This will otherwise be known as “WTF are you doing, Journal of Medical Hypotheses”.
Sci likes Lithium.
(Lithium burns red. Sci thinks this could have applications for lightsabers if applied correctly)
It’s a cool element, interesting in that we’ve used it over the ages for stuff like gout (which, I hear, is making a comeback), prevention of migraine, blocking the effects of excessive anti-diuretic hormone, and of course for bipolar disorder. But what’s really interesting? We don’t know how it works. Not a clue. It may raise serotonin levels over time, it may decrease or increase other monoamine neurotransmitter levels (such as dopamine and norepinephrine). But we have no idea HOW this occurs. In this, as with other psychiatric drugs (such as Ritalin, which increases dopamine and norepinephrine and improves attention, or with selective serotonin reuptake inhibitors, which increase extracellular serotonin and alleviate depression), we don’t know HOW they work. We just know they WORK (though we’re working on that).
And THAT they work is what matters. When you’re dealing with someone who is potentially suicidal, or unable to function successfully due to severe psychiatric disorders, you’ll take what works and isn’t otherwise “bad” for you (that you can tell), and figure out the mechanism later. And some of these drugs, like Lithium, are very old indeed. Lithium has been used to treat mania and depression since the 1870s, and is still used today as one of the most effective treatments for bipolar disorder (a topic which I SWEAR I will cover someday). It goes a long way toward reducing suicide in those with severe bipolar, and can help with mood stabilization as well.
So if it’s been used that long, it must be good right? This means it might do everyone some good, right? Like, you could put it in the water, and it’d be fine?
Terao, et al. “Even very low but sustained lithium intake can prevent suicide in the general population?” Medical Hypotheses, 2009.
Now, I think we all know that if it’s called “the Journal of Medical Hypotheses”, these aren’t going to be studies which are supported by a lot of data. Really, Sci is not sure why people publish in this journal at all, except for the purposes of giving Sci a good laugh and linking together masturbation and nasal congestion (for the record, I don’t really care if this method works, and I’m not interested enough to obtain IRB approval to find out, but I also don’t worry that it’s dangerous. Well, ok, maybe it is. We all know that some methods of sex are dangerous). I mean, the journal isn’t peer reviewed, and if you know anything about rigorous science, you know that the vast majority of us consider peer review to be pretty essential. So really, it’s probably rare that you’re going to see data sets (though you do see some, but they’re not what I’d call complete). So without data sets or peer review, what do you get? You get the somewhat crack-pot musing of scientists when they are bored or drunk (or both), or perhaps when they are just getting desperate for grant ideas. All of this makes for entertaining reading, but please, I beg you, PLEASE, do not take anything you read in the Journal of Medical Hypotheses as the truth. Even if Sci covers it (if I cover it, chances are I think it’s funny, but I don’t necessarily think it’s true).
But then sometimes Sci sees an article (as she did today), and gets angry. Because in Medical Hypotheses, you can suppose anything. You can suppose Lithium in the drinking water. And this, my friends, is some rank levels of crazy up in here.
The authors of the “hypothesis” are relying on correlations between trace levels of lithium in the drinking water and lower rates of suicide in places like Texas and Oita area of Japan. And certainly, it is very possible that there are higher rates of lithium in these areas, and lower rates of suicide. They also note data that even bipolar patients who do not respond well to treatment have lower levels of suicide than those who are bipolar and not treated with lithium. So it appears that lithium treatment correlates with a lower risk of suicide in depressed and non-depressed populations. Got it? Good.
Now let’s all take a big, deep breath, and talk about how correlation does NOT equal causation, and about how anecdotes are NOT data. Good? Good.
And now let’s come back. There are a LOT of things outside of lithium levels in the drinking water that could correlate with lower rates of suicide in any given area. These could include higher overall rates of mental health, higher rates of treatment for psychiatric disorders, differences in socio-economic status, differences in religion, etc, etc, etc. And as far as bipolar patients, those who are NOT on lithium may have been poor responders. They may also be unmedicated. Both of these things increase the risk of suicide in bipolar patients. Those who are not on lithium may not be receiving as much or as frequent care and follow-up as those on lithium. And one can never discount the placebo effect on mood, it is possible that simply KNOWING you are treated can help you get through some of the more difficult bipolar periods.
But yet. Three studies, all of them correlations, and they want to put lithium in the drinking water. But hey, you might think, lithium’s a naturally occurring ion, right? What’s the problem?
Well, lithium is indeed naturally occurring, but it’s usually in things. Occurring alone as an unbound ion or in the salt form as it is given in the clinic is really pretty rare. It’s a very fragile element, and highly reactive, so it’s going to bind to things. So even getting IN to the water in a therapeutic form is going to be a challenge. That’s problem number one.
Problem number 2 is dosing. Lithium is a VERY hard drug to dose. It’s hard to keep drug levels in a constant therapeutic range, and even harder to FIND that therapeutic range in some individuals. There is no proof that low doses below therapeutic range would have any promising effect on the population (except for those two correlative studies). Additionally, there’s no proof that lithium can decrease suicide rates among those without psychiatric disorders. And while in low doses it can be a mood stabilizer, and in higher doses can combat forms of mania, it’s VERY hard to get those doses right without running into side effects. This is what we call a narrow therapeutic range, and the therapeutic range of lithium is notoriously narrow.
So what are those side effects? Here we get to problem number 3. Luckily, lithium is not deadly in therapeutic doses. The most common side effect is weight gain, which, though not something society needs more of, is more of a long term threat than an immediate one. But another very common side effect is decreases in thyroid hormones.
For those who don’t know a lot about thyroid hormones, these are hormones that control metabolism regulation, especially things like weight gain, energy level, and body temperature. Lithium tends to reduce the activity of thyroid hormones, and can cause hypothyroidism, resulting in constant fatigue, constant feelings of cold, increases in appetite (weight gain), constipation, hair loss, and depression.
But it doesn’t stop there. Lithium can also have effects on the kidney, causing you to excrete too much sodium and water, and causing dehydration. Dehydration can concentrate lithium levels, which of course can make this worse.
The net result of all these is that patients on lithium must be monitored for their blood levels on a regular basis, to check for kidney and thyroid function, as well as other side effects like weight gain and changes in potassium levels. Not only that, lithium, as I mentioned before, likes to bind to things. This means it also can interact with other drugs. Due to its effects on the kidney, it should NEVER be taken by those who are being treated with diuretics (for things like hypertension, diuretics are a first-line treatment. Lithium has also been known to react very badly to other psychiatric drugs such as haloperidol and other antipsychotics.
Now, constant measurement in people who are bipolar and on lithium is necessary. It’s not fun, but it’s the drug that works, and for those people, the side effects are often worth it.
But you want to put this in the drinking water?
Now, granted, the authors say they want to use really low doses. But HOW low? If a dose is low enough, it won’t have any effect at all. And remember, lithium has a VERY low therapeutic range. What’s barely detectable in a grown man might be a big deal in say, a small child or woman. Not to mention the possible combined effects in people who actually ARE on lithium at therapeutic levels. And what about possible interactions with the millions of people on diuretics, or the people on antipsychotics? The side effects of lithium in combination with antipsychotics can be pretty toxic, is there a dose low enough that would even make sense?
I think you can tell where Sci is going with this. This is a bad idea. At best, it’s a potentially useless idea, and at worst, it is bad indeed. For hypotheses like these, founded on the bare minimum of evidence and with little regard for things like negative side effects, Sci proposes a new journal. Sci will be editor. Now accepting submissions for “The Journal of Delirium Noctourne.”
Terao, T., Goto, S., Inagaki, M., & Okamoto, Y. (2009). Even very low but sustained lithium intake can prevent suicide in the general population? Medical Hypotheses DOI: 10.1016/j.mehy.2009.02.043