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Lithium

Forms

  • Tablet: 300mg (slow release); 450mg (controlled release)
  • Capsule: 150mg, 300mg, 600mg
  • Liquid 8mEq/5ml

Uses of Lithium

Lithium is very commonly used for treating Bipolar Disorder, and can help to relieve Manic, Hypomanic, Depressive and Mixed Episodes.

It is also used to treat episodes of Major Depressive Disorder, usually after other standard medications for Depression have been tried and have not worked completely.

How Lithium Works

Lithium is considered a Mood Stabilizer. Its mechanisms of action are diverse and remain incompletely understood. It alters sodium transport across nerve and muscle cells, alters intracellular signaling via second-messenger systems, and alters the metabolism of neurotransmitters including catecholamines and serotonin.

Cautions when Using Lithium

In people with kidney disease or cardiovascular disease, advice from the appropriate medical specialist should be obtained before starting Lithium (see serious side-effects).

Lithium overdoses can be potentially life-threatening (see Lithium Toxicity)

Lithium can reach toxic levels in people who are dehydrated. Being in hot climates, exercising, or having diarrhea are common causes of dehydration. Lithium use itself can lead to dehydration by inducing frequent urination and diarrhea. It is thus important to be drinking lots of fluids when using Lithium and to make sure that one's urine does not become dark yellow, which is a sign of being dehydrated.

Women in childbearing years should consider taking contraceptives while using Lithium, given the risk of pregnancy complications.

Dosing of Lithium

Lithium doses are determined based on blood serum concentrations. Serum levels should be measured 5 days after starting Lithium or 5 days after any dose change, and blood samples should always be drawn 12 hours after the last dose.

For acute Manic, Hypomanic, Depressive or Mixed Episodes, the target serum concentration is between 0.8 and 1.1 mmol/L. For maintenance treatment (preventing future episodes once the previous episode has resolved), the target is between 0.6 and 0.9 mmol/L.

The usual starting dose is 300mg two or three times a day. It is then adjusted upwards as indicated by serum levels. Higher doses can also be given two or three times daily. Doses should not exceed serum levels of 1.2mmol/L due to risk of toxicity.

When wanting to stop Lithium, the dose should be reduced very gradually over a period of about 12 weeks. In the treatment of Bipolar Disorder, stopping Lithium abruptly should be avoided as this can lead to a relapse in the short term [ref] and increased suicidality [ref].

Onset of action

It usually takes about 1 to 3 weeks for Lithium to have a clinical effect.

Kidney impairment

Lithium serum levels should be monitored carefully. Not recommended in cases of severe kidney impairment.

Liver impairment

No dose change necessary.

Side-effects of Lithium

Below is a list of most of the reported side-effects of Lithium. Most of these side-effects occur in only a minority of individuals taking Lithium, and many also resolve with time while Lithium is continued. If side-effects occur that are not tolerable, then the first step should be to lower the Lithium dose (except in the case of serious side-effects, where the Lithium should be stopped). With proper medical monitoring Lithium is a safe and effective treatment.

Cardiovascular: arrhythmias (see serious side-effects); bradycardia; ankle and wrist swelling; low blood pressure.

Central Nervous System: tremor (often noticeable in the hands, best to avoid caffeine if this occurs); sedation (try lowering daytime dose); cognitive dulling (includes memory problems, feeling mentally slowed, or feeling emotionally numbĀ and apathetic); headache; unsteadiness (can be a sign of Lithium toxicity); slurred speech (can be a sign of Lithium toxicity).

Dermatologic: rash; worsening of psoriasis; acne; hair thinning and loss; dry skin.

Endocrine: hypothyroidism (if this occurs, it can be corrected with Synthroid, and there should be no need to stop the Lithium); hyperparathyroidism and hypercalcemia.

Eyes, Ears, Nose and Throat: blurred vision; dry mouth; ear ringing; parotitis; taste distortion.

Gastrointestinal: weight gain (can be substantial, and may or may not be associated with increased appetite); nausea; vomiting; abdominal pains; diarrhea.

Genitourinary: polyuria (urinating excessively) and polydipsia (feeling thirsty) (this occurs commonly and is not concerning so long as renal functions remain normal); urinary urgency; renal impairment (see serious side-effects); impotence/ sexual dysfunction (rare and not permanent).

Hematologic: leukocytosis (increased levels of white blood cells).

Muskulosceletal: muscular weakness.

Common side-effects of Lithium

Nausea, abdominal pains, fatigue, weight gain, hand tremors, frequent urination, mental slowing, hypothyroidism (can be corrected with Synthroid).

Rare but serious side-effects of Lithium

  • Kidney problems: More likely with long-term Lithium use, and can include glomerulonephritis, nephrogenic diabetes insipidus, and kidney failure.  These problems are prevented by measuring renal functions every few months (see below) and discontinuing Lithium if early signs of renal impairment are found.
  • Cardiac arrythmias: Includes T-wave flattening and inversion, bradycardia, and sick sinus syndrome. Regular medical monitoring should pick-up any of these changes before they become severe.
  • Intracranial hypertension (pseudotumor cerebri): This is exceedingly rare.
  • Seizures: This is very rare, and usually occurs in the context of Lithium toxicity.

Lithium toxicity

When Lithium reaches high concentrations in the body it can give rise to a toxicity syndrome, which includes:

Coarse tremor, slurred speech, unsteadiness, lethargy, confusion, nausea, vomiting, polyuria, myoclonus, seizures, and delirium. If not treated, this can lead to coma and death.

Lithium toxicity is a medical emergency, and individuals who show signs of this syndrome will need to stop their Lithium immediately and to be brought to the hospital for medical monitoring and stabilization.

Lithium toxicity is usually associated with serum concentrations above 1.5 mmol/L. However, this cut-off level is not absolute, and Lithium toxicity can occur when serum levels are normal or even low [ref]. This is because intracellular Lithium concentrations in neurons can become elevated even when blood serum levels appear normal. This can be detected by measuring intracellular red blood cell Lithium levels, though many hospitals will not be equipped to perform this test. As a result, Lithium toxicity remains a clinical diagnosis and should be suspected whenever patients show the above symptoms.

Lithium and pregnancy

Lithium can lead to serious cardiac malformations of the fetus, including Epstein's anomaly, in 0.1% of cases, which is 20 times the risk in the general population.  This risk is highest when Lithium used in 1st trimester.  In 4-12% of cases, there can be polyhydramnios, premature delivery, floppy baby syndrome, thyroid abnormalities, and diabetes insipidus.

Treating sexual side-effects of Lithium in men

Sexual side-effects, including erectile difficulties, are rare, but can occur. One study found that using Aspirin 240mg daily can alleviate these side-effects in men [ref].

Medical Monitoring for Lithium

Before starting Lithium, and then every six months, the following laboratory tests should be performed in order to monitor for the development of serious side-effects:

  • Renal function tests, including serum creatinine to calculate eGFR, and urinalysis to assess specific gravity and proteinuria [ref].
  • Electrolytes
  • Calcium levels (to monitor for hyperparathyroidism and renal impairment)
  • Thyroid function tests, including TSH, T3, and T4
  • Complete Blood Count (to monitor for leukocytosis)
  • Electrocardiogram in individuals above age 50 (to monitor for cardiac arrhythmias)
  • Consider pregnancy tests

Drug Interactions with Lithium

Substances that can increase Lithium levels include:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) like Aspirin and Ibuprofen
  • Thiazide diuretics
  • Potassium-sparing diuretics (Spironolactone)
  • ACE-inhibitors
  • Loop diuretics (Furosemide)

Substances that can lower Lithium levels include:

  • Osmotic diuretics
  • Xanthines/ theophyllines (including Caffeine)
  • Carbonic anhydrase inhibitors (Acetazolamide)