Pleae dose lithium just once daily – Really.

by | Jul 3, 2023 | Curbside Consults

Question:

Dr. Ghaemi recommends Lithium once daily dosing over twice daily to minimize renal side effects, based on studies like this one:
Singh, Lokesh Kumar, et al. “Improving tolerability of lithium with a once-daily dosing schedule.” American Journal of Therapeutics 18.4 (2011): 288-291.

What are your thoughts on this article that recommends twice daily dosing:
Mendelsohn, Alex. “Lithium story: eight guidelines, eight recommendations.” The Lancet Psychiatry 10.5 (2023): 321-322.

PL:

This essay above is written by a patient in the UK who is a physicist. He makes a big deal about the pharmacokinetics of lithium, but what he and most doctors don’t understand is that the pharmacokinetics of lithium is measured in the blood, which is completely irrelevant to the brain. (By the way, the essay consistenly and falsely states that lithium half-life is 12 hours; that is wrong. For most people it is about 24 hours. For older persons, even longer. But as noted below, it doesnt really matter in relation to clinical efficacy).

It takes lithium months to years to have its second messenger effects in the brain, which is its mechanism of action. Its hour to hour variations in the blood are completely irrelevant to this months or longer brain mechanism.

Blood levels are relevant to kidney harm. A stable blood level – which is irrelevant to the brain – is worse for the kidneys because they consistently get a stable (and high) level. If dosed once daily, the kidneys receive a short peak and then a long trough of lithium, overall at a lower level of exposure. This effect is consistent with the clinical literature in multiple studies (not just the one above) which clearly shows more long-term chronic renal insufficiency with multiple daily dose of lithium versus once daily dose.

So both for the brain and the kidney, it is unnecessary and even harmful to dose lithium more than once daily.

It is hard to understand why this simple fact is so completely misunderstood by the clinical community. Part of this misunderstanding may have to do with the fact that most clinicians simply don’t understand the second messenger mechanisms of action of lithium in the brain, and their slow disease-modifying clinical effects.