Lithium is a naturally occurring element that is classified as an anti-manic drug. It is available in the United States under the brand names Eskalith, Lithonate, Lithane, Lithotabs, and Lithobid. It is also sold under its generic name.
Lithium is commonly used to treat mania and bipolar depression (manic depression). Less commonly, lithium is used to treat certain mood disorders, such as schizoaffective disorder and aggressive behavior and emotional instability in adults and children. Rarely is lithium taken to treat depression in the absence of mania. When this is the case, it is usually taken in addition to other antidepressant medications.
Lithium salts have been used in medical practice for about 150 years. Lithium salts were first used to treat gout. It was noted in the 1880s that lithium was somewhat effective in the treatment of depression, and in the 1950s lithium was seen to improve the symptoms of bipolar disease (manic depression). The way lithium works in the body is unclear, but its therapeutic benefits are probably related to its effects on other electrolytes such as sodium, potassium, magnesium, and calcium. Lithium is taken either as lithium carbonate tablets or capsules or as lithium citrate syrup.
The therapeutic effects of lithium may appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. People taking lithium should be aware of this and continue taking the drug as directed even if they do not see immediate changes in mood.
Lithium is available in 300-mg tablets and capsules, 300-mg and 450-mg sustained-release tablets, and a syrup containing approximately 300 mg per teaspoonful.
Depending on the patient’s medical needs, age, weight, and kidney function, doses of lithium can range from 600 to 2,400 mg per day, although most patients will be stabilized on 600 to 1,200 mg per day. Patients who require large amounts of lithium often benefit from the addition of another anti-manic drug, which may allow the dose of lithium to be lowered.
Generally, lithium is taken two or three times daily. However, the entire dose may be taken at once if the physician believes that a single daily-dose program will increase patient compliance. The single-dose schedule is especially helpful for people who are forgetful and may skip doses on a multiple-dose schedule. Additionally, evidence indicates that once-daily doses are associated with fewer side effects.
More than with any other drugs used in the treatment of mental disorders, it is essential to maintain lithium blood levels within a certain narrow range to derive the maximum therapeutic benefit while minimizing serious negative side effects. It is important that patients have their blood levels of lithium measured at regular intervals.
Because lithium intoxication may be serious and even life-threatening, blood concentrations of lithium should be measured weekly during the first four weeks of therapy and less often after that.
Patients taking lithium should have their thyroid function monitored and maintain an adequate sodium (salt) and water balance. Lithium should not be used or used only with very close physician supervision in patients with kidney impairment, heart disease, and other conditions that affect sodium balance. Dosage reduction or complete discontinuation may be necessary during infection, diarrhea, vomiting, or prolonged fast. Patients who are pregnant, breast-feeding, those over age 60, and people taking diuretics (“water” pills) should discuss the risks and benefits of lithium treatment with their doctors before beginning therapy. Lithium should be discontinued 24 hours before a major surgery, but may be continued normally for minor surgical procedures.
Tremor is the most common neurological side effect. Lithium tremor is an irregular, nonrhythmic twitching of the arms and legs that is variable in both intensity and frequency. Lithium-induced tremors occur in approximately half of people taking this medication. The chance of tremors decreases if the dose is reduced. Acute lithium toxicity (poisoning) can result in neurological side effects, ranging from confusion and coordination impairment, to coma, seizures , and death. Other neurological side effects associated with lithium therapy include lethargy, memory impairment, difficulty finding words, and loss of creativity.
About 30 to 35% of patients experience excessive thirst and urination, usually due to the inability of the kidneys to retain water and sodium. However, lithium is not known to cause kidney damage.
Lithium inhibits the synthesis of thyroid hormone. About 10 to 20% of patients treated with lithium develop some degree of thyroid insufficiency, but they usually do not require supplementation with thyroid hormone tablets.
Gastrointestinal side effects include loss of appetite, nausea, vomiting, diarrhea, and stomach pain. Weight gain is another common side effect for patients receiving long-term treatment. Changes in saliva flow and enlargement of the salivary glands may occur. An increase in tooth cavities and the need for dental care among patients taking lithium has been reported.
Skin reactions to lithium are common but can usually be managed without discontinuing lithium therapy. Lithium may worsen folliculitis (inflammation of hair follicles), psoriasis, and acne. Thinning of the hair may occur, and, less commonly, hair loss may be experienced. Swollen feet are an uncommon side effect that responds to dose reduction.
Electrocardiographic abnormalities may occur with lithium therapy, but significant cardiovascular effects are uncommon except as the result of deliberate or accidental overdose.
A mild-to-moderate increase in the number of white blood cells is a frequent side effect of lithium use. Conversely, lithium may slow the formation of red blood cells and cause anemia.
Increased risk of fetal cardiovascular disease may be associated with the use of lithium during pregnancy, especially during the first trimester (first three
Bipolar disease —A mental disorder characterized by periods of mania alternating with periods of depression.
Compliance —In medicine or psychiatry, cooperation with a treatment plan or schedule of medications.
Electrocardiograph (EKG) —A test that measuresthe electrical activity of the heart as it beats. An abnormal EKG can indicate possible cardiac disease.
Mania —An elevated or euphoric mood or irritable state that is characteristic of bipolar I disorder. This state is characterized by mental and physical hyper-activity, disorganization of behavior, and inappropriate elevation of mood.
Schizoaffective disorder —A mental disorder that shows a combination of symptoms of mania and schizophrenia.
Thyroid —A gland in the neck that produces the hormone thyroxine, which is responsible for regulating metabolic activity in the body. Supplemental synthetic thyroid hormone is available as pills taken daily when the thyroid fails to produce enough hormone.
months). For this reason, pregnant women should discontinue lithium use until the second or third trimester and should receive alternative treatments for their mania.
Patients taking lithium should always be concerned that other medications they are taking may adversely interact with it; patients should consult their physician or pharmacists about these interactions. The following list represents just some of the medications that lithium may interact with to either (a) increase or decrease the effectiveness of the lithium or (b) increase or decrease the effectiveness of the other drug:
- angiotensin converting enzyme inhibitors such as captopril, lisinopril, or enalapril
- nonsteroidal anti-inflammatory drugs such as ibuprofen or naprosyn
- diuretics (water pills) such as hydrochlorothiazide, furosemide, or ethacrynic acid
- asthma drugs such as theophylline and aminophylline
- anticonvulsants such as phenytoin and carbamazepine
- calcium channel blockers such as verapamil or diltiazem
- muscle relaxants such as methocarbamol, carisoprodol, and cyclobenzaprine
- metronidazole, a commonly prescribed antibiotic used to treat infections
- antidiabetic therapy
- amiodarone, an antiarrhythmic drug
- antacids containing sodium bicarbonate
American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.
Preston, John D., John H. O’Neal, and Mary C. Talaga. Handbook of Clinical Psychopharmacology for Therapists. 4th ed. Oakland, CA: New Harbinger Publications, 2004.
Baldessarini, Ross J., Maurizio Pompili, and Leonardo Tondo. “Suicide in Bipolar Disorder: Risks and Management.” CNS Spectrums 11.6 (June 2006): 465–71.
Baldessarini, Ross J., and others. “Decreased Risk of Suicides and Attempts During Long-Term Lithium Treatment: A Meta-Analytic Review.” Bipolar Disorders 8.5, part 2 (Oct. 2006): 625–39.
De Fruyt, Jürgen, and Koen Demyttenaere. “Bipolar (Spectrum) Disorder and Mood Stabilization: Standing at the Crossroads?” Psychotherapy and Psychosomatics 76.2 (Jan. 2007): 77–88.
El-Mallakh, Rif, and others. “Bipolar II Disorder: Current and Future Treatment Options.” Annals of Clinical Psychiatry 18.4 (Oct.-Dec). 2006: 259–66.
Eyer, Florian, and others. “Lithium Poisoning: Pharmacokinetics and Clearance During Different Therapeutic Measures.” Journal of Clinical Psychopharmacology 26.3 (June 2006): 325–30.
Gonzalez-Pinto, Ana, and others. “Suicidal Risk in Bipolar I Disorder Patients and Adherence to Long-Term Lithium Treatment.” Bipolar Disorders 8.5, part 2 (Oct. 2006): 618–24.
Kellner, Charles H., and others. “Continuation Electroconvulsive Therapy vs Pharmacotherapy for Relapse Prevention in Major Depression.” Archives of General Psychiatry 63.12 (Dec. 2006): 1337–44.
Livingstone, Callum, and Hagen Rampes. “Lithium: A Review of Its Metabolic Adverse Effects.” Journal of Psychopharmacology 20.3 (May 2006): 347–55.
McElroy, Susan L., and others. “Antidepressants and Suicidal Behavior in Bipolar Disorder.” Bipolar Disorders 8.5, part 2 (Oct. 2006): 596–617.
Ozcan, Mehmet Erkan, Geetha Shivakumar, and Trisha Suppes. “Treating Rapid Cycling Bipolar Disorder with Novel Medications.” Current Psychiatry Reviews 2.3 (Aug. 2006): 361–69.
Patel, Nick C., and others. “Lithium Treatment Effects on Myo-Inositol in Adolescents with Bipolar Depression.” Biological Psychiatry 60.9 (Nov. 2006): 998-1004.
Singh, Jaskaran B., and Carlos A. Zarate, Jr. “Pharmacological Treatment of Psychiatric Comorbidity in Bipolar Disorder: A Review of Controlled Trials.” Bipolar Disorders 8.6 (Dec. 2006): 696–709.
Jack H. Raber, Pharm.D.
Ruth A. Wienclaw, PhD