Dreams or Dementia? The Dangers of Z-Drugs to Get ZZZs

People who have trouble sleeping are caught in a tough double bind. On the one hand they are told that sleep is essential for good health. Without it, people are prone to obesity, hypertension, diabetes, depression and cognitive difficulties. On the other hand, if they decide to use sleeping pills long term, there are risks to consider. Some of the most popular drugs for insomnia are the so-called Z-drugs such as zaleplon (Sonata),  zolpidem (Ambien) and eszopiclone (Lunesta).

From Bromides to Benzos: The Shifting Science of Sleep:

Humans have struggled with sleep for millenia. For much of that time they needed to be on guard against attack from  animals or adversaries. These days, people worry about finances, family matters, politics, climate catastrophes or just the overwhelming onslaught of modern life. Such concerns can make sleep a struggle.

Before there were Z-Drugs there were lots of sedating sleeping meds:

Here is an ultra-short history of the quest for a decent night’s sleep:

Laudanum:

When people complained about insomnia in England during the 18th century, doctors would likely have prescribed laudanum. This bitter red tincture contained 10% powdered opium in alcohol. And yes, it would have helped people sleep, but it was also addictive.

Chloral Hydrate:

Another early sleep aid was developed in the late 19th century. A German chemist created a sedating compound called chloral hydrate. It came as a powder or syrup and doctors prescribed it for anxiety and/or insomnia. Unscrupulous bartenders would sometimes add chloral hydrate to drinks to create “knock out drops.”

This combo became known as a “Mickey Finn” or a “Mickey.” Unconscious patrons could be robbed. There is also a story that bartenders would add a sedative like chloral hydrate to drinks. Sea captains who were desperate for crew members would presumably pay for these unconscious patrons. They were “shanghaied” for long ocean voyages.

Bromides:

Potassium bromide was also employed as a sedative in the 19th century. It was a bit more effective as an anticonvulsant than as a sleeping pill and fell out of favor fairly quickly.

Barbiturates:

In the early 20^th century, barbiturate sleeping pills became hugely popular. Amobarbital (Amytal), pentobarbital (Nembutal), phenobarbital (Luminal) and secobarbital (Seconal) were prescribed for anxiety and/or insomnia. The trouble with such drugs was that overdoses were lethal. Combining a barbiturate with booze was even more deadly. Marilyn Monroe and Judy Garland were among the victims of barbiturate overdose.

Benzodiazepines:

When benzodiazepines appeared in the early 1960s they also became incredibly popular. Starting with chlordiazepoxide (Librium) and diazepam (Valium), these drugs were hailed as safer sleeping pills and sedatives. Overdoses were far less likely to lead to death. By 1966, such medicines were immortalized by the Rolling Stones in their song “Mother’s Little Helper.”

To this day, drugs such as alprazolam (Xanax), clonazepam (Klonopin) and lorazepam (Ativan) are prescribed in large numbers to treat anxiety and insomnia.

The Evolution of Z-Drugs:

Because sedatives and sleeping pills developed a somewhat shady reputation, drug companies and doctors started calling newer drugs “hypnotics.” It seemed as if that term was somehow less worrisome. If a doctor told a patient that he was prescribing a hypnotic called zolpidem for insomnia it may have seemed safer than a benzo.

Each time a new kind of “hypnotic” was introduced to aid in the quest for a good night’s sleep, there was positive spin. The downside of everything from laudanum to benzodiazepines was discontinuation. Once patients became dependent upon such drugs it could be very hard to stop taking them. The body adapts and rebels when the drugs are suddenly discontinued. Withdrawal symptoms of benzos include anxiety and agitation, irritability, impaired concentration, panic, insomnia, depression, muscle twitching, sweating and seizures.

When the Z-drugs were introduced, they seemed like a big advance for insomniacs. Drugs such as zolpidem (Ambien), zaleplon (Sonata) and eszopiclone (Lunesta) were perceived as more effective and less likely to cause dependence than benzodiazepines.

Benzos and Cognitive Impairment:

Evidence has been mounting that both benzos and Z-drugs have unexpected side effects, especially in older people. A long-term French study published in 2012 showed a 50 percent increase in the risk of dementia among people over 65 who used a benzodiazepine to help with sleep (BMJ, Sept. 27, 2012). There was, not surprisingly, push back. Others responded that there might be “an association between benzodiazepine use and the subsequent diagnosis of dementia but it does not show causality (BMJ, Nov. 26, 2012).

A follow-up study in the BMJ (Sept. 9, 2014) concluded that:

“Our study reinforces the suspicion of an increased risk of Alzheimer type dementia among benzodiazepine users, particularly long term users, and provides arguments for carefully evaluating the indications for use of this drug class.”

Since then the battle has raged up and down. A study in the Journal of Personalized Medicine (Oct. 12, 2024) included five meta-analyses encompassing 30 studies. It concluded:

“This study examined the associations between benzodiazepine use and the risk of dementia. Although all meta-analyses found significant relationships between benzodiazepine use and dementia risk, the strength of the evidence was weak due to the low methodological quality of the included studies.”

To confuse things even more, the most recent meta-analysis of benzodiazepine (BZ) use in older adults published in the Harvard Review of Psychiatry (Jan-Feb, 2025) concludes:

“Our findings did not reach statistical significance, suggesting no strong link between chronic BZ use and dementia.”

What About Z-Drugs and the Brain?

A reader recently asked:

Q. I jump into bed every night and before you can say Vladivostok, I’m sleeping like a redwood log. However, it’s a safe bet that I’ll be wide awake around 2 or 3 AM counting the popcorn on my ceiling for the rest of the night.

My doctor prescribed Ambien, and it was great. I got my first good night’s sleep in years.

Incredibly, he advised me to take it only when needed. Since I had been waking up every single night to start with, where does that leave me? I cut the 10 mg tabs in half to make them last longer and found that 5 mg still worked pretty well.

Are there any sleep aids out there without warnings about continued use? What good is a temporary solution to an ongoing problem?

A. The history of sleeping pills is a tale of woe and intrigue. Decades ago, doctors prescribed barbiturates such as secobarbital (Seconal) or pentobarbital (Nembutal). They knocked people out, but the risk of overdose and dependency was high. Then came benzodiazepines such as chlordiazepoxide (Librium) and diazepam (Valium). There were similar concerns with such drugs.

When the FDA approved zolpidem (Ambien) in 1992, it was promoted as a safer alternative. However, the official prescribing information currently states that the drug is intended:

“for the short-term treatment of insomnia…”

including for people who wake in the middle of the night.

A recent study in the journal Cell (Jan. 8, 2025) suggests that zolpidem may interfere with an essential function of sleep: clearing the brain of waste products. This might increase the risk for neurologic disorders later in life.

A systematic review published in Translational Research & Clinical Interventions (Jan. 21, 2025) notes that a number of studies have observed an association between hypnotics and dementia. But as with the benzos, there is significant variability in findings with regard to Z-drugs and dementia. A review in the Frontiers of Human Neuroscience, Dec. 9, 2021 concluded:

“We found that BZD [benzodiazepine] exposure density was an independent risk factor of cognitive impairment in middle-aged and older patients with chronic insomnia, but no correlation was found between Z drug use and cognitive impairment. Moreover, our study showed that Z drug use might protect attention compared with non-Z drug use. Additionally, income level, the severity of insomnia, and age were also independent factors of global cognitive function. Our findings suggested that the cognitive status should be extensively evaluated and monitored in middle-aged and older patients with sedative-hypnotics; the prescription of BZDs should be avoided or limited in low doses. Although there is no evidence of cognitive decline in this study, the occurrence of side effects and death of Z drug may be similar to that of BZDs. Z drugs should also be prescribed with great caution in middle-aged and elderly.”

One Other Risk with Z-Drugs:

We worry about the increased likelihood of a fall among older users of any sleep medications, including the Z-drugs. Falls among older people can result in life-threatening fractures.

Researchers from the CDC and Johns Hopkins School of Public Health found that such “psychiatric medications” were implicated in many emergency department visits (JAMA Psychiatry, July 9, 2014). Zolpidem stood out as the drug behind 20 percent of ER visits among older adults.

There is also the risk of driving impairment. The connection between Z-drugs such as zolpidem and automobile accidents is worrisome. You can read our article on this problem at this link.

Morning-after “hangover” can affect anyone. That’s why the FDA reduced the dose of zolpidem for women from 10 mg to 5 mg. It’s difficult for drivers to evaluate impairment caused by such medications.

What’s the Benefit/Risk Ratio with Z-drugs?

How much benefit do people get from sleeping pills? That’s a bit harder to parse. Dartmouth doctors Schwartz and Woloshin have pointed out that there is some uncertainty associated with Z-drugs such as (Lunesta) eszopiclone (New England Journal of Medicine, Oct. 29, 2009):

“In the longest, largest phase 3 trial, patients in the Lunesta group reported falling asleep an average of 15 minutes faster and sleeping an average of 37 minutes longer than those in the placebo group.”

For some people, an extra 37 minutes might be enough to make a difference. For others, not so much. Each person will have to determine if the benefits are strong enough to warrant long-term treatment with a hypnotic drug.

There are some other options, though. Cognitive behavioral therapy can be effective against insomnia. Vigorous exercise during the day, a high-carb snack in the evening or a hot bath an hour before bed may help people fall asleep more quickly. There is also self-hypnosis to create a sense of relaxation.

For more information on sleeping pill pros and cons and non-drug approaches to overcoming insomnia you may our eGuide to Getting a Good Night’s Sleep helpful. They include tart cherries, magnesium, valerian, lemon balm, lavender, ashwagandha and hops. This online resource is available under the Health eGuides tab.