Melatonin, Zinc, and Vitamins for Coronavirus: It's Pascal's Wager All Over Again

“It’s safe, why not try it?” is a good argument for any ONE drug. But it falls apart quickly.

Things are getting a bit bleak here in New Haven. While my hospital has not reached the peak we saw in April – with 450 COVID+ inpatients, we’ve started going up pretty dramatically – from a nadir of just a handful of patients to the current COVID census of around 150.

I’ve taken care of these folks both on the renal consult service and as the general internal medicine attending and one type of question comes up a lot:  Doc – why can’t you give me [blank]?

Now – “blank” depends a lot on the patient. For some, the blank is replaced with one of the few proven COVID treatments – dexamethasone or remdesivir. For most, though, blank is replaced by something that has been in the news a lot – hydroxychloroquine, Vitamin D, Vitamin C, Zinc, melatonin.

These are tough questions for me. Usually, in medicine, we talk about risk versus benefit of given treatments, but – COVID-19 makes the calculus more difficult. The outcomes can be so bad, and we really don’t have any slam dunk treatments yet. For some, this evokes the “right to try” movement – the idea that, when the situation is dire (like in terminal cancer) – we should be allowed to try unapproved drugs because, what’s the harm?

And, to be fair, a lot of the treatments people ask about for COVID are low risk. While I lecture about the risk of oxalosis from vitamin C intoxication, I can’t say I’ve seen a single case.

And yet I’m hesitant to give my patients any of these medicines, because, as I’ve discussed here several times, there isn’t robust evidence for efficacy.  No good, randomized trials to show me this stuff actually works.  Still, I found it difficult to explain my reasoning, until I remembered about Pascal’s wager.

Pascal’s wager in epidemiology table form

Many of you know of this idea, but brief recap.  In the mid 1600s, Blaise Pascal argued that the rational person should choose to believe in god.

It works like this – if god exists, you should believe in him. Because if you don’t you’re in a world of pain (literally) and if you do you receive infinite reward (whatever that is). If he doesn’t exist, well, it doesn’t really matter if you believe one way or the other. But clearly, game theory argues for belief.  Hedge your bets, right?

Pascal’s melatonin wager

It’s the same deal when we’re talking about, say melatonin.

It may not work, in which case, the harm from taking it is pretty small – you get a little sleepy. But if it does work – well, it may save your life.  All that is wasted by believing in melatonin, or zinc, or whatever, is the cost of the pill and some generally mild side effects – maybe the occasional anaphylaxis.  So why not use them?

But what if god is Odin???

Of course, since Pascal made his famous wager there have been plenty of folks who have offered counterarguments. And those counterarguments actually translate directly into the practice of medicine in the era of COVID-19. Go with me on this.

One classic refutation is called the argument from inconsistent revelations. Put simply, what if you pick the wrong god?  Maybe you’re worse off worshiping Pascal’s God if, in reality, Odin is behind it all, and would be ok with an atheist but pretty upset about someone spending all that faith worshiping someone else.

For COVID-19, the analogy is clear. What if you pick the wrong medicine?  What if while you’re wasting time treating someone with melatonin, zinc was the silver bullet the whole time?  Sure, we could throw the book at the patients – a la Trump at Walter Reed – but what if certain meds counteract the effect of others?

We just don’t know.

Pascal’s wager only really works if there is only the possibility of one god – in medicine, it only works if you’re only thinking about one medicine.  If my patient wants hydroxychloroquine, I could give that to them thanks to Pascal, but I could do the same for the patient asking for Vitamin D, and the patient asking for Zinc, and the patient asking for some cocktail of all of the above. 

How do we decide?  Well – of course – we are in a much better place than Pascal was. Pascal’s god famously does not like to be tested, but medications do not need to be taken on faith.

We can conduct rigorous clinical trials and figure out whether, you know, heaven exists.

I’m not sure if this explanation makes it clear why docs like me – who, to be fair, conduct clinical trials – are so obsessed with clinical trials. Pascal’s wager is a decent argument to use with any single medication. The problem is – it works with all the medications, which makes it really quite useless as a decision tool. Thank god we have better tools to figure out the truth. They’re called randomized clinical trials.

This commentary originally appeared on medscape.com.