What does this picture have to do with lithium? AND: new monitoring recommendations for lithium

Do you know what this picture may have to do with lithium and drug interactions? Also, learn of an easy new screening test and other lithium monitoring recommendations from a Lancet review so hot off the press that it’s still in press!

First, the picture. In drug interaction talks, I like to ask how lithium is metabolized. It’s a trick question: you can’t break down lithium (or modify bonds, add moieties…) because it’s an element…and your liver isn’t nuclear! It’s also a good reminder that there are many things (not just metabolism!) that can affect Rx levels and toxicity. These include other pharmacokinetic effects*; pharmacodynamic effects; and idiosyncratic interactions.**

Lithium is an element (not a molecule). See?

Second, the easy but important screening test: The new Lancet article, Lithium toxicity profile: a systematic review and meta-analysis (full text via UW) recommends serum calcium be checked before and during treatment. Why? Because in addition to hypothyroidism, a risk of lithium therapy is hyperparathyroidism. Serum calcium the appropriate screen for this (you don’t need to check PTH).  Below is a summary of lithium monitoring recommendations from the article.

Notable lithium therapy recommendations from the Lancet article

Before starting lithium

  •     Baseline tests: at least GFR, TSH, calcium
  •     Explain uncertainty about risk of congenital malformations

During lithium therapy

  • GFR, TSH, calcium at least every 12 months [more frequently if any abnormalities or family history of endocrine disease]
  • Repeat blood tests immediately if change in mood state (eg, mania).
  • For women who are or would like to become pregnant: advise that increased risk of congenital malformations is uncertain; discuss the balance of risks between harm to the baby and maternal mood instability before making a decision to stop lithium


Bonus: An accompanying editorial, Is the safety of lithium no longer in the balance? (full text via UW), joins a continuing chorus of opinion supporting that lithium is effective and not as likely to cause problems as is generally thought. They include a picture of the “lithiumeter” from the cleverly-named paper, The Lithiumeter: a measured approach (full text via UW) which visually summarizes recommended levels for different stages of lithium therapy and risks/toxicity along the scale. However, I wonder whether the depression “maintenance” level might be capped too low and will be asking a mood disorders expert about this (will discuss in a future post).

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* pharmacokinetic effects are generally categorized in the ADME model: Absorption [eg, GI acidity and P-glycoprotein effects], Distribution [eg, protein binding], Metabolism [P450 and other enzymatic modifications], Excretion [eg, elimination via urine/feces]

** Lithium has an unusually large number of “idiosyncratic” reactions. Examples of potential interactions of other Rx with Li: neuroleptics → “NMS-like syndrome”; carbamazepine → delirium; neuromuscular blocking agents → ↑ toxicity of these agents; and a number of Rx (SSRI, methyldopa, carbamazepine, phenytoin, CCBs) → ↑ Li toxicity

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