent on reducing its core psychopathologies of impulsivity, compulsivity and perseveration and by increasing cognitive control of eating. (2) The analysis revealed a large number of pharmacological mechanisms are unlikely to be productive in the search for effective new BED drugs. (3) The most promising areas for new treatments for BED are drugs, which augment noradrenergic and dopaminergic neurotransmission and/or those which are effective in ADHD.

Reference

Heal, D. J., & Smith, S. L. (2021). Prospects for new drugs to treat binge-eating disorder: Insights from psychopathology and neuropharmacology. Journal of Psychopharmacology, 026988112110324. 

Related References

• Kirschenbaum, D. S., & Krawczyk, R. (2018). The food addiction construct may do more harm than good: Weight controllers are athletes, not addicts. Childhood Obesity, 14(4), 227–236. 
• McElroy, S. L., Mori, N., Guerdjikova, A. I., & Keck Jr, P. E. (2018). Would glucagon-like peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature. Medical Hypotheses, 111, 90-93.
• The Marshmallow Study. https://en.wikipedia.org/wiki/Stanford_marshmallow_experiment
• The Marshmallow Study: Videotape Footage — https://www.youtube.com/watch?v=QX_oy9614HQ
• Quilty, L. C., Allen, T. A., Davis, C., Knyahnytska, Y., & Kaplan, A. S. (2019). A randomized comparison of long acting methylphenidate and cognitive behavioral therapy in the treatment of binge eating disorder. Psychiatry Research, 273, 467–474. 
• Grilo, C. M., Masheb, R. M., & Wilson, G. T. (2005). Efficacy of cognitive behavioral therapy and fluoxetine for the treatment of binge eating disorder: a randomized double-blind placebo-controlled comparison. Biological Psychiatry, 57(3), 301-309.
• American Psychological Association. Cognitive Behavioral Therapy for Binge Eating Disorder. https://div12.org/treatment/cognitive-behavioral-therapy-for-binge-eating-disorder/