The Fear of Sleeping Pills Part II: Melatonin, Heart Failure, and the Subtle Art of Not Panicking
OR: “Much Ado About Nothing?”
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By David E. McCarty, MD, FAASM (but you can call me Dave)
17 November 2025
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“O, what men dare do! what men may do! what men daily do, not knowing what they do!”
“Benedick”, in: Much Ado About Nothing [1]
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This just in… (see reference 2)
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The Eight-Year Itch
Every few years, a story barrels through the world of Sleep Medicine with all the grace and subtlety of a runaway parade float—[I speak from experience on the parade float—I lived 15 years in Shreveport, Louisiana, and I’ve seen my share of parade float runaways! LOL!!}—
…but I digress…
The details for this story may be a bit different, but the feeling is the same: it’s an unexpected loudspeaker pressed suddenly against the public ear, blaring some new message of danger…about SLEEPING PILLS.
A couple weeks ago, that loudspeaker announced that long-term melatonin use was “linked” to higher risks of heart failure, hospitalization, and death in adults with chronic insomnia.[2] “Linked” is the kind of word that sounds scientific enough to signal danger while still being vague enough to avoid legal trouble, humming with menace even while the evidence underneath it is softer than the headline implies.
If you felt a little jolt when you saw it, you’re not alone. That was the point.
And we’ve been here before.
But as Shakespeare reminded us in Much Ado About Nothing, we humans tend to act with certainty, long before the truth is fully in view.
In 2017, eight years ago, Dr. Matthew Walker’s runaway train of a bestselling book Why We Sleep [3] lit the fuse on a cultural scare incited by a flawed retrospective chart review about sleeping pills and cancer (Kripke 2012 [4]), launching a thousand panicked phone calls, and accidentally transforming that beautiful book into a bit of a personal frenemy!
I wrote about that moment in 2022 [5] trying to offer something gentler than panic and something clearer than yes-or-no conclusions. My goal then is the same as my goal now: to walk everyone back from the ledge long enough for us to remember how science is supposed to work.
So: deep breaths, Life-Fans!—preferably through the NOSE! LOL! Let’s talk…
I’ll start with this: recently, researchers at the American Heart Association Scientific Sessions meeting in New Orleans announced that long-term melatonin use is associated with a (much) higher risk for Heart Failure hospitalization and death. [2]
Whaaaaa? Let’s take this slowly, together. Surely we can’t be talking about that melatonin…the over-the-counter gummy thing that seems so safe…
Heart failure? Really? From using it for a year?
That’s what the study showed. Looks like a job for EMPOWERMENT…
Walk with me.
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The Cultural Placement of Melatonin
In clinical medicine these days, oral melatonin is widely treated as “harmless” because it is “natural.”
Clinically and experientially, this mostly checks out. Most clinicians will tell you that the side effect profile is pretty benign: there is no signal for habituation, there’s no withdrawal syndrome if chronic usage is suddenly stopped, there is no clinical signal for increased fall risk for those using the drug, and there is no signal that the use of supplemental melatonin suppresses natural melatonin synthesis or release.
In fact, the signal for “lack of harm” is so stable and culturally accepted that melatonin is one of the rare “hypnotics” (a.k.a.: sleeping pills) that is NOT featured on the BEERS CRITERIA list, a living compendium of pharmaceuticals that are considered potentially unsafe for seniors, maintained by the American Geriatric Society. Folks, I’ll put this plainly: melatonin’s the one we choose when the sleeplessness is bad, the patient is suffering, and the patient is perceived to be medically vulnerable.
I hope the kids in the back will recognize what this means, so I’ll state it again: any clinician who intuits patient vulnerability is going to think about safety when they’re reaching for the prescription pen. That means that “sicker-appearing” patients are going to be systematically nudged toward agents with culturally “safer” side-effect profiles, like melatonin. Moreover, the more vulnerable the patient appears, the more likely we are to take their complaint about sleeplessness seriously! Knowing what we know about the importance of getting enough sleep these days, some well-meaning providers might actually insist that the patient take something…something safe…to help with the suffering.
It takes only a little imagination to see how melatonin can get started and never stop.
To me, the folks in the “melatonin” group are starting to seem a little different, even before they put pill one into their mouths.
Welcome to a system that’s biased from the beginning by the problem of self-selection—where the very act of seeking care already divides the population into two fundamentally different groups.
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The Research Question
Nnadi’s team started out with a reasonable question, the kind of question we arguably should ask about any substance that affects our brain and our biology: What happens with long-term use?
Because prospective randomized studies are expensive, the research team did what they could: they looked backwards at medical charts, parsing the data that happened to be there, using big-data analytic tools to crunch the numbers.
The team managed to match melatonin users and non-users across forty covariates, which is no small feat. And, to their credit, they clearly acknowledged that their analysis cannot establish causality. That kind of scientific humility is rare in this kind of research, and they should be commended for it.
The results themselves deserve our attention. Among more than 130,000 adults with chronic insomnia, the group whose records documented at least a year of melatonin use appeared to fare worse—there were higher rates of new-onset heart failure, more hospitalizations and higher mortality--compared to those who did not have a documented exposure to melatonin.
Wow! Interesting. This warrants further study!
But: Life-Fans—this case if far from solved! If this were a court-room drama, Matlock would be pounding on the bench with his fist! This is a dramatic case of circumstantial evidence installed upon a basic landscape of self-selection—all jargon-talk for the statement: the study has built-in flaws and causality has not been demonstrated…
In order to get past the jargon of this, I need to revisit an old parable from my 2022 essay—the story of the Islanders and the FruFru berries…
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The Islanders and the FruFru Berries
Imagine a group of islanders, some of whom adore the taste of a native berry from the FruFru tree. Half the island eats the berries daily; the other half won’t touch them. Researchers swoop in, compare the two groups, and discover that everyone who eats the berries has brown eyes, but NONE of the non-FruFru eaters do! Suddenly the scientists feel the warm, dizzy glow of a Nobel Prize forming. The berries must change eye color! A breakthrough! A revolution!
But then an islander quietly points out that FruFru berries taste like sweet nectar to brown-eyed people and like soap to everyone else. Eye color wasn’t changed by the berries! Eye color selected who wanted to eat them in the first place!
That’s the trouble with self-selection: the groups are different from the beginning…so proving they’re different at the end really shouldn’t come as a huge surprise.
In this melatonin study, the “melatonin group” wasn’t a random sample of the population—it was specifically made up of people…
…who were suffering from insomnia that was bad enough…
… and for long enough…
…that they made a point of going to their doctor about it…
…and they talked about it enough…
…that they achieved the distinction of getting a medical recommendation for “a safe agent” to be used long-term.
If I were to guess at the clinical trajectory of this group, compared to one without such complaints, I’d guess its members would fare worse in all sorts of ways, not just heart failure.
To achieve “documented melatonin” status in this ecosystem, patients had to be suffering (complaining to their doctors) and sufficiently vulnerable to justify recommending the “safe option”.
Get it? “Suffering” means that folks were struggling with the layers of life that insomnia so often wraps itself around: depression, anxiety, trauma, chronic pain, irregular schedules, cardiometabolic instability. “Vulnerable” is an intangible characteristic that made the provider feel compelled to act, and to act with a medication that has been culturally approved as “safer”.
None of these important intangibles was measured or reported—it isn’t even possible.
But all of it is real, captured in the simple detail that these folks came and asked for supervised help, and they got it.
I can’t ignore the fact that the melatonin group started out sicker.
The fact that they ended up sicker shouldn’t come as a surprise to anybody.
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The Problem of Exposure
Another inconvenient problem to note, dear readers: in the United States melatonin is over the counter. Stated differently, in this country, there are millions of people who take melatonin without ever telling their doctor at all. In this case, when we’re considering the notion of causality, that’s not a minor flaw. That’s like putting the sneakiest FruFru berry eaters into the “non-berry” column because nobody happened to write their unmonitored snack preferences in a chart.
Interestingly, this allocation error would be expected to diminish the signal for harm caused by melatonin (assuming melatonin actually was a bad actor). An undocumented exposure in the “non-exposed” group would make the difference in outcomes even harder to detect. In other words, this study is asking melatonin to show us how harmful it is, with one hand tied behind its back…with a diluted and diminished signal!
T’would have to be a powerful harm-inducing agent indeed, to find signal with this systematic error in place! You’d think someone would have noticed this, clinically, at some point…
…unless, of course, the melatonin had nothing to do with it…
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What about Obstructive Sleep Apnea?
And now, for the biggest reveal…the giant in the room that everyone talks about and nobody’s noticing: obstructive sleep apnea.
See, we know for a fact that Sleep Apnea tracks with sleeplessness as well as heart failure. In middle-aged women, insomnia may be the single most common presenting symptom of untreated apnea. According to OpenEvidence.com:[6-8]
For patients who have both congestive heart failure (CHF) and chronic insomnia, the pre-test probability for obstructive sleep apnea (OSA) is likely at least as high as, and possibly higher than, the prevalence seen in CHF alone—approximately 38–54%—and may approach the upper end of this range or higher.
The American Heart Association notes that OSA prevalence in heart failure populations is as high as 40–80%, with most studies reporting OSA in about one-third to one-half of CHF patients. Chronic insomnia is also a recognized presenting symptom of OSA, and among patients with insomnia, OSA prevalence is substantial—ranging from 25–35% for moderate/severe OSA and up to 53–76% for any OSA in sleep clinic populations.
Too much jargon? Let me translate: in the study we’re talking about, it’s statistically likely that Sleep Apnea was very well-represented and utterly un-diagnosed in the melatonin group.
All of this means that, from my lens, it’s quite probable that the melatonin is an innocent bystander, a presumed “safe” agent to use as a way of alleviating symptoms attributable to an overlooked disease that our healthcare system is still too busy to look for in a systematic way.
None of this means the study is bad. It simply means that the rush to condemn melatonin as “dangerous” is premature and wrongheaded--because, like all retrospective studies marred by self-selection, the data set is incomplete.
It means we should be curious, not frightened.
And it means we should not—under any circumstances—let this turn into The Fear of Sleeping Pills Part II: The Revenge of Melatonin.
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The Path Forward
So, what’s a self-respecting evidence-admirer supposed to do?
First, this is a nice reminder that melatonin is not a gummy vitamin. It is a hormone with systemic effects, and chronic high-dose use deserves thoughtful discussion.
We’ll remember to dig deeper into our patient’s narrative of “sleeplessness” using a complexity deconstruction tool like The Five Finger Approach,[9] to help the patient discover root causes for the problem. We’ll take a moment to see “insomnia” as an invitation to explore before we lob a hypnotic at it and hope for the best!
We’ll also keep it in mind, going forward, that insomnia is a serious medical symptom and a marker for poor health outcomes--whether or not melatonin is involved! Self-selection is a major problem in real-world data—those who request and receive medications for insomnia are, by definition, sicker than those who don’t. When we evaluate the science, we must keep these serious systematic limitations in mind before we draw sweeping conclusions.
Mostly, though, we remember that panic is not medicine. Retrospective electronic health record studies are extraordinary tools for raising questions and generating hypotheses, but terrible tools for answering questions about causality.
If you’re taking melatonin, don’t throw your bottle away or sit bolt upright fearing for your heart. Instead, use this moment as an invitation to reflect.
· Why am I using this?
· Has anyone ever thought about the physiology underneath my insomnia?
· Might I have undiagnosed Sleep Apnea or some other problem that’s fixable?
· Is melatonin the right tool for my problem—or simply the only one I knew to reach for?
For clinicians, let this study sharpen our curiosity, not our fear. Let’s reassure patients that association does not prove causality. Let’s help them remember the lesson of 2017: statistical “accuracy” from large datasets showing a difference between groups doesn’t prove causality.
There’s a very good chance these groups started out different, from the word “go”…and that all of this kerfuffle is…wait for it!...
Much Ado About Nothing!
Kind mojo,
Dave
David E McCarty MD, FAASM
Boulder Colorado
17 November 2025
References
1. Shakespeare, William. Much Ado About Nothing. Edited by Claire McEachern, Arden Shakespeare, 2nd series, Bloomsbury, 2015. Act 4, Scene 1, line 18.
2. Nnadi E, et al. Long-term use of melatonin supplements linked to higher risk of heart failure and death. American Heart Association Scientific Sessions, 2025. Preliminary findings summarized in uploaded article.
3. Walker M. Why We Sleep. Scribner; 2017.
4. Kripke DF, Langer RD, Kline LE. “Hypnotics’ Association with Mortality or Cancer: A Matched Cohort Study.” BMJ Open. 2012;2(1):e000850.
5. McCarty DE. “The Story of Dr. Matthew Walker and The Fear of Sleeping Pills.” Dave’s Notes, official blog of Empowered Sleep Apnea, published online June 15, 2022.
6. Yeghiazarians Y, Jneid H, Tietjens JR, et al. Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021;144(3):e56-e67. doi:10.1161/CIR.0000000000000988.
7. Ferrier K, Campbell A, Yee B, et al. Sleep-Disordered Breathing Occurs Frequently in Stable Outpatients With Congestive Heart Failure. Chest. 2005;128(4):2116-22. doi:10.1378/chest.128.4.2116.
8. Lombardi C, Faini A, La Rovere M, et al. Heart Failure and Sleep Related Breathing Disorders: Data From PROMISES (Progetto Multicentrico Italiano Sonno E Scompenso Cardiaco) Study. International Journal of Cardiology. 2018;271:140-145. doi:10.1016/j.ijcard.2018.05.001.
9. McCarty DE. Beyond Ockham’s Razor: Redefining Problem-Solving in Clinical Sleep Medicine using a “Five Finger” Approach. J Clin Sleep Med. 2010 Jun 15;6(3):292-296.