Can I just tell you that I am slightly frustrated by the fact that I know A LOT about sleep, and not afraid to say it. I studied it exclusively for a year at Duke as a Fellow (after my 4 years of medical school and after my four years of Neurology residency and Neurology certification) to be "Fellowship Trained" in Sleep Medicine and delaying entering the final medical work force by a year just so I could understand sleep that much better. I lecture on it, write articles on it, get consulted about it from fellow physicians.....
AND then my referring docs and patients just want to slap on some wine before bed, or Ambien before bed, or Lunesta before bed, etc. Or they google-read that Dr. Velpo's Magic Supplement (just made that up) will cure their sleep issues.
In they end, they are just masking the real problems... and I care about the real problem, not the sleep. The sleep issue is just a consequence.
95% or more of humanity needs no help sleeping if you treat the underlying problem. Which means 95% or more of the patients I see on one of the hypnotics could come off if we addressed the problem they are trying (and always failing) to mask with the medication.
Okay, stepping off my soapbox, what are the hypnotics:
They are used to make you sleep, whether it be deep enough to cut out an appendix or deep enough to sleep through your husband's snoring.
The list is too long to type here, but I'll mention some of the common ones I see (by their generic names since the drug pharmacy brand names changes from time-to-time):
-Zaleplon
-Zolpidem
-Zopiclone
-Triazolam
-Midazolam
-Temazepam
-Alprazolam
-Alcohol
-Diphenhydramine
-Melatonin
-Ramelteon
-Mirtazapine
-Trazodone
-Risperdone
-Quetiapine
-Olanzapine
-Marijuana
There are MANY reasons to come of these medications if used just for sleep, such as changes in the quality of your sleep with long-term use, change in the sleep stages you get with long-term use, next-day affects on thinking and mood because they change the way your brain tries to rest itself while you sleep, interaction with other medications (usually subtle and under appreciated), unnecessary extra costs, masking the real underlying problem which may be very unhealthy or even deadly if left untreated.... etc.
This study just added to that concern. You can read below the line for more details.
But in summary, they sifted through 10,531 patients from a large U.S. health system who WERE taking a hypnotic (presciption: alcohol, marijuana, etc didn't count) to help them sleep and compared them to 23,674 patients who were NOT taking a hypnotic between the years of 2002 and 2006 to help them sleep. They followed them for 2 and a half years.
Of the people taking sleep agents, 6.1% died.
Of the group not taking anything, 1.2% died.
The more pills one took, the higher their chance of dying.
They even stratified it to amount of use:
HR 3.60 for 0.4 to <18 pills
HR 4.43 for 18 to 132 pills
HR 5.32 for >132 pills
What the above says is that if you take 18 pills a year to help you sleep.... you are 3.6 times more likely to die than if you didn't need the medication.
If you need it more than 18 times but less than 132 times a year, you are 4.43 times more likely to die than if you didn't need the medication.
If you need a sleeping pill more than 132 times a year, you are 5.32 times more likely to die than if you didn't need the medication.
Now, they didn't tell why all these people died, or if the medication was responsible directly (unable to prove) nor how it might be indirectly responsible. This was just a study to note the trend. I think the trend is more trustworthy given the huge numbers of patients involved in the study. The more people in the study, the more the "odd" or "unique" cases become less relevant and even out in the wash.
Take home message: Stop masking the problem. Let's get it straightened out.
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The use of hypnotic sleep aids was associated with a three- to five-fold higher mortality risk compared with the risk for nonusers, even when the prescription was for a small number of pills, investigators reported.
A prescription for 0.4 to 18 doses per year was associated with a mortality hazard ratio of 3.60 compared with patients who had no prescriptions for hypnotics.
The hazard jumped to 5.32 for patients prescribed more than 132 doses a year, investigators reported online in BMJ Open.
"Rough order-of-magnitude estimates ... suggest that in 2010, hypnotics may have been associated with 320,000 to 507,000 excess deaths in the U.S. alone," Daniel F. Kripke, MD, of the Scripps Clinic in La Jolla, Calif., and co-authors wrote. "From this nonrandomized study, we cannot be certain what portion of the mortality associated with hypnotics may have been attributable to these drugs, but the consistency of our estimates across a spectrum of health and disease suggests that the mortality effect of hypnotics was substantial."
Patients who used hypnotics most often also had an increased risk of cancer, with an overall cancer increase of 35% among those prescribed high doses.
More than 30 years ago, investigators in an American Cancer Society-supported study showed that both cigarette smoking and hypnotic use were associated with excess mortality (Arch Gen Psychiatry 1979; 36: 103-116). But the link to hypnotics was largely discounted because the study was not designed primarily to examine these drugs, Kripke and colleagues wrote.
Subsequently, at least two dozen studies examined the mortality risk associated with hypnotic use, and two-thirds of the studies demonstrated significant (P<0.05) associations. Lack of uniformity across the studies precluded a meta-analysis, but 22 of the reports showed a mortality hazard ratio that exceeded 1.0, the authors continued.
Previous studies had several notable limitations, including limited information on the specific types of drugs, confounding with tranquilizers, lack of monitoring of the quantities of drugs provided to patients, and limited data on newer short-acting hypnotics, such as zolpidem, zaleplon, and eszopiclone (Lunesta).
To address some of the limitations of previous work, Kripke and colleagues performed a matched-cohort study based on longitudinal data from a large U.S. health system.
A query of the database identified 10,531 adult patients who had at least one prescription for a hypnotic drug from Jan. 1, 2002 to Sept. 30, 2006. Using the same database, the authors matched the hypnotic-user group with 23,674 patients who did not have a prescription for a hypnotic during the period studied.
Three-fourths of patients prescribed a hypnotic had an explicitly stated sleep-related indication in their records.
Women (mean age 54) accounted for 63.9% of hypnotic users. Hypnotic users and the control group had been followed for about 2.5 years. The users had a mean morbidity score of 1.53. Zolpidem was the most commonly used hypnotic (4,338), followed by temazepam (2,076).
Overall, 6.1% of hypnotic users died during observation, compared with 1.2% of the nonusers. Hypnotic use was associated with a significantly increased mortality risk (P<0.001). The magnitude of the hazard ratio increased with the number of pills prescribed per year (P<0.001 for all comparisons versus nonusers):
HR 3.60 for 0.4 to <18 pills
HR 4.43 for 18 to 132 pills
HR 5.32 for >132 pills
Separate analyses of the two most commonly used hypnotics showed a similar increase in the mortality hazard. For zolpidem the hazard increased from 3.93 for patients who took 5 mg/year to 130 mg/year, to 5.69 for patients who had prescriptions for >800 mg/year (P<0.001).
Patients with temazepam prescriptions totaling 1 mg/year to 240 mg/year had a mortality hazard of 3.71, increasing to 6.56 for >1,640 mg/year (P<0.001).
Overall, only patients whose hypnotic use fell into the top two categories (18 to 132 pills and >132 pills) had an increased cancer risk (HR 1.20, P=0.022; HR 1.35, P<0.001).
For individual drugs, only patients in the top category of zolpidem use had an increased cancer risk (HR 1.28, P=0.023), whereas the two top categories of temazepam use were associated with an increased mortality hazard (HR 1.44, P=0.024; HR 1.99, P<0.001).
The authors acknowledged limitations to this research, most notably that residual confounding could not be fully excluded "due to possible biases affecting which patients were prescribed hypnotics and due to possible imbalances in surveillance."
They also pointed out that cohort studies may demonstrate an association but do not necessarily imply causality. However, "the preferable randomized controlled trial method for assessing hypnotic risks may be impractical due to ethical and funding limitations," they said.
"The meager benefits of hypnotics, as critically reviewed by groups without financial interest, would not justify substantial risks," the authors wrote. "A consensus is developing that cognitive behavioral therapy of chronic insomnia may be more successful than hypnotics.
"Against meager benefits, it is prudent to weigh the evidence of mortality risks from the current study and 24 previous reports, in order to reconsider whether even short-term use of hypnotics, as given qualified approval in National Institute for Clinical Excellence guidance, is sufficiently safe," they added.
