Lithium toxicity, also known as lithium overdose, is the condition of having too much

lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid ...

. Symptoms may include a tremor, increased reflexes, trouble walking, kidney problems, and an

altered level of consciousness An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousn ...

. Some symptoms may last for a year after levels return to normal. Complications may include

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include h ...

. Lithium toxicity can occur due to excessive intake or decreased excretion. Excessive intake may be either a

suicide attempt A suicide attempt is an attempt to die by suicide that results in survival. It may be referred to as a "failed" or "unsuccessful" suicide attempt, though these terms are discouraged by mental health professionals for implying that a suicide resu ...

or accidental. Decreased excretion may occur as a result of

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mi ...

such as from

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...

, a

low sodium diet A low sodium diet is a diet that includes no more than 1,500 to 2,400 mg of sodium per day. The human minimum requirement for sodium in the diet is about 500 mg per day, which is typically less than one-sixth as much as many diets "season ...

, or from

kidney problems Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. The diagnosis is generally based on symptoms and supported by a lithium level of greater than 1.2 mEq/L.

Gastric lavage Gastric lavage, also commonly called stomach pumping or gastric irrigation, is the process of cleaning out the contents of the stomach. Since its first recorded use in early 19th century, it has become one of the most routine means of eliminating ...

and

whole bowel irrigation Whole bowel irrigation (WBI) is a medical process involving the rapid administration of large volumes of an osmotically balanced macrogol solution (GoLYTELY, CoLyte), either orally or via a nasogastric tube, to flush out the entire gastrointesti ...

may be useful if done early.

Activated charcoal "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an inter ...

is not effective. For severe toxicity

hemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...

is recommended. The risk of death is generally low. Acute toxicity generally has better outcomes than chronic toxicity. In the United States about 5,000 cases are reported to

poison control center A poison control center is a medical service that is able to provide immediate, free, and expert treatment advice and assistance over the telephone in case of exposure to poisonous or hazardous substances. Poison control centers answer questions ...

s a year. Lithium toxicity was first described in 1898.

Signs and symptoms

Symptoms of lithium toxicity can be mild, moderate, or severe. Mild symptoms include nausea, feeling tired, and tremor occur at a level of 1.5 to 2.5 mEq/L. Moderate symptoms include confusion, an increased heart rate, and low muscle tone occur at a level of 2.5 to 3.5 mEq/L. Severe symptoms include coma, seizures, low blood pressure and increased body temperature which occur at a lithium concentration greater than 3.5 mEq/L. When lithium overdoses produce neurological deficits or cardiac toxicity, the symptoms are considered serious and can be fatal.Watkins, J. B., Klaassen, C. D., & Casarett, L. J. (2010). ''Casarett & Doulls essentials of toxicology''. Place of publication not identified: McGraw Hill Medical.

Acute toxicity

In acute toxicity, people have primarily gastrointestinal symptoms such as

and

, which may result in

volume depletion Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the loss ...

. During acute toxicity, lithium distributes later into the central nervous system causing dizziness and other mild neurological symptoms.

Chronic toxicity

In chronic toxicity, people have primarily neurological symptoms which include

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, f ...

hyperreflexia Hyperreflexia is overactive or overresponsive bodily reflexes. Examples of this include twitching and spastic tendencies, which indicate upper disease of the upper motor neurons and the lessening or loss of control ordinarily exerted by highe ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of t ...

, and change in mental status. During chronic toxicity, the gastrointestinal symptoms seen in acute toxicity are less prominent. The symptoms are often vague and nonspecific.

Acute on chronic toxicity

In acute on chronic toxicity, people have symptoms of both acute and chronic toxicity.

Complications

People who survive an intoxication episode may develop persistent health problems. This group of persistent health symptoms are called syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). The syndrome presents with irreversible neurological and neuro-psychiatric effects. The neurological signs are

cerebellar The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebe ...

dysfunction,

extrapyramidal symptoms Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

, and

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is ...

dysfunction. The neuro-psychiatric findings present with memory deficits, cognitive deficits, and sub-cortical dementia. For a diagnosis, the syndrome requires the absence of prior symptoms and persistence of symptoms for greater than 2 months after cessation of lithium.

Pathophysiology

Lithium is readily absorbed from the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...

. It is distributed to the body with higher levels in the kidney,

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The t ...

, and bone as compared to other tissues. Since lithium is almost exclusively excreted by the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

s, people with preexisting

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, ...

are at high risk of developing lithium intoxication. The drug itself is also known to be

nephrotoxic Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxin ...

, opening up the possibility of spontaneous emergence of toxicity at doses that were previously well-tolerated. Lithium toxicity can be mistaken for other syndromes associated with antipsychotic use, such as

because lithium increases serotonin metabolites in the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

. There are several drug interactions with lithium. Interactions can occur from

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics m ...

s or

atypical antipsychotics The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and n ...

. In particular, certain drugs enhance lithium levels by increasing renal re-absorption at the proximal tubule. These drugs are

angiotensin-converting enzyme inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume ...

non-steroidal anti-inflammatory drugs Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

and

thiazide diuretics Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first ...

Diagnosis

The diagnosis is generally based on symptoms and supported by a lithium level blood level. Blood levels are most useful six to twelve hours after the last dose. The normal serum lithium level in those on treatment is between 0.6-1.2 mEq/L. Some blood tubes contain lithium heparin which may result in falsely positive results. When lithium toxicity is suspected tests may include: * fingerstick glucose * serum lithium concentration *

basic metabolic panel A basic metabolic panel (BMP) is a blood test consisting of a set of seven or eight biochemical tests and is one of the most common lab tests ordered by health care providers. Outside the United States, blood tests made up of the majority of the ...

to assess renal function * serum

acetaminophen Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferio ...

and

salicylate Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substanc ...

concentrations to rule out other sources of acute ingestion * urine pregnancy tests to ensure management does not cause

abortion Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregn ...

Imaging tests are not helpful.

Treatment

If the person's lithium toxicity is mild or moderate, lithium dosage is reduced or stopped entirely. If the toxicity is severe, lithium may need to be removed from the body. The removal of lithium is done in a hospital emergency department. It may involve: *

. A tube is placed through the nose or mouth into the stomach. The tube is used to remove lithium that has not been digested yet. It may also be used to put medicines directly into the stomach to help stop lithium from being absorbed. * Use of an artificial kidney to clean the blood (''dialysis''). This is usually done only in the most severe cases. *Diuretic medications such as

furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mout ...

and hydration via intravenous

normal saline Saline (also known as saline solution) is a mixture of sodium chloride (salt) and water. It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses, and help with dry eyes. By injection into a vein i ...

appear to be effective in speeding the removal of lithium and also rehydrate patients who've lost fluids. *Hemodialysis. Hemodialysis is widely advocated as a means of reducing the risk of permanent neurological sequelae following lithium poisoning. Although hemodialysis clearly enhances the elimination of lithium, it is unclear whether this translates into improved patient outcomes. People may be sent home once their lithium level is less than 1.5 mEq/L and they have no symptoms.

References

{{Elements in biology Biology and pharmacology of chemical elements Bipolar disorder Depression (mood) Element toxicology Lithium Lithium in biology Mood disorders Toxic effects of metals Toxicology Wikipedia medicine articles ready to translate