The Big Sleep: Do Sleeping Pills Cause Premature Death and Cancer?

Adults who use sleeping pills are more than three times more likely to die prematurely compared to matched controls who don’t use sleeping pills, according to a recent study. (1)

I’ve never been a fan of sleeping pills, even the newer, first-line “Z” medications: zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). I’ve seen all of them cause more harm than good in my patients, but that’s not surprising, since I treat patients with addictions.

These newer sleeping medications are touted by many as being safer and less addictive than older medication like temazepam (Restoril), triazolam (Halcion) or clonazepam (Klonipin). However, all of the “Z” medications are Schedule IV controlled substances, just like their benzodiazepine predecessors. This means they all have roughly the same potential to cause addiction, despite some enthusiastic and misleading marketing done by some drug companies.

But I know many people, without a history of addiction, can take sleeping pills without apparent problems, so I was surprised to read about this recent study. This relatively large study looked at the medical records of over 10,000 patients who were prescribed hypnotics for sleep, and compared their outcomes to over 23,000 matched control patients, similar except the controls weren’t taking sleeping pills.

The sleeping pills, also called “hypnotics” were associated with significant increases in mortality and  significant increases in cancer incidence.

The patients’ average age was 54, and they were followed for an average of 2.5 years. All were members of a large U.S. healthcare system in Pennsylvania. The data from the two groups were adjusted for age, gender, smoking status, prior cancer diagnoses, body mass index, ethnicity, and alcohol use.

Patients in the group taking prescribed hypnotics most frequently, defined as more than 132 doses per year, had  over five times increased risk of dying than patients not taking hypnotics. Even the group of patients taking hypnotics relatively infrequently (up to 18 doses per year) had a three times higher risk of death. These differences were statistically significant. The medications in the study included all of the “Z” medications, as well as temazepam (Restoril), barbiturates, and the sedating antihistamines, such as diphenhydramine (Benadryl).

Of note, eszopiclone (Lunesta) was associated with the highest risk of death. (This pill’s advertisement has a beautiful butterfly wafting in through an open window, and landing gently by a woman in bed, presumably  helping her sleep. I guess the butterfly seemed like a better commercial symbol that the grim reaper.)

The use of hypnotic medications was also associated with an increased risk of cancer, and reached statistical significance in patients taking the most hypnotics. Lung, colon, and prostate cancers were significantly more likely to occur in these hypnotic medication users, as well as lymphoma.

The author estimated that hypnotic medications are associated with 320,000 to 507,000 deaths in the U.S. over the year 2010.

This study raises some important questions, since hypnotic drugs are the most commonly prescribed drugs in the U.S., with an estimated 6 to 10% of the population being prescribed these medications.

This study really intrigued me. It’s the first I’ve read or heard about this association between sleeping pills and death, other than overdoses from mixing such drugs with opioids. After reading this article, my first thought was, “I wonder if more studies will show the same thing.” Then I started looking on the internet and found other studies that show an association between sleeping pills and increased risk of death. Many of these studies had flaws, but the overall impression is that this is a real correlation. The author of this current large study, Dr. Kripke, goes so far as to say the risks of hypnotic medications outweigh their benefits. He also admits his bias against hypnotics. (2)

Sleep medicine doctors say that correlation doesn’t mean causation, and we shouldn’t jump to conclusions. One sleep specialist pointed out that the study didn’t control for psychiatric illness, which could be a significant factor. Additionally, patients who are prescribed sleeping medications may be sicker overall, in ways the study didn’t control, and therefore a generally less healthy group. This could distort study findings.

Other scientists say that sleeping pills could make sleep apnea worse, and cause deaths in that way. Obesity increases the risk of sleep apnea, and with more adults becoming obese, perhaps sleeping pills make apnea worse and these people die in their sleep. Other scientists say sleeping pills slow reflexes, and perhaps patients taking these medications are more likely to be involved in car accidents and other accidents, increasing their death rates.

As for my patients, many of whom are prescribed methadone or buprenorphine, the risk of drug interaction and overdose with the hypnotics usually outweighs all of the benefits, and I recommend that patients do not mix these two types of medications.

So stay tuned. As time goes on, hopefully we’ll learn more about this correlation between sleeping pills and death. This current study is helpful because of its large size, and the author points out that 19 other studies have shown a relationship between hypnotics and increased risk for death.

Let’s also consider that sleeping medications bring in more than a billion dollars a year to the drug companies that sell them. I’ll be looking for more studies that are not funded by drug companies.

  1. BMJ Open2012;2:e000850 doi:10.1136/bmjopen-2012-000850



5 responses to this post.

  1. Posted by dbc1823417993312314 on April 11, 2012 at 1:59 pm

    WOW! I wish I could say I was surprised by this, but the *obvious* problem is that profits are the #1 concern of the pharmaceutical industry. Therefore, they often rush through clinical trials, make over-hyped claims, then discover later some harm caused by medication X. The subsequent class action lawsuit is usually just a speeding ticket for them. If only one of their 100 high priced medications get ‘busted’, then ‘Oh well’.

    The even more disturbing thing, to me, is how ineffective a lot of medications are these days. Take modern anti-depressants. In double-blind placebo clinical trials, they were *barely* more effective than sugar pills, yet they are constantly given to those with ‘depression’ right off the bat, despite the side effects the may cause, and *despite* the FACT that it takes real psychological counseling and/or work to overcome to cause of the depression.

    Of course, I do have the ‘opposite’ view of most doctors. I believe that *minor* (non drug dependent) neurochemical imbalances are not the *cause* of depression, they are more likely a symptom of it — that’s how the body manifests depression. The fact that many of these modern drugs take weeks to even start working, and have very subjective testing criteria makes them even more dubious (e.g. how do you measure real change in clinical degree depression in an accurate way? It is very difficult and is up to patients answers).

    Then there is the issue of ‘professional guinea pigs’ who sign up for every drug trial they can. These hardly are good test candidates, but nobody cares.

    This is what happens when money is injected into healthcare.


    • The problems with our healthcare system are legion.

      Antidepressants do work – it’s just that many patients aren’t willing to take them for long enough. It really takes a couple of months for many of them. But in the right patient, anti-depressants can be life-changing in a very good way.


  2. Posted by Jason on April 11, 2012 at 4:23 pm

    Dr. J: Everything I’ve read regarding taking benzodiazepines and Suboxone together say it’s ok to take if you are already tolerant to Suboxone. I know you’re talking about the newer hypnotics, but just curious to see your thoguhts on benzos and bup.


    • Well, it depends on why the person is taking Suboxone. Presumably, it’s because of an opioid addiction. We know that people with addiction to one substance commonly develop addiction to another. I’m not talking about physical dependence – I’m talking about obsession and compulsion to take the substance despite adverse experiences. Because of this, I think benzos are a very high risk drug – not only can they still cause overdose deaths with Suboxone, tolerant or not, but the person risks a whole other addiction.
      And we need to weigh the benefits of benzos, too. They can be very effective in the short-term, for less than 3 months, when treating an anxiety disorder. But there’s no indication for long-term use in anxiety disorders, and in fact there are studies that show anxiety worsens on benzos. Tolerance develops quickly to the anti-anxiety effect of benzos.
      I think in most cases, better medication can be found to treat the anxiety. According to published guidelines, the only indications for long term benzos are anxiety in terminal illness, and rare neurologic conditions, such as “stiff man syndrome.”
      Benzos are second or third line treatents for other illnesses. And let’s not forget that cognitive-behavioral therapy shows the best long-term outcomes for patients with some of the anxiety disorders.


  3. Reblogged this on MI Hygienist NZ – Speaking for Myself and Oral Health and commented:
    Interesting appraisal and reflection of your concerns for your patients. It is good to see the balance in your text.


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