VYVANSE for Binge Eating: Old Pill, New ‘Disease’

In January, physicians and patients across the U.S. started seeing a new advertising campaign. The glossy ads show a woman hugging her knees and looking worried, as a hamburger and soft drink sit untouched at her feet. Around her swirls a menacing spiral of doughnuts, French fries and other junk food. "Binge eating disorder (BED)," reads the caption. "Identifying and accurately diagnosing adults with BED is the first step to helping them."

This marketing campaign, sponsored by pharmaceutical company Shire PLC, represents one of the latest examples of a particularly insidious drug advertising practice, in which a drug manufacturer spends money promoting "awareness" of a disease. None of these advertising materials mention any drug, but Shire manufactures the only drug that is approved by the Food and Drug Administration (FDA) to treat binge eating: lisdexamfetamine (VYVANSE). This means every new diagnosis of BED brings Shire a potential new customer.

The company stands to make enormous profits from this campaign. But what is good for Shire almost certainly will be harmful for patients. Lisdexamfetamine is a potentially addictive drug that reduces appetite at the expense of raising blood pressure and increasing heart rate. It has been linked to an increased risk of sudden death, stroke and heart attack. So for many patients, being diagnosed with BED will bring them one step closer to a dangerous treatment.

Evolution of an illness

Binge eating, or eating large amounts of food and feeling out of control while doing it, is not a new phenomenon.[1] However, this behavior was not recognized as a distinct medical disorder until 2013, when the Diagnostic and Statistical Manual of Mental Disorders (DSM), which provides standards used by psychiatrists and other physicians to diagnose mental health disorders, was revised to include "binge eating disorder" as a separate diagnosis.[2],[3]

Yet what constitutes binge eating disorder still is not entirely clear. Shire's website describes "[r]egularly eating far more food than most adults would in a similar time period under similar circumstances" and "[f ]eeling that one's eating is out of control during a binge." Eating fast, eating when not hungry, eating in secret and feeling bad about eating are all signs of the disorder, according to the website.[4] Unsurprisingly, this type of overeating and guilt is a common problem, particularly among people who are overweight or obese.[5]

Binge eating behavior and guilty feelings can be successfully treated through behavioral therapy.[6] But many patients who seek treatment for binge eating want to do more than control their behavior and state of mind: They seek to lose weight as well.[7] This has led many doctors and patients to experiment with various drug treatments, without great success.[8]

A new indication for an old pill

The approval of lisdexamfetamine marks the first time the FDA has approved a drug specifically to treat binge eating. Lisdexamfetamine is a type of amphetamine,[9] a class of addictive simulants that have long been known to promote weight loss.[10] Amphetamines were widely consumed for weight loss from the 1940s until the 1970s, when federal narcotic authorities and the FDA introduced stricter prescribing and marketing controls to address the drugs' addiction potential.[11]

Until this year, lisdexamfetamine was FDA-approved only for attention-deficit hyperactivity disorder.[12] Had Shire sought to have this amphetamine approved for weight loss instead of as a "cure" for binge eating, it would have faced significantly greater hurdles. For example, seeking approval of the drug as a weight loss treatment would have required studies that were much larger and at least four times longer than those that tested the drug for binge eating.[13],[14],[15]

Lisdexamfetamine has been linked to sudden death, stroke and heart attack in adults and children.[16] Aware of these potential risks, Shire chose to develop lisdexamfetamine for binge eating disorder, not weight loss.[17] This choice paid off: The FDA allowed Shire to avoid longer-term premarket safety testing and instead perform just 12 weeks of testing in placebo-controlled trials.[18] Shire also was allowed to exclude people with existing cardiovascular problems from clinical testing, making it even less likely that high numbers of cardiovascular side effects would occur during clinical trials and potentially prevent the new indication from being approved.[19] Equally important for Shire, if it had marketed the drug for weight loss, it would have had to compete with a growing number of such drugs, but, for binge eating, it currently has the marketplace to itself.

Lisdexamfetamine did reduce binge eating in clinical trials, at least for the 12 weeks subjects were taking the drug.[20] Also, as might have been expected from an amphetamine, the drug led to short-term weight loss, about 5 or 6 percent of total body weight on average.[21]

But the drug also significantly increased blood pressure and heart rate, factors indicating potentially increased cardiovascular risk.[22] Some subjects taking the drug also experienced fainting and a condition known as Raynaud's phenomenon. This disease of the circulatory system involves temporary interruptions in blood flow, usually to the fingers and toes, leading to sensations of cold or numbness and skin color changes.[23]

These signs and symptoms were troubling to FDA officials, but because the trials were of short duration and enrolled only relatively healthy patients, there were few serious adverse events overall during testing.[24] This made it difficult for FDA officials to draw firm conclusions.[25]

The FDA ultimately approved lisdexamfetamine for the new binge eating use.[26] Shire is not allowed to promote the drug for weight loss.[27] Yet this distinction is likely to mean little in real-world practice, as overweight and obese patients seeking treatment for binge eating generally desire to lose weight and achieve overall health, not simply to control the sense of unhappiness they feel about their behavior.[28]

Advice for patients

Public Citizen's Health Research Group has the same advice for binge eating drugs as it does for pills marketed more explicitly to promote weight loss: Do not use these drugs. Time and again, weight loss drugs have been shown to lack important long-term benefits and carry serious and unpleasant side effects. Marketing these drugs for binge eating does not render these drugs effective and safe for widespread use.[29]

References

[1] Spitzer RL, Stunkard A, Yanovski S, et al. Binge eating disorder should be included in the DSM-IV: A reply to Fairburn et al.'s 'The classification of recurrent overeating: The binge eating disorder proposal.' Int J Eat Disord. 1993;13(2):161-169.

[2] Spitzer R. Nonpurging bulimia nervosa and binge eating disorder. Am J Psychiatry. 1991;148:8.

[3] Amianto F, Ottone L, Abbate Daga G, Fassino S. Binge-eating disorder diagnosis and treatment: A recap in front of DSM-5. BMC Psychiatry. 2015;15:70.

[4] Shire Pharmaceuticals. What B.E.D. looks like in adults. BingeEatingDisorder.com. http://www.bingeeatingdisorder.com/what-is-BED.aspx. Accessed June 3, 2015.

[5] Brownley KA, Peat CM, La Via M, Bulik CM. Pharmacological approaches to the management of binge eating disorder. Drugs. 2015;75:9-32.

[6] Ibid.

[7] Ibid.

[8] Ibid.

[9] Food and Drug Administration. Medical review: Lisdexamfetamine dimesylate (Vyvanse). NDA#: 21-977/S037. Approval date: 1/30/2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/021977Orig1s037.pdf. Accessed July 20, 2015.

[10] Bray GA. Medical treatment of obesity: The past, the present and the future. Best Pract Res Clin Gastroenterol. 2014;28(4):665-84.

[11] Rasmussen N. America’s first amphetamine epidemic 1929-1971: A quantitative and qualitative retrospective with implications for the present. Am J Public Health. 2008;98(6):974-985.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377281/. Accessed June 3, 2015.

[12] Food and Drug Administration. Label: Lisdexamfetamine dimesylate (VYVANSE). 11/2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021977s033lbl.pdf. Accessed June 3, 2015.

[13] Food and Drug Administration. Medical review: Lisdexamfetamine dimesylate (Vyvanse). NDA#: 21-977/S037. Approval Date: 1/30/2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/021977Orig1s037.pdf. Accessed July 20, 2015.

[14] National Library of Medicine. Belviq – lorcaserin hydrochloride hemihydrate tablet. DailyMed. Updated December 2014. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cbbb12f- 760d-487d-b789-ae2d52a3e01f. Accessed June 3, 2015.

[15] National Library of Medicine. Qsymia – phentermine hydrochloride and topiramate capsule, extended release. DailyMed. Updated September 2014. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40dd5602-53da-45ac-bb4b- 15789aba40f9. Accessed June 3, 2015.

[16] DailyMed. Drug Label: Vyvanse – lisdexamfetamine dimesylate capsule. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=704e4378-ca83-445c-8b45- 3cfa51c1ecad. Accessed June 23, 2015.

[17] Food and Drug Administration. Medical review: Lisdexamfetamine dimesylate (Vyvanse). NDA#: 21-977/S037. Approval date: 1/30/2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/021977Orig1s037.pdf. Accessed July 20, 2015.

[18] Ibid.

[19] Ibid.

[20] Ibid.

[21] Ibid.

[22] Ibid.

[23] Ibid.

[24] Ibid.

[25] Ibid.

[26] Ibid.

[27] Ibid.

[28] Brownley KA, Peat CM, La Via M, Bulik CM. Pharmacological approaches to the management of binge eating disorder. Drugs. 2015;75:9-32.

[29] Diet and exercise: Still the best medicine for losing weight or keeping fit. Worst Pills, Best Pills News. October 2012. /newsletters/view/817. Accessed June 3, 2015.