Lithium, as everyone knows, is a song by Nirvana. (It's also a different, and worse, song by Evanescence). It's also a chemical element. And it's a drug, used in psychiatry to treat bipolar disorder and, sometimes, severe depression.One thing which lithium seems to do rather well - or at least better than other drugs - is make people less likely to commit suicide. At least, that's what most authorities say, so let's assume it's true.
Now a Japanese team report that the amount of lithium in tap water are negatively correlated with suicide rates - Lithium levels in drinking water and risk of suicide. (Someone has helpfully put this up on Scribd for people without academic access).
They analyzed the water supplies in the 18 subdivisions of Oita prefecture in southern Japan, and compared the lithium levels in the water with the average suicide rate (normalized for age and gender). Here's what happened -
Now, on paper that's a pretty solid correlation. But how believable is it? The maximum lithium level in the water was found to be 59 micrograms per liter. By contrast, if someone were taking lithium for bipolar disorder, they would on average be taking about 1 gram of lithium carbonate (Li2CO3) per day, which works out at about 100 mg of lithium (and 900 mg of inert carbonate).Assuming that people drink about two liters of tap water per day (almost certainly they drink less), that's about 120 micrograms per day. That's 0.12 mg. So about a thousand-fold less than you'd take if you were bipolar.
Could such a tiny amount of lithium do anything? Well, maybe. It's not impossible that it would have some small effect on suicide rates, but it seems very unlikely that it would account for the difference between a rate of 120 and a rate of 80 which is what the graph seems to imply. The effect is just too large to be credible, if you ask me.
Although that said, another paper just out found that tiny amounts of antidepressants (the amounts that you find in rivers because so many people take them and some of them are stay in urine) could affect the behaviour of baby fish. And presumably also baby humans. Unfortunately I can't access this study, so I don't know whether that's nonsense or not, but it's food for thought.
Ohgami, H., Terao, T., Shiotsuki, I., Ishii, N., & Iwata, N. (2009). Lithium levels in drinking water and risk of suicide The British Journal of Psychiatry, 194 (5), 464-465 DOI: 10.1192/bjp.bp.108.055798
19 comments:
Fascinating!
One thing though: phrases like "it seems very unlikely" and "the effect is just too large to be credible, if you ask me" sound an awful lot like arguments from incredulity...
Well, it pretty much is... if these data are to be believed lithium levels in drinking water account for a large % of the variation in suicide rates in Japan. Which is just hard to believe given all the other factors that must also affect suicide rates.
It's too good to be true...
So much for the British Journal of Psychiatry. I guess it must be pretty "prestigious" to sit on its editorial board.
I will refrain from expressing -in sincere terms- my opinion about the article. Probably I suffer from "adult selective mutism."
If it is true, does that imply that people taking lithium for bipolar could do with a much lower dose?
I'm not saying the BJP shouldn't have published it. although if I'd been a reviewer I'd have made them spell out just how small the amounts of lithium were. It's a quite interesting claim.
Seems like this might become a game of "spot the confounder" to me.
I don't know what psychosocial and environmental factors would be associated with living in an area where there is a high lithium content - have factors like deprivation or socio-economic status been taken into account?
Does the study take the number/rate of lithium prescriptions into account?
I fear that only taking sex and age into account is probably not sufficient. Sounds like there are a whole host of factors unaccounted for in this analysis.
Ah well, without an expert knowledge of the Japanese water system I don't think we know what possible confounders there might be. And I'm proud to say I know nothing about that.
Although the idea that springs to mind is that rural water supplies might have different lithium levels to urban ones. And suicides also tend to differ between rural and urban areas.
Well, as we all learn in our first stats course: correlation is not causation. It makes me wonder what else in the water that might affect suicide rates...
Customer:"Waiter! There's Lithium in my soup"
Waiter: "Quite possibly madam, but not enough to make any difference to the quality of your eating experience at this restaurant"
P.s. As someone who is still in the pending file for being prescribed Lithium..that is pending several areas of concern that need addressing first, any info on whatever evidence(properly researched) there is in regards to Lithium efficacy/side effects is alright by me.
I love that album! Another great post! Keep up the good work!
I don't think this paper can be considered anything more than simply hypothesis generating.
This is about the lowest quality level of epidemiological data possible - they use aggregated data for different regions and adjust purely for gender and age distribution (by using SMRs).
Incidentally - is it just me that can't see how that figure shows a gradient of -.65 - I make it about -.2 - the reason I was wondering is because I wanted to project how much of a suicide reduction we should expect for therapeutic doses of lithium assuming this log-linear relationship - the ref in the paper says 8-fold which wouldn't be incompatible with my reading of what the regression should look like (giving an SMR of 25).
What am I doing wrong in reading the figure? It is definitely log base 10 (log(59)=1.8 which is the rightmost data point)) and it can't be the transformed beta coefficient because that couldn't be negative - although 10^-.2 = .63 which is close to .65.
Well spotted. Could it be that they did something weird to try to express the regression coefficent in terms of Li rather than log-Li?
Well that was what I was thinking but I can't quite figure out what.
Their equation is of the form
y=b.log(x) + a
but that isn't something like a logistic regression so you can't just do 10^b to find the equivalent slope on x.
Looking at the figure it seems that an equation something like
y=-.2*log(x) + 1.2
would fit, but I don't see that we can meaningfully convert that beta back into linear space (you can do this for logistic regression because the beta has an intepretation that means the odds ratio is multiplied by exp(b)) since it isn't like logarithms have been taken on y (although, thinking about it - I would think that would be a better way of treating the SMRs) because the regression line one the graph is linear for y.
But maybe I'm just being a bit dim today and someone else can explain it to me.
Many have defined Bipolar Disorder (manic-depressive illness) as being major affective mood disorder in which one alternates between the mental states of deep and brutal depression with embellished and inflated elation.
These mental states can last for months in some bipolar disorder patients. These cyclical episodes are a catalyst for noticeable psychosocial impairment.
Also, the episodes of both manic phases as well as depressive ones can last anywhere from weeks to months.
Bipolar Disorder also affect’s one’s cognition, emotions, perceptions, and behavior- along with psychosomatic presentations (such as pain with depressive episodes, for example).
It is thought to be due to a physiological dysfunctional brain in one affected with bipolar by many.
The etiology for bipolar disorder is unknown. As many as half of those suspected as having a bipolar are thought to have at least one parent with some sort of mood disorder similar to bipolar disorder, which suggests a genetic predisposition may be present.
Because of the complexity associated with bipolar disorder, greater than 50 percent of those afflicted are misdiagnosed as major depression, or perhaps schizophrenia.
It is also believed that bipolar presents itself with symptoms associated with the definition of bipolar when one is between the ages of 15 and 25 years old.
The disorder was entered in the psychiatrists’ bible, the DSM, in 1980, although bipolar disorder is thought to have existed for quite some time.
Also, those with bipolar are thought to be in possession of heightened creativity during their manic phases, as well as they have accelerated growth of their neurons.
This is not necessarily a bad thing, it seems. Conversely, those with bipolar disorder experience up to 3 times the number of depressive episodes as manic ones.
Research has determined that as many as 15 to over 30 percent of bipolar patients commit suicide if they are left untreated, or undertreated.
Also, as many as half of those affected with bipolar also have at times severe substance abuse issues along with their bipolar as well.
Co-morbid medical conditions should be taken into consideration when evaluating one suspect of, or having bipolar disorder.
Bipolar patients are also often experiencing anxiety issues that vary, and are treated often as a result of these medical issues.
The disorder varies as far as severity goes- with some bipolar patients being more severely affected than others.
In fact, there are at least 6 classifications of bipolar, according to the DSM.
Bipolar patients are thought to be symptomatic half of their lives. As stated previously, the depressive episodes occur more frequently than manic ones.
When symptomatic, bipolar patients are thought to be rather disabled, according to some, when in their depressive state in particular.
The diagnosis has become more frequent recently. In one decade, the assigned diagnosis of bipolar rose from being about 25 per 100 thousand people to being 1000 per 100,000 people.
Most diagnosed with bipolar are not diagnosed based on solid, comprehensive, or psychiatric review that is often absent of valid or standard diagnostic methods.
Some believe as many as 5 percent of the human population may be affected by bipolar disorder- which may include as many as 12 million people in the United States.
This is if the diagnostic criteria developed by others were to be fully utilized. An emphasis should be implemented by the health care provider to utilize available clinical evidence, and review this scientific literature.
A subjective questionnaire called the Mental Status Examination is often utilized when diagnosing one suspected has having bipolar disorder.
Many believe the diagnosis has increased recently due to the progressive treatment options now available. It is an argument of increased awareness versus over-diagnosis.
Yet the diagnosis is vague, as children and adolescents are often absent in research with bipolar. Also, there is not any objective diagnostic testing to rely upon for bipolar.
There is also a mental diagnosis of what is called mixed depressive disorder, which is one with depression who also has minimal manic episodes.
Many younger than 18 years of age are prescribed atypical anti-psychotics as first line treatment, which is largely not recommended as treatment options.
In fact, possibly close to half a million of those younger than 18 years of age are prescribed the atypical anti-psychotic Risperdal alone, it has been determined.
The class of medications overall is thought to be prescribed to about 10 percent of those non-adults thought to have bipolar.
While not recommended, about a half of all those assessed as being bipolar are prescribed antidepressants, such as SSRIs, as first line treatment.
It has been suggested that this class of drugs has decreased the risk of suicide attempts compared with other classes of antidepressants for close to 20 years.
Yet tricyclic antidepressants have been determined to be efficacious in over half of those diagnosed with bipolar - with a greater amount of research behind this class of drugs.
Furthermore, therapy with any antidepressants has been associated with what is known as treatment-emergent mania.
This is when a bipolar disorder that is in a depressive state rapidly enters a manic phase.
This occurrence can be unmanageable by the bipolar disorder patient.
The most recognized treatments for bipolar long term are lithium (Ekalith or Lamictal- along with an anti-convulsant. Sugar intake is thought to vex the symptoms of one with a bipolar disorder as well.
Atypical anti-psychotics have been prescribed for bipolar, which change some aspects of the brain, physiologically, as does the disease itself.
In fact, one may argue the brain becomes more efficient due to both the disorder and the treatment with the atypical anti-psychotics.
Yet many recommend the utilization of this class of drugs with bipolar disorder only if psychosis is present as well.
As many as 15 percent of bipolar disorder patients diagnosed as such are prescribed an atypical presently. This class of medications may be particularly beneficial for those women who are diagnosed with bipolar who are pregnant, however.
Lithium, which is essentially a very light metal with low density in which the salts are obtained for medicinal treatment, and an anti-convulsant are believed to be standard bipolar treatment, pharmacologically, studies have shown.
This is due to Dr. John Cade and his examination with lithium and its benefits with those who have psychotic excitement close to 60 years ago.
Ekalith is believed to be both neuro-protective as well as having an anti-suicidal affect in those believed to be bipolar- and is viewed as a mainstay as far as treatment for bipolar goes with many who treat the disorder.
Lithium is thought to regulate the calcium molecule in the brain, so this and valporate are historically the medicinal treatment options preferred for those with bipolar disorder.
Bipolar is difficult to detect, and is often diagnosed as major depression with many affected by this disorder.
There is no objective criteria protocol available to utilize when assessing any patient believed to be suffering from any mental disorder.
So such mental disorders that are diagnosed are ambiguous, yet that does not conclude that such disorders do not exist, such as the case with bipolar disorder.
Yet perhaps a health care provider should be very thorough and knowledgeable when assessing a patient believed to have a mental condition such as bipolar.
As should the health care provider keep in mind that the ultimate goal with this disorder is to stabilize the mood of the one affected.
www.dbsalliance.org
Dan Abshear
Author’s note: What has been annotated is based upon information and belief.
If you check the nutritional literature you'll find evidence that lithium at low levels is an essential nutrient:
http://www.jacn.org/cgi/content/full/21/1/14
The above article suggests an RDA of 1mg/day for an adult human.
Huh, I didn't know that. But presumably there's lithium in food, right, so it's not as if we rely on lithium in water for our needs?
There is some in food, some in water, so it depends. My point is just that the nutritional requirement is indeed about a thousand times less than the typical antimanic dose, which makes the results of the epidemiological studies less surprising -- just a little bit in your water might make the difference if there isn't enough in your food.
The lithium in food thing has been raised in two Letters in the latest BJP (1,2) and the Author's Reply (3).
They refer to an Indian study finding "levels as high as 12 µg/g of lithium in tobacco and high levels in crude salt, rock salt and several spices."
"There is some in food, some in water, so it depends. My point is just that the nutritional requirement is indeed about a thousand times less than the typical antimanic dose, which makes the results of the epidemiological studies less surprising -- just a little bit in your water might make the difference if there isn't enough in your food."
So when talking about "natural" does, we should be looking at quantities measured at the microgram scale, NOT the milligram.
So, suddenly, it sort of makes the Japanese study less... quacky?
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