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John Cruz
Faculty peer reviewed
A number of studies have shown that zolpidem (Ambien), the most commonly prescribed sleep-inducing medication on the market, can produce uncontrollable nocturnal eating behavior among users. Sleep related eating disorder (SRED) is characterized by partial arousals from sleep to ingest food, usually within the first three hours after sleep onset, occurring one to six times per night.1 Patients describe an “automatic” inclination to eat and an inability to return to sleep unless they eat. The foods are often high in calories and ingested in massive quantities.2
The occurrence of zolpidem-induced nocturnal eating is probably more common than currently reported. In a New York Times article3 entitled “Study links Ambien use to unconscious food forays,” Stephanie Saul interviewed Judie Evans, a 59-year-old woman who lived alone and suffered from zolpidem-induced SRED. At the time of her diagnosis, Ms. Evans was recuperating from spinal surgery, wore a full body cast, and always required help to get out of bed. Shortly after her physician prescribed zolpidem for her sleeping difficulties, she noticed that food started to disappear from her home. She initially accused the two nursing aides who were caring for her, but it was not until her son stayed with her for several days that she realized what was really occurring. “During the day, I couldn’t even make it to the bathroom by myself,” Ms. Evans said. However, on the first night he stayed over, her son found her, body cast and all, frying eggs and bacon in the kitchen. The next night, he caught her eating a sandwich and promptly sent her back to bed, but later found her back in the kitchen with the oven turned to 500 degrees, causing the pots stored in the oven to melt.3
Another woman who suffered from SRED was Helen Cary, a labor and delivery nurse in Dickson, Tennessee. Ms. Cary started taking zolpidem to help her sleep through the day so that she could work 12-hour night shifts at the hospital. Although she said that zolpidem helped her survive “five years of night shift,” she felt “very ambivalent” about the medication because while on zolpidem her behavior became very strange. “One day,” she said, “I got up-my husband describes this in great detail-I got a package of hamburger buns and I just tore it open like a grizzly bear and just stood there and ate the whole package. He said a couple things to me until he realized I was asleep.” Ms. Cary no longer takes zolpidem, and has switched to working days.3
Zolpidem is a benzodiazepine agonist that binds to the benzo 1 receptors found in the cortex and cerebellum and creates a hypnotic effect. However, unlike the anxiolytic drugs alprazolam (Xanax) and clonazepam (Klonopin), zolpidem does not bind to the benzo 2 receptors in the striatum, hippocampus, and spinal cord, and is less likely to cause ataxia, dependence, paradoxical disinhibition, withdrawal symptoms and, most importantly, respiratory depression.4 Consequently, many doctors prescribe zolpidem to treat insomnia.
A number of sleep experiments have confirmed the relationship between zolpidem and nocturnal eating. Dr. Michael Silber was one of the first to describe SRED with amnesia in zolpidem users. In a 2002 article,5 he described three cases where nocturnal eating began as a result of starting zolpidem and two cases where pre-existing nocturnal eating increased in frequency.
Melissa Feltmann, a spokesperson for Sanofi-Aventis, the French company that makes zolpidem, defends the safety of the drug. She states that “Sanofi-Aventis has received reports of people eating while sleepwalking and those reports, like all reports of adverse events, have been provided to the U.S. Food and Drug Administration.” Ms. Feltmann says that the package insert for zolpidem warns that the drug may cause a sleep-related eating disorder, but she cautions that every case of SRED in patients taking zolpidem might not necessarily be caused by the drug itself.3
A definitive etiology has not been elucidated, but a number of hypotheses are currently being explored. Dr. Carlos Schenck, a sleep disorders expert at the University of Minneapolis, believes that under the influence of zolpidem, sleeping and eating become confused by the brain.3 Morgenthaler5 and Mahowald6 further elucidate Schenck’s hypothesis. They found that the concurrence of a sleep disorder that increases arousals during slow-wave sleep (e.g. restless leg syndrome; periodic limb movement disorder; obstructive sleep apnea; and withdrawal from nicotine, alcohol, opiates and cocaine) can often lead to SRED in the setting of zolpidem use.
Until researchers discover the exact mechanism by which zolpidem causes SRED, treatment options include targeting the underlying sleep disorder (pramipexole for restless leg syndrome, CPAP for sleep apnea), discontinuing zolpidem, and replacing zolpidem with another benzodiazepine agonist such as eszopiclone (Lunesta) or pyrazolopyrimidine (Sonata).5 Najjar et al. found that despite being in the same medication class as zolpidem, eszopiclone and pyrazolopyrimidine were associated with resolution of SRED.7
Until further studies elucidate the exact mechanisms by which zolpidem induces SRED, physicians should exercise caution when prescribing it, especially in obese or diabetic patients.
John Cruz is a fourth year medical student at NYU Medical Center.
Peer reviewed by Andrea Kondracke MD
References
1) Winkelman JW. Clinical and polysomnographic features of sleep-related eating disorder. J Clin Psychiatry. 1998;59:14-19.
2) Schenck CH, Hurwitz TD, Bundlie SR, Mahowald MW. Sleep-related eating disorders: polysomnographic correlates of a heterogeneous syndrome distinct from daytime eating disorders. Sleep. 1991;14(5):419-431.
3) Saul S. Study links Ambien use to unconscious food forays. NY Times. March 24, 2006. http://www.nytimes.com. Accessed on October 21, 2009.
4) Albers LJ, Hahn RK, Reist C. Handbook of Psychiatric Drugs 2008. Hightown, Lancaster, UK: Current Clinical Strategies:72.
5) Morgenthaler TI, Silber MH. Amnestic sleep-related eating disorder associated with zolpidem. Sleep Med. 2002:3(4)323-327.
6) Mahowald MW, Schenck CH. NREM sleep parasomnias. Neurol Clin. 1996;14(4):675-696.
7) Najjar M. Zolpidem and amnestic sleep related eating disorder. J Clin Sleep Med. 2007;3(6):637-638.
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