Lithium

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Background Information1

Lithium is the lightest known metal. It is rather soft in its natural state – to the point it can be cut with a knife! Lithium can be used in several different ways:  batteries, manufacturing and medications. It’s even makes up a small percentage of the Earth’s crust. Lithium is typically found as compounds, not just a free element. These are typically known as Lithium salts and are most commonly used to treat Bipolar Disorder (BD) and mania, and they were the first drugs to be approved by the FDA to do so. The video below dives a little deeper into how Lithium helps treat Bipolar Disorder.

 

Mechanism of Action1,4

Even though Lithium has been used to treat mental health disorders for decades, the mechanism of action is still unknown. There are scientists that have their theories though – some believe that therapeutic action may be due to the inhibition of glycogen synthase kinase 3, inositol phosphatases or modulation of glutamate receptors. Many have drawn the conclusion that glutamate is the key factor because Lithium has been shown to change the inward and outward currents of the glutamate receptors. This allows Lithium to keep glutamate levels between cells at a stable, healthy level.

A cool study at MIT using worms showed that Lithium inhibits key proteins in the brain for making neurons linked to avoidance behavior. The results from this study suggests that Lithium has the ability to silence certain neurons in the brain and stimulate a calming effect. This very well maybe one reason it works so well to treat mania and depression.

Toxicokinetics2,3,6

Lithium absorption is rapid and its bioavalibility is close to 100%. The kidneys excrete the vast majority of Lithium from the body at a whopping 95%. The other 5% tends to be removed via sweat and feces. The serum elimination half-life can vary quite a bit and is roughly 12-27 hours. Lithium is known to cross the placenta and can be found in breast milk as well. The main targets for Lithium include the brain, kidneys, liver, bone, muscle and thyroid, as shown in figure 1 below. Patients that are prescribed Lithium usually have a dosage between 900 and 1200mg per day, and a safe blood level is ranges from 0.6 to 1.2 mEq/L.

Figure 1. Targets and Symptoms of Lithium Toxicity

 

Signs and Symptoms of Toxicity2

Toxicity can vary quite a bit depending on the amount of Lithium present in the blood. Toxicity typically starts at around blood levels of 1.5 mEq/L, are considered severe at around 2.0 mEq/L, and are a medical emergency at 3.0 mEq/L or greater.

Mild symptoms include:

  • diarrhea
  • vomiting
  • stomachache
  • fatigue
  • tremors
  • muscle weakness
  • uncontrollable movements
  • drowsiness
  • overall weakness

Severe symptoms include:

  • heightened reflexes
  • seizures
  • agitation
  • slurred speech
  • kidney failure
  • rapid heartbeat
  • hyperthermia
  • uncontrollable eye movement
  • low blood pressure
  • confusion
  • coma
  • delirium
  • death

Toxicity can be classified as:

  • acute:  when too much Lithium is taken at one time
  • chronic:  when a little over the prescribed doses is taken daily over a long period of time
  • acute-on-chronic:  when Lithium is taken as prescribed over a long period of time but an extra dose is taken one day

Toxicity can also depend upon dehydration, other medications and other medical conditions such as kidney problems.

Treatments2

There is no specific antidote for Lithium toxicity.

Mild toxicity normally resolves on its own when the patient is given extra fluids.

Moderate/severe toxicity treatments:

  • stomach pumping (within an hour of ingestion)
  • whole bowel irrigation
  • IV fluids
  • hemodialysis

Medical personal may prescribe anticonvulsant medications if the patient starts to seize. Activated charcoal is not a viable treatment option due to the fact it will not bind to Lithium.

Susceptibility2,3 

Older patients might be more sensitive to Lithium and experience side effects at lower doses. They may be at a higher risk for:

  • metabolic syndrome
  • cardiovascular diseases
  • general renal diseases
  • cognitive decline

Pediatric patients may experience:

  • suicidal ideation
  • changes in blood cell counts
  • neurological side effects

Those taking other medications can have an increased risk of Lithium toxicity. Those medications include:

  • NSAIDs
  • cox-2 inhibitors
  • indomethacin
  • acetaminophen
  • metronizdazole
  • calcium channel blockers
  • ACE inhibitors
  • diuretics

Concentrations of Lithium found in the blood is also effected by different foods and drinks.

Essentiality/Deficiency1,5

There isn’t an essentiality or deficiency tied to Lithium per se, however, it has been found that those who have Lithium “deficiency” can exhibit unstable moods, agitation and increased rates of suicide/homicide/violent acts. There is also data that shows populations with low levels of Lithium naturally occurring in their drinking water have lower levels of overall depression and mania as well as lowered suicide rates.

 

References

1. Pappas, Stephanie. “What Is Lithium? | Live Science”. Livescience.Com, 2018, https://www.livescience.com/28579-lithium.html. Accessed 15 June 2021.

2. Cafasso, Jacquelyn. “Lithium Toxicity: Levels, Signs And Symptoms, Causes, And Treatment”. Healthline, 2018, https://www.healthline.com/health/lithium-toxicity. Accessed 15 June 2021.

3. Volkmann C, Bschor T and Köhler S. (2020) Lithium Treatment Over the Lifespan in Bipolar Disorders. Front. Psychiatry 11:377. doi: 10.3389/fpsyt.2020.00377

4. “Lithium Cation: Uses, Interactions, Mechanism Of Action | Drugbank Online”. Go.Drugbank.Com, 2021, https://go.drugbank.com/drugs/DB01356. Accessed 15 June 2021.

5. Martone G. Nutritional Lithium. J Clin Psychiatry Neurosci. February-2018;1(1):3-4.

6. Hedya SA, Avula A, Swoboda HD. Lithium Toxicity. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499992/