3 ms·

That monograph is not appropriate to this discussion because it is written for practitioners, not researchers. There is plenty of information on some of the thi

That monograph is not appropriate to this discussion because it is written for practitioners, not researchers. There is plenty of information on some of the things lithium is doing. My point was not "we have a complete understanding", but "we have some idea what is going on here, but there is still a lot we don't know". Lithium is one of a large class of drugs that modulate the chemical potentials of the body's voltage-gated ion channels. There are a lot of drugs in this class, and most have been used with at least some degree of success to treat bipolar disorder. This class is also first-line treatment for many forms of epilepsy. The GABA system is directly tied in here too, and GABAergic agents are generally considered part of this class... and, guess what, they often help in bipolar as well. Lithium is a unique member of this class, and it is completely obvious (to a biochemist) that adding another species of alkali metal in sufficient concentration will disrupt the chemical potentials of sodium and potassium ion transport in the ion channels. My point is: the first-level effect of lithium is well understood, and it affects an area that is well known to be affected by other drugs that have similar effects. So it is not total voodoo. However, you are also very correct that our understanding starts to break down after this. We can come up with new ion channel modulating drugs, and can reasonably expect them to be effective candidates for helping bipolar patients. What we cannot do is predict other targets or classes of drugs that might be interesting. That is where our understanding breaks down.

owenversteeg 1y ago
I'm not sure why the relevant portion of the monograph isn't appropriate simply because of the target audience. "Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown" is the general consensus on lithium whether you're reading it as you, me, or Donald Duck. Here is where we can both agree: we know a few things about the mechanism, which allow us to make some useful judgments in a few limited cases. We can also both agree that we know so little that, if a new, similar drug were proposed, with only a small change to its chemical structure, neither of us would dare make any confident statements about its action. We also cannot accurately predict what would happen if given to a patient with a well-studied but different disorder. In other words: most of the useful judgments about lithium - those that would be economically or socially interesting, for example - cannot be made from the model, because our understanding of the mechanism of action is too crude. All of that is also, however, true about my hypothetical Corolla from my first example: we can say a few things, but most of the useful judgments that could be made from a full understanding cannot be made. It would be obvious to anyone that we do not understand the Corolla. So why, then, would we claim to understand lithium?

owenversteeg 1y ago

I'm not sure why the relevant portion of the monograph isn't appropriate simply because of the target audience. "Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown" is the general consensus on lithium whether you're reading it as you, me, or Donald Duck. Here is where we can both agree: we know a few things about the mechanism, which allow us to make some useful judgments in a few limited cases. We can also both agree that we know so little that, if a new, similar drug were proposed, with only a small change to its chemical structure, neither of us would dare make any confident statements about its action. We also cannot accurately predict what would happen if given to a patient with a well-studied but different disorder. In other words: most of the useful judgments about lithium - those that would be economically or socially interesting, for example - cannot be made from the model, because our understanding of the mechanism of action is too crude. All of that is also, however, true about my hypothetical Corolla from my first example: we can say a few things, but most of the useful judgments that could be made from a full understanding cannot be made. It would be obvious to anyone that we do not understand the Corolla. So why, then, would we claim to understand lithium?