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Day # 53: Lithium (part 2) -> Drug Levels, Interactions, and Lab Monitoring.

Today we are going to continue our discussion about lithium. In our first post about lithium we discussed mechanism of action, evidence, and indications. Today we will discuss how the body eliminates lithium, the importance of drug levels and interactions, and important laboratory tests in patients taking lithium long-term.

Today’s Content Level: Beginer, Intermediate, Advanced.


  • Lithium is an element and is not metabolized in the body. Instead it is primarily excreted by the kidneys where it is handled similar to sodium.

  • Following glomerular filtration, the majority of lithium (60%) is reabsorbed in the proximal tubule along with sodium.

  • This concept is important for understanding how certain pathophysiologic states (dehydration, CHF) and medications (thiazide diuretics) can increase renal lithium reabsorption and precipitate toxicity.

  • Half life is 20 hours. Therapeutic serum drug concentration achieved in 5-7 days. This is why it is often recommended to add an antipsychotic +/- a benzodiazepine for the urgent treatment of acute mania.


  • Lithium has a very narrow therapeutic window. There is a small difference between therapeutic effect and toxicity. Signs of lithium toxicity include GI distress, tremors, and edema. More on this in the next lesson.

  • For this reason, obtaining serum concentrations is necessary.

  • Recommended drug concentrations for acute treatment is 1-1.5 mEq/L and for maintenance treatment is 0.6-1.0 mEq/L. 1

  • Initial monitoring: every 1-2 wks until desired serum concentration is achieved, then every 2-3 months for the first 6 months. Then every 6-12 months unless there is a dose change.


Drugs that increase lithium levels (decrease renal lithium clearance):

  • Thiazides (increase PCT lithium reabsorption)

  • ACE inhibitors (decrease GFR)

  • NSAIDs except aspirin (decrease GFR)

  • Tetracyclines

  • Metronidazole

Other factors that increase lithium levels:

  • Sodium restriction

  • Dehydration (heavy exercise, hot weather, saunas, vomiting, diarrhea, fever)

Drugs that decrease lithium levels:

  • Caffeine

  • Potassium sparing diuretics (eg, amiloride)

  • Theophylline

Combination of lithium and the following medications can sometimes lead to neurotoxicity and lead to delirium, cerebellar dysfunction, extrapyramidal symptoms, and severe tremors:

  • Antipsychotics

  • Carbamazepine

Serotonin syndrome

  • Increases risk of serotonin syndrome when combined with other serotenergic agents.


•Our next post will cover lithium's early side effects, long-term side effects, toxicity, and management of these symptoms. It probably makes more sense to include laboratory testing in that section, but that post is already long so I'm including it here. If it doesn't make perfect sense why some of these tests are included then reference the next post.

Prior to starting lithium the following tests should be obtained:

  • Thyroid function studies (lithium can cause thyroid dysfunction)

  • Serum calcium (lithium can cause hyperparathyroidism)

  • Kidney function studies (Urinalysis (UA), BUN, Creatinine) (lithium can cause nephropathy)

  • +/- ECG - in patients at risk of cardiac disease or those older than 50 yo.

  • +/- Pregnancy test - in women of childbearing potential. (lithium can be teratogenic, however risk is historically overestimated).

Other tests worth considering:

  • Basic Metabolic Panel (BMP) ->electrolytes -> sodium, potassium, glucose.

  • Complete Blood Count (CBC) (lithium can cause benign leukocytosis).

  • Hemoglobin A1c, fasting lipids (lithium can cause weight gain).

Serial monitoring for patients taking lithium long-term should include:

  • Thyroid function studies: 1-2 times in the first 6 months. Every 6-12 months thereafter.

  • Serum calcium: annually.

  • Kidney function studies (Urinalysis (UA), BUN, Creatinine): 2-3 times in the first 6 months. Every 6-12 months thereafter.

  • Other tests as clinically indicated.


Today was part 2 of our discussion of lithium. Next lesson will be part 3 and our last day to cover lithium. We will cover early side effects, long-term side effects, toxicity, and management of these symptoms.

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