Lithium is a mood-stabilizing medication prescribed to patients with bipolar disorder. Lithium is considered the first-line therapy for bipolar disorder, as it works to reduce the severity and frequency of manic episodes. In addition, this mood stabilizer also treats and prevents depressive episodes in bipolar disorder.  

Lithium's exact mechanism of action is very complex. It is unknown how exactly this mood stabilizer works. However, it is believed that lithium helps to restore balanced levels of neurotransmitters (brain chemicals) in the central nervous system. Specifically, lithium affects the levels of serotonin, norepinephrine, epinephrine, and dopamine.  

Just as with other medications, lithium can cause various side effects. Some of the common side effects include increased thirst and urination, hand tremors, dry mouth, nausea, vomiting, vision change, and coordination problems. 

However, besides these common side effects, lithium toxicity can potentially occur with high blood lithium levels. This is due to lithium being a narrow therapeutic index (NTI) drug, meaning its toxic side effects can arise in the dosing range that is close to a therapeutic dose range. 

Therefore, it’s important to monitor lithium levels and signs of lithium toxicity to avoid excess lithium in the blood. Lithium toxicity occurs when there is too much lithium in the body, leading to serious health complications. Please continue reading to learn more about lithium toxicity, symptoms to look out for, and when to promptly medical care.   

What is lithium toxicity?

When you take too much lithium, the levels of lithium in the bloodstream become dangerously high, leading to a condition known as lithium toxicity or lithium poisoning. Lithium toxicity can lead to a range of symptoms and other potentially life-threatening complications. 

Types of lithium toxicity

There are three main types of lithium toxicity:

Acute lithium toxicity

Acute toxicity is when a person experiences sudden elevated levels of lithium due to a lithium overdose. This also can happen when you are severely dehydrated. Symptoms of acute lithium toxicity include nausea, vomiting, diarrhea, and abdominal pain. These symptoms typically take place within one hour of elevated lithium levels. Following gastrointestinal symptoms are neurological symptoms such as confusion, dizziness, muscle weakness, distorted speech, tremors, and, in severe cases, even coma or death. 

Chronic lithium toxicity

Long-term use of lithium causes chronic lithium toxicity. It develops gradually over time from high doses, improper monitoring, or renal toxicity, causing kidney impairment.

Hand tremors, increased thirst and urination (polyuria), weight gain, thyroid and kidney problems, and neurological issues are symptoms of chronic lithium intoxication. 

Acute-on-chronic toxicity

When someone experiences sudden worsening of symptoms with an existing history of chronic lithium toxicity, it is characterized by acute-on-chronic toxicity. It happens due to additional risk factors like dehydration, illness, or a medication interaction.

In this case, severe symptoms are observed, such as confusion, seizures, or cardiac problems. 

Therapeutic index of lithium

The therapeutic index of a medication is also known as the therapeutic window. It helps to determine the maximum toxic dose and minimum effective dose. Lithium has a narrow therapeutic index (NTI), meaning there is a very small difference between a toxic and therapeutic dose. In other words, when someone is taking lithium, a small increase in the amount taken can lead to lithium toxicity. On the other hand, a slight decrease in dosage can cause lithium treatment failure, leading to the health condition not being well-managed. 

Signs and symptoms of lithium toxicity

The severity and symptoms of lithium intoxication depend on how much lithium is being taken and the lithium levels in your blood. The signs and symptoms are divided according to the severity.

Mild lithium toxicity

Symptoms include:

• Increased hand tremors

• Nausea

• Diarrhea

• Upset stomach

• Shakiness

Moderate lithium toxicity

The signs and symptoms of moderate lithium toxicity include:

• Worsening lithium-induced tremor 

• Persistent nausea and vomiting

• Diarrhea

• Muscle weakness 

• Dizziness or lightheadedness

Severe lithium toxicity

Severe toxicity requires prompt medical attention due to its life-threatening symptoms.

Severe lithium toxicity symptoms include:

• Extreme confusion, delirium

• Low blood pressure

• Seizures

• Loss of consciousness

• Uncontrollable eye movements

• Slurred speech

• Rapid heartbeat

• Kidney failure

Other symptoms of lithium toxicity 

• Neurological Symptoms: Neurological symptoms of lithium toxicity are hand tremors, muscle twitching, seizures, confusion, slurred speech, and impaired coordination

• Gastrointestinal Symptoms: Intestinal symptoms include nausea, vomiting, and diarrhea, leading to dehydration and electrolyte imbalances. 

• Impaired Urinary Concentrating Ability: Increased urine production and excessive thirst indicate reduced kidney function.

• Mild Confusion: Mild confusion can be an early sign of lithium toxicity. Patients may have difficulty with thinking, focusing, or processing information.

Diagnosis of lithium toxicity

Serum levels

Blood work for testing serum levels is the primary method used to diagnose lithium toxicity. Results from blood tests help healthcare providers determine if blood lithium levels are within the therapeutic range or if there is too much lithium present.

Normal serum lithium levels

The normal serum lithium level range is  0.6 to 1.2 milliequivalents per liter (mEq/L) in adults. When the lithium level gets to 1.5 mEq/L or higher, lithium toxicity can occur.

Thyroid Stimulating Hormone (TSH) levels

Lithium can affect TSH levels and may lead to hyperthyroidism (the overproduction of thyroid hormone.) Therefore, healthcare providers can test TSH levels to diagnose lithium toxicity.  

Renal function assessment

Lithium excretion is primarily dependent on the kidneys. Evaluating kidney function is important to assess the kidneys' capability to eliminate lithium from the body.

Prevalence and management strategies

Prevalence of lithium toxicity is generally rare if the medication is taken exactly as prescribed in addition to appropriate monitoring. 

Lithium toxicity management strategies include:

• Gastric Lavage: Gastric lavage (stomach pumping) is a process to remove unabsorbed lithium from the stomach. It may be performed in cases of acute-on-chronic lithium toxicity.

• Bowel Irrigation: A solution is flushed into the gastrointestinal tract to remove any remains of lithium tablets or contents. 

• Lithium Carbonate Tablet: Activated charcoal or similar agents are administered to stop further absorption of lithium. Activated charcoal binds to lithium and flushes it as it is from the stomach to avoid absorbing it in the body.  

• Whole Bowel Irrigation: This procedure involves flushing the entire gastrointestinal tract with a special solution.

• Other medications: Chronic lithium treatment is sometimes treated with medications, such as sodium bicarbonate, to counteract the effects of lithium toxicity.

• Intensive Care Unit (ICU): Severe toxicity may require ICU admission to monitor vital signs closely, such as electrolyte levels, renal insufficiency, cardiac arrhythmias, seizures, and blood pressure.

How to prevent lithium poisoning?

You can prevent and avoid lithium toxicity through the following methods:

Follow instructions on the lithium prescription

Do not take more or less of the medication than prescribed by your doctor. Take lithium exactly as prescribed to help minimize the risk of lithium toxicity. Adjusting the dosage and intake without the input of your doctor is dangerous. 

Monitor lithium levels

Serum lithium levels must be monitored regularly to ensure that doses are adjusted as needed to manage therapeutic levels of lithium in the blood. Your doctor will determine how often you should get blood work done to check your lithium level. Lab work may need to be done more frequently if you are at increased risk for kidney injury and kidney failure. Risk factors include being elderly, being dehydrated, and taking other medications that can potentially cause kidney injury.

Dietary considerations

Taking lithium can cause sodium depletion. Eating a low-sodium diet can put you at an increased risk of lithium toxicity, especially at the beginning of therapy. You should be mindful before making any sudden dietary changes. Talk to your doctor and dietitian if you have questions or concerns about your sodium intake. 

References

• https://www.drugs.com/lithium.html

• https://www.ncbi.nlm.nih.gov/books/NBK499992/

• https://emedicine.medscape.com/article/815523-clinical

• https://www.ncbi.nlm.nih.gov/books/NBK519062/#:~:text=Monitoring%20of%20therapeutic%20levels%20includes,mEq%2FL%20for%20chronic%20therapy. 

• https://www.ncbi.nlm.nih.gov/books/NBK499992/#:~:text=Moderate%20intoxication%3A%20confusion%2C%20agitation%2C,%5B33%5D%20%5B34%5D. 

• https://emedicine.medscape.com/article/815523-workup 

• https://emedicine.medscape.com/article/815523-treatment#:~:text=Supportive%20therapy%20is%20the%20mainstay,benzodiazepines%2C%20phenobarbital%2C%20or%20propofol.