Will Ambien Go the Way of Halcion?

In the early 1990s, word was spreading that Halcion, a popular short-acting sleeping pill prescribed for insomnia, was a dangerous drug. Not only did it make users anxious, depressed, and suicidal.

It was also implicated in a series of murders. Sales of Halcion plunged. Today the drug is still on the market but is rarely prescribed.

Now zolpidem (Ambien) is receiving intensive post-marketing scrutiny, raising questions about the drug’s safety.

Ambien now is known to cause adverse effects and its use may decreaseIn the early 1990s, word was spreading that Halcion, a popular short-acting sleeping pill prescribed for the treatment of insomnia, was a dangerous drug. Not only did it make users anxious, depressed, and suicidal.

It was also implicated in a series of murders. (The murderers were absolved of their crimes based on the argument that Halcion rendered people incapable of understanding their actions). Sales of Halcion plunged. Today the drug is still on the market but is rarely prescribed.

Now zolpidem (Ambien) is receiving intensive post-marketing scrutiny, raising questions about the drug’s safety. In January 2013 the Food and Drug Administration lowered the recommended dose for women and older adults from 10 mg to 5 mg following reports of zolpidem-related car crashes and an analysis linking the drug to drowsiness in the morning. Studies and reports published in the past 2 years cast more doubt on the drug’s safety. So is zolpidem now set to go the way of Halcion?

A Popular Sleeping Pill

About 5 million Americans now use medications containing zolpidem (generic zolpidem, Ambien, Ambien CR, Intermezzo, Edluar, and Zolpimist), according to the Institute for Safe Medication Practices. Like several other sleeping pills, zolpidem acts on GABA-producing neurons, helping tranquilize the brain.

Benzodiazepine drugs like Halcion bind to several kinds of GABA receptor complexes and consequently produce a range of adverse effects. Zolpidem binds more selectively. Early tests showed that it facilitated sleep and produced fewer adverse effects.

So the FDA in 1992 approved zolpidem for “short-term treatment of insomnia characterized by difficulties with sleep initiation.” FDA approval of the extended-release version came in October 2005—notably without the short-term restriction. Zolpidem in its many formulations dominated the hypnotics market for years despite occasional reports of people sleepwalking, sleep eating, and sleep driving under its influence.

A Troubling CDC Report

People with zolpidem-related problems and injuries were also showing up in hospital emergency departments. The Centers for Disease Control and Prevention recently reported on a survey of psychiatric medications identified as the reason for emergency department visits.

The results were surprising: of all psychiatric medications prescribed, zolpidem ranked first in adverse drug event cases. About 11.5 percent of all emergency department visits among adults were attributable to zolpidem, as were 21 percent of the visits in adults 65 and older. Authors of the report estimated that zolpidem accounted for 10,212 annual visits to hospital emergency departments, 25 percent of which required hospital admission.

Regular Users at Risk

Two new cohort studies suggest that it’s the regular users of zolpidem who are prone to serious accidents:

  1. In a study in Mayo Clinic Proceedings (May 2014), Taiwanese investigators found that long-term zolpidem use significantly increased the risk of major injuries requiring hospitalization. Depending on the dosage, users young and old were 2 to nearly 5 times as susceptible as nonusers to head injuries and fractures.
  2. In a large study in the American Journal of Public Health (August 2015), University of Washington researchers used new prescription and collision records to determine the relationship between the use of sleeping pills and motor vehicle crashes. Regular users of zolpidem were over twice as likely to have crashes as nonusers.

Some Perspective on the Problem

Why is a medication approved as safe and effective by the FDA causing so many problems? The Institute for Safe Medication Practices analyzed a 2012 health care survey to find out if zolpidem was being prescribed and used in a manner consistent with safe use guidelines. Here’s a summary of the report, which appeared in the May 6, 2015, issue of QuarterWatch:

  • Zolpidem was originally approved for short-term use only, yet 68 percent of the users with drug-related injuries or problems were long-term users of zolpidem, on average taking a pill about 2 nights out of 3.
  • Despite the FDA’s recent recommendation that women and older adults be prescribed the lowest approved dose of the drug (5 mg zolpidem or 6.25 mg extended release), in 2012 (before the recommendation came out), few people were taking the lower dose.
  • Drug-drug interactions were common among regular users of zolpidem. Prescribing information warns against taking other drugs that depress the central nervous system while taking zolpidem. Yet about 22 percent of regular zolpidem users were also using opioids on a sustained-use basis. About 23 percent were taking another drug (a benzodiazepine, pregabalin, or gabapentin) that, like zolpidem, acts on the GABA system, producing complex effects.
  • Finally, the prescribing information for zolpidem says the drug may worsen depression and suicidal thoughts in patients with depression. Yet 34 percent of the regular users of zolpidem were also using an antidepressant.

Many regular users of zolpidem may never experience drug-related complications. (This may also have been the case for the majority of Halcion users.) But with so much data now showing that zolpidem is causing harm to significant numbers of users, prescribing patterns will likely change. Don’t be surprised if the next time you ask for a renewal of your zolpidem prescription, you’re prescribed something else instead.

If you use zolpidem for insomnia, how do you feel about the possibility of losing access to this sleeping pill?

Sleep Eating: It Finally Happened to Me

Parasomnias like sleepwalking, sleep driving, sleep eating, and sleep texting make me wonder: what would it be like to wake up in my car “high-centered on a rock,” as an acquaintance said he did, or to kitchen cabinets covered with the glutinous remains of barley soup?

What happened to me a few nights ago is the strangest sleep-related experience I’ve ever had.

fridgeParasomnias like sleepwalking, sleep driving, sleep eating, and sleep texting make me wonder: what would it be like to wake up in my car “high-centered on a rock,” as an acquaintance said he did, or to kitchen cabinets covered with the glutinous remains of barley soup?

What happened to me a few nights ago is the strangest sleep-related experience I’ve ever had. No, it had nothing to do with alcohol or Ambien (which can cause parasomniac behaviors like sleep eating)–that night I hadn’t touched either one. But I was feeling super stressed out and short on sleep.

A Rude Awakening

In the middle of the night I awakened feeling there was something in my mouth. I swallowed reflexively and then regretted it: whatever was in there definitely was not fit to eat. It felt like tiny bits of plastic mixed with sand and Kleenex. It tasted vile.

What on earth had I done? Taken a mouthful of garbage? Slept with my mouth open and some shiny-shelled insect crawled inside? Yuck and double yuck!

I rushed to the bathroom and spat into the sink. Then I rinsed my mouth with water several times, but the awful taste remained. Could what I’d swallowed be harmful? Exactly what would be the consequences of this disgusting midnight snack? I gargled with mouthwash and then returned to bed.

The curious thing is that I actually fell back to sleep. On any other night, my brush with sleep eating would have sent my body’s early warning system through the roof. Danger, danger! my hormones would have screamed. No way could I have returned to sleep thinking about the poison that just went down the hatch. But on this particular night, my need to sleep trumped even that.

Everything Is Illuminated

I saw exactly what had happened in the morning. The bottle of Omeprazole (a.k.a. Prilosec) capsules I keep on my bedside table was empty, the contents strewn all over my bed and on the floor. The capsule I normally take first thing in the morning for help with digestion had become an after-hours dining experiment instead. But rather than swallow it whole, I held it (or them) in my mouth like a cough drop—to revolting effect.

I must admit the experience shook me up. If I can take pills in my sleep, what’s next? Swallowing a refrigerator magnet? Throwing compost on the neighbors’ lawn?

Becoming a member of the Parasomnia Society does give pause.

What’s the strangest thing you’ve ever done in your sleep?