Brand names: Eskalith, Lithobid
Drug class: Antimanic Agents
VA class: CN750
CAS number: 554-13-2

Medically reviewed by Drugs.com on May 22, 2023. Written by ASHP.

Introduction

Antimanic agent.

Uses for Lithium

Bipolar Disorder

Management of bipolar disorder, particularly acute manic or mixed episodes in patients with bipolar 1 or bipolar 2 disorder.

A first-line agent in the initial treatment of depressive, manic, or mixed episodes in patients with bipolar disorder.

Combination therapy with an atypical antipsychotic, another mood stabilizing agent, and/or antidepressant may be required to adequately treat rapid cycling and more severe depressive, manic, or mixed episodes.

Maintenance therapy has been shown to prevent or diminish the intensity of subsequent manic episodes in patients with bipolar disorder with a history of mania.

Major Depression† [off-label]

Should be used only in patients who fail to respond to other antidepressants.

Schizoaffective and Schizophrenic Disorders† [off-label]

Limited effectiveness when used alone; should be used only after antipsychotic agents have failed.

May be added to existing antipsychotic therapy, but efficacy of such combined therapy has varied in different clinical studies. Careful monitoring (e.g., serum lithium concentrations, adverse effects, possible adverse drug interactions) recommended.

Disorders of Impulse Control† [off-label]

Has reduced temper outbursts, impulsive antisocial behavior, and the number of assaultive acts in a small number of adults with disorders of impulse control^{† [off-label]}.

Psychiatric Disorders in Children† [off-label]

Treatment of children with apparent mixed bipolar disorder symptomatology^†, hyperactivity with psychotic or neurotic components^†, or aggressive behavior^† or aggressive outbursts^† associated with attention-deficit hyperactivity disorder (ADHD); should be used only after more conservative therapies have failed.

Neutropenia and Anemia†

Treatment of neutropenia^† or anemia^† secondary to antineoplastic drugs.

Routine use not recommended for congenital, idiopathic, or cyclic neutropenias^†; Felty’s syndrome^†; or aplastic anemia^†.

Hyperthyroidism†

Treatment of hyperthyroidism^†; other treatments (e.g., radioactive iodine, surgery, propylthiouracil, methimazole) currently are preferred.

SIADH†

No longer considered one of the therapies of choice; generally has been replaced with other more effective and/or less toxic therapies (e.g., demeclocycline).

Lithium Dosage and Administration

General

• Careful monitoring of serum lithium concentrations and clinical status of the patient is mandatory and patients should be carefully instructed in the safe use of the drug.

• Carefully review the precautions and contraindications associated with lithium use before initiating therapy.

• Monitor serum lithium concentrations twice weekly during initiation of the acute phase of therapy and until serum concentration and clinical condition have stabilized; patient’s ability to tolerate high serum lithium concentrations usually decreases as initial manic symptoms begin to subside.

• After the patient has been stabilized, monitor serum concentrations at least every 2 months in most patients.

• Onset of acute antimanic effect of lithium usually occurs within 5–7 days; full therapeutic effect often requires 10–21 days.

• The manufacturers suggest that steady-state serum lithium concentrations be determined immediately before the next dose (i.e., 8–12 hours after the previous lithium dose). Total reliance must not be placed on serum lithium concentrations alone; accurate patient evaluation requires both careful clinical and laboratory evaluation.

• Serum lithium concentrations of 1–1.2 mEq/L usually are required during acute affective episodes. Serum concentration should not exceed 1.5 mEq/L during the acute treatment phase.

• If manifestations of lithium toxicity occur (see Lithium Toxicity under Cautions), temporarily discontinue for 24–48 hours, then resume at a lower dosage.

Administration

Oral Administration

Administer orally, preferably with meals in divided doses.

Administer conventional tablets, capsules, or oral solution 3 or 4 times daily; twice daily administration may be associated with adverse GI or nervous system effects. Administer extended-release tablets 2 or 3 times daily.

Extended-release preparations should be swallowed intact and should not be chewed, crushed, or halved.

Lithium citrate oral solutions may be useful in patients unable to swallow capsules or tablets; 5 mL of a commercially available solution contains about 8 mEq of lithium and is approximately equivalent to 300 mg of lithium carbonate.

Dosage

Available as lithium carbonate and lithium citrate; dosages expressed in terms of the salts.

Pediatric Patients

Bipolar Disorder

Acute Episodes†

Oral

Children ≤11 years of age: Usual dosages not established; lithium carbonate dosages of 15–20 mg/kg (about 0.4–0.5 mEq/kg) daily or equivalent lithium citrate dosages have been given in 2 or 3 divided doses. (Do not exceed usual adult dosages. )

Children ≥12 years of age: Dosages usually are the same as those of adults.

Maintenance Dosages†

Oral

Usual maintenance dosages have not been established; dosage should be adjusted according to serum lithium concentrations, patient tolerance, and clinical response.

Adults

Bipolar Disorder

Acute Episodes

Oral

Initially, 1.8 g daily as conventional lithium carbonate capsules or tablets, given in 3 or 4 divided doses, or 30 mL (about 48 mEq of lithium) of lithium citrate oral solution daily, given in 3 divided doses.

Alternatively, 900 mg twice daily (morning and evening) or 600 mg 3 times daily as extended-release lithium carbonate tablets.

Maintenance Dosages

Oral

900 mg to 1.2 g daily as conventional lithium carbonate capsules or tablets, given in 3 or 4 divided doses, or 15–20 mL (about 24–32 mEq of lithium) of lithium citrate oral solution daily, given in 3 or 4 divided doses. This dosage generally provides serum lithium concentrations of 0.6–1.2 mEq/L.

Alternatively, 900 mg to 1.2 g daily as extended-release lithium carbonate tablets, given in 2 or 3 divided doses.

Prescribing Limits

Pediatric Patients

Bipolar Disorder

Oral

When calculating dosage based on weight, do not exceed usual adult dosage.

Adults

Bipolar Disorder

Oral

Maintenance dosage usually should not exceed 2.4 g of lithium carbonate (65 mEq) daily.

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. Lower initial dosages (e.g., ≤900 mg of lithium carbonate daily) and more gradual dosage titration recommended.

May have decreased renal function; monitor renal function and adjust dosage accordingly.

Dosages that produce serum lithium concentrations at the lower end of therapeutic range may be sufficient for maintenance. (See Geriatric Use under Cautions.)

Pregnant Women

Dosages generally need to be increased during pregnancy but should be reduced 1 week before parturition or when labor begins. (See Fetal/Neonatal Morbidity and Mortality and also see Pregnancy under Cautions.)

Cautions for Lithium

Contraindications

• Significant renal or cardiovascular disease, severe debilitation, dehydration, sodium depletion, or concomitant therapy with diuretics; very high risk of lithium toxicity under such conditions.

• Only begin lithium in such patients if psychiatric indication is life-threatening, and other treatments have failed; however, must use with extreme caution, including daily serum lithium determinations and adjustment to usually low doses ordinarily tolerated by these individuals. In such instances, hospitalization is a necessity.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal toxicity (e.g., increase in cardiac and other anomalies, especially Ebstein’s anomaly) when administered to pregnant women, but potential benefits may be acceptable in certain conditions despite the possible risks to the fetus.

If used in women of childbearing potential, during pregnancy, or if a patient becomes pregnant during treatment, the patient should be be informed of the potential hazard to the fetus.

Whenever possible, lithium should be withdrawn for at least the first trimester unless it is determined that this would seriously endanger the mother. (See Pregnant Women under Dosage and Administration and see Pregnancy under Cautions.)

Lithium Toxicity

Risk of toxicity increases with increasing serum lithium concentrations. Serum concentration should not exceed 1.5 mEq/L during the acute treatment phase.

Serum lithium concentrations >1.5 mEq/L usually carry a greater risk than lower levels. (See General under Dosage and Administration.)

Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium concentrations <2 mEq/L. At higher levels, giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine may be seen.

Serum lithium levels above 3 mEq/L may produce a complex clinical picture involving multiple organs and organ systems. (See General under Dosage and Administration.)

Renal Effects

Diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia, possible following chronic lithium therapy. Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy also possible.

Measurement of 24-hour Cl_cr, renal-concentrating ability, and a urinalysis recommended prior to initiating therapy. Renal function should then be evaluated every 2–3 months for the first 6 months, then every 6–12 months during therapy or whenever clinically indicated.

If progressive or sudden changes in renal function, even within the normal range, occur during lithium therapy, reevaluate need for therapy with the drug.

Interactions

Encephalopathic syndrome reported with concomitant use with antipsychotic agents. May be similar to or same as neuroleptic malignant syndrome (NMS). (See Specific Drugs under Interactions.)

May prolong effects of neuromuscular blocking agents. (See Specific Drugs under Interactions.)

General Precautions

Concomitant Illnesses

Decreased tolerance to lithium has been reported to ensue from protracted sweating, diarrhea, or concomitant infection with elevated temperatures and may necessitate a temporary reduction or cessation of medication. Patients should maintain their usual fluid (2.5–3 L/day) and sodium intake, and supplement these in the event of fever (e.g., during infections), vomiting, or diarrhea.

Sodium-restricted Diet

Use with caution in patients whose sodium intake is restricted; stabilize sodium intake and carefully titrate lithium dosage to avoid increased serum lithium concentrations that may occur with sodium depletion.

Endocrine Effects

Hypothyroidism, with manifestations ranging from mild to severe myxedema, may occur within weeks to years after initiating lithium therapy; rarely, hypothyroidism may persist after discontinuance of the drug. Geriatric patients and patients with antithyroglobulin antibody, a prior history of Graves’ disease or Hashimoto’s thyroiditis, or those receiving iodine appear most at risk. Paradoxically, a few cases of hyperthyroidism also have been reported.

Preexisting thyroid disorders are not contraindications to lithium therapy. Patients with underlying hypothyroidism should have thyroid function (T₃, T₄, and TSH concentrations) evaluated yearly and be given supplemental thyroid therapy when needed.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Women of childbearing age receiving lithium should be counseled about methods of birth control. If used during pregnancy, carefully monitor serum lithium concentrations and adjust dosage accordingly. (See Pregnant Women under Dosage and Administration.)

Lactation

Lithium is distributed into milk; discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Pediatric Use

Safety and efficacy have not been established in children <12 years of age; however, the drug has been used in this age group when benefits were thought to outweigh risks.

Transient acute dystonia and hyperreflexia occurred in a 15-kg child who ingested 300 mg of lithium carbonate.

Geriatric Use

Insufficient experience with extended-release tablets in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.

Age-related differences in response to lithium generally not observed.

Use with caution; geriatric patients appear more susceptible to adverse effects (e.g., adverse nervous system and neuromuscular effects), even at therapeutic serum concentrations, and more prone to developing lithium-induced goiter and clinical hypothyroidism. Some clinicians recommend that thyroid function tests be performed every 6–12 months in these patients.

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy; geriatric patients should receive initial lithium dosages in the lower end of the usual range (see Geriatric Patients under Dosage and Administration).

Lithium is substantially excreted by the kidneys; consider monitoring renal function and adjust dosage if necessary since geriatric patients are more likely to have decreased renal function.

Common Adverse Effects

Fine hand tremor, polyuria, mild thirst, transient and mild nausea, and general discomfort may appear during the first few days of lithium administration; usually subside with continued treatment, a temporary reduction of dosage, or temporary cessation. If persistent, a cessation of therapy is indicated.

Drug Interactions

Lithium is not metabolized.

Electroconvulsive Therapy

Acute neurotoxicity with prominent delirium has occurred in patients receiving lithium and electroconvulsive therapy (ECT) concurrently. Some clinicians recommend decreasing lithium dosage or withdrawing the drug 2 days prior to ECT.

Specific Drugs

Lithium Pharmacokinetics

Absorption

Bioavailability

Conventional lithium carbonate capsules and tablets are 95–100% absorbed.

Extended-release lithium carbonate tablets are 60–90% absorbed.

Lithium citrate oral solutions are essentially 100% absorbed.

Onset

Acute antimanic effect usually occurs within 5–7 days; full therapeutic effect often requires 10–21 days.

Food

Food does not appear to affect the bioavailability of lithium.

Plasma Concentrations

Therapeutic serum lithium concentrations usually range from 1–1.2 mEq/L during acute affective episodes.

A 12-hour steady-state serum lithium concentration is used by most clinicians for monitoring serum concentrations; this concentration shows a high intraindividual (but not interindividual) reproducibility. (See General under Dosage and Administration.)

Distribution

Extent

Widely distributed into most body tissues and fluids, including bone, brain tissue, erythrocytes, saliva, and thyroid.

Lithium freely crosses the placenta; maternal and fetal serum concentrations are approximately equal. The milk of nursing women contains lithium concentrations that are approximately 33–50% of those in serum.

Plasma Protein Binding

Lithium is not bound to plasma proteins.

Elimination

Metabolism

Lithium is not metabolized.

Elimination Route

Principally renal.

Half-life

Approximately 24 hours.

Special Populations

In geriatric patients and patients with impaired renal function, serum half-lives of 36 and 40–50 hours, respectively, have been reported.

Clearance and distribution into erythrocytes may be increased during pregnancy. Immediately postpartum, renal clearance of lithium may decrease to pre-pregnancy levels.

Lithium is readily removed by hemodialysis but not as readily removed by peritoneal dialysis. Rebound increases in serum lithium concentration frequently occur 5–8 hours after dialysis.

Stability

Storage

Oral

Capsules, Tablets, and Extended-release Tablets

Well-closed containers at 15–30°C. Protect from moisture.

Solution

Tight containers at 15–30°C.

Actions

• Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown.

• Decreases renal-concentrating ability and water reabsorption and initially increases sodium and potassium excretion. Some of these effects are overcome by counteracting physiologic mechanisms, while others may persist. GFR may be slightly decreased in patients receiving prolonged lithium therapy.

• Various effects on the thyroid gland; principal effect is to block the release of thyroxine (T₄) and triiodothyronine (T₃) mediated by thyrotropin. This results in a decrease in circulating T₄ and T₃ concentrations and a feedback increase in serum thyrotropin concentration. Lithium also inhibits thyrotropin-stimulated adenylate cyclase activity and thyrotropin-induced release of thyroidal iodine 131, decreases intrathyroidal iodothyronine-iodotyrosine ratios, and inhibits colloid droplet formation.

Advice to Patients

• Importance of avoiding dehydration and maintaining usual sodium and fluid intake; importance of reporting polyuria and any prolonged vomiting, diarrhea, or fever to clinician.

• Importance of immediately discontinuing lithium therapy and consulting a clinician if signs of lithium intoxication (e.g., muscle twitching, tremor, mild ataxia, drowsiness, muscle weakness, diarrhea, vomiting) occur.

• Importance of advising patients that lithium may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• What is a proper diet to go on with lithium?

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