Version July 2025
Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy.
Dosing guidance:
Safety: Only prescribe in settings where serum concentration monitoring is available. Toxic effects occur with serum concentrations ≥1.5 mEq/L and may be seen in some patients with serum concentrations as low as 1.2 mEq/L (Ref).
Dosing: All doses in this monograph are expressed as the equivalent amounts of lithium carbonate salt. Initial dosing frequency varies by formulation; however, if initial dose is ≤300 mg/day, may initiate as once daily regardless of formulation (Ref).
Dosage form information: Lithium citrate 5 mL (8 mEq) oral solution is equivalent to carbonate 300 mg tablets/capsules.
Bipolar disorder (monotherapy or combination therapy):
Acute mania, acute episodes with mixed features (labeled use), acute hypomania (off-label use), or acute bipolar major depression (alternative agent; off-label use): For most patients, a therapeutic response occurs with serum concentrations between 0.8 and 1.2 mEq/L; some respond to lower levels (eg, 0.6 mEq/L). For treatment of acute severe mania, typically given in combination with an antipsychotic or antiseizure drug (Ref).
Oral: Immediate release or extended release: Initial: 600 to 900 mg/day in 2 to 3 divided doses based on chosen formulation (initially administer IR daily dose in 2 to 3 divided doses and ER daily dose in 2 divided doses); increase based on response and tolerability by 300 to 600 mg every 1 to 5 days to usual therapeutic dose range of 900 mg/day to 1.8 g/day in 1 to 3 divided doses based on tolerability or chosen formulation. After 5 to 7 days at a stable therapeutic dose, further adjust as needed based on clinical response, tolerability, and serum concentration (Ref). Note: After several weeks at an established dose and stable serum concentrations, may consolidate schedule to a single dose of immediate release or extended release at bedtime (Ref).
Maintenance treatment to prevent manic or depressed episodes: Note: Continue regimen (ie, monotherapy or combination) that was used to achieve control of the acute episode; a lower dose and serum concentration at the lower end of the therapeutic range may suffice for some patients (Ref).
Cluster headache, prevention (off-label) (alternative agent):
Note: Use in patients who do not tolerate preferred preventative agent (Ref). For most patients, a therapeutic response occurs with serum concentrations between 0.6 and 0.8 mEq/L; level should not exceed 1.2 mEq/L (Ref).
Oral: Immediate release or extended release: Initial: 300 to 400 mg once daily; after 4 to 5 days, adjust dose based on serum concentrations (eg, 400 mg twice daily); increase up to 1.5 g/day if needed based on response, tolerability, and serum concentrations. Initially administer IR, then may administer maintenance daily dose with IR in 2 to 4 divided doses or ER in 1 or 2 divided doses (Ref).
Major depressive disorder, unipolar (alternative agent; adjunctive therapy) (off-label use): For most patients, a therapeutic response occurs with serum concentrations between 0.6 and 1.2 mEq/L; some respond to lower serum concentrations (Ref). Peak clinical improvement may take up to 6 weeks when lithium is used for antidepressant augmentation for acute depression (Ref).
Oral: Immediate release or extended release: Initial: 300 to 600 mg/day in 1 to 2 divided doses; if initial dose is ≤300 mg/day, may initiate as once daily regardless of formulation (Ref); may increase based on response and tolerability every 1 to 5 days to a target dose of 600 mg to 1.2 g/day in 1 to 3 divided doses based on tolerability or chosen formulation (administer IR daily dose in 2 to 3 divided doses and ER daily dose in 2 divided doses (Ref)). Note: After several weeks at an established dose and stable serum concentrations, may consolidate schedule to a single dose of immediate release or extended release at bedtime (Ref).
Postpartum psychosis (off-label use):
Note: Administer as combination therapy with an antipsychotic (Ref). Consider the addition of an antidepressant for patients with prominent depressive symptoms and lithium monotherapy in patients with mild levels of disorganization (Ref).
Oral: Initial: 300 mg once daily; may increase to 300 mg twice daily on day 2. After 5 days, may further adjust as needed based on clinical response, tolerability, and serum concentration. Continue treatment for ≥1 year (Ref).
Dosing conversion: To convert between IR and ER capsules/tablets, administer the same total daily dose. Initially administer IR daily dose in 2 to 3 divided doses and ER daily dose in 2 divided doses. If initial dose is ≤300 mg/day, may initiate as once daily regardless of formulation (Ref). After several weeks at an established dose, may consolidate schedule to a single dose of immediate release or extended release at bedtime (Ref). When taken as a single dose per day, serum trough concentrations are 10% to 26% higher compared to serum trough concentrations with divided doses, due to changes in renal excretion (Ref). Individual dosage adjustments may be necessary.
Discontinuation of therapy: Gradual dose reduction is advised to avoid disease recurrence unless discontinuation is due to significant adverse effects. If it is necessary to switch to a different drug during acute treatment, decrease the lithium dose over 1 to 2 weeks (eg, by 300 mg each day or every other day) (Ref). In order to detect disease recurrence when discontinuing maintenance treatment for bipolar disorder, decrease lithium over several weeks to months when feasible (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS
Note: Lithium is primarily excreted via the kidneys and clearance correlates directly with glomerular filtration rate (Ref). Because of the risk of lithium-related nephrotoxicity, routine monitoring of serum lithium levels and kidney function are recommended in patients with reduced kidney function (Ref).
Altered kidney function: Oral:
CrCl ≥60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 30 to <60 mL/minute: Initiate at low doses (eg, 150 to 300 mg/day) in 1 to 2 divided doses, titrate slowly based on clinical response and tolerability, monitor levels frequently (Ref).
CrCl <30 mL/minute: Avoid use (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral: No data available. Consider dose adjustments based on serum lithium levels (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (up to 80% removed from extracellular fluid; however, lithium remains in tissue and significant increases in lithium concentration [also known as "rebound"] occur as lithium equilibrates from tissue compartments into the blood stream) (Ref); lithium levels drawn immediately post hemodialysis will be inaccurate/falsely low:
Oral: Avoid use when possible. Consider use of an alternative therapy, especially in patients with significant residual kidney function due to risk of lithium-induced kidney damage. If necessary, initiate therapy at 300 mg 3 times weekly after dialysis; gradually titrate based on clinical response, tolerability, and serum lithium levels (Ref). In some patients, daily dosing may be required to achieve targeted lithium serum levels (Ref).
Peritoneal dialysis: Dialyzable (less than hemodialysis) (Ref):
Oral: Avoid use when possible. Consider use of an alternative therapy, especially in patients with significant residual kidney function due to risk of lithium-induced kidney damage. If necessary, start at low dose (eg, 150 mg daily); gradually titrate based on clinical response, tolerability, and serum lithium levels (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
Oral: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
Oral: Avoid use (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling.
Bipolar disorder: Initiate therapy with lower doses; refer to adult dosing. Some guidelines recommend lower target serum concentrations (eg, 0.4 to 0.8 mEq/L for older adults) (Ref).
(For additional information see "Lithium: Pediatric drug information")
Dosage guidance:
Dosage form information: Each 5 mL of lithium citrate oral solution contains 8 mEq of lithium ion, equivalent to the amount of lithium in 300 mg of lithium carbonate immediate-release capsules/tablets. Lithium oral solution has been discontinued in the United States for >1 year.
Bipolar disorder: Note: Monitor serum concentrations and clinical response (efficacy and toxicity) to determine proper dose. For acute therapy of pediatric bipolar disorder (acute manic/mixed episodes without psychosis), lithium has been suggested as augmentation therapy with a second-generation antipsychotic (SGA) (due to decreased suicidality) or as monotherapy if a trial of two different SGAs lacks adequate response (Ref).
Immediate release: Children ≥7 years and Adolescents: Limited data available in weight <20 kg: Note: Dosing in weight <20 kg extrapolated from clinical experience (Ref).
Lithium carbonate capsule or tablet:
Patient weight <30 kg: Oral: Initial: 300 mg twice daily, increase dose at weekly intervals in 300 mg/day increments as tolerated to clinical response and goals based on type of therapy (acute or maintenance).
Acute therapy: Oral: Titrate dose to 600 to 1,500 mg/day in divided doses and target serum lithium concentration of 0.8 to 1.2 mEq/L; a maximum dose is not described in the manufacturer labeling; in trials, weight-dependent maximum daily doses were reported: Patients <23 kg: 900 mg/day; patients ≥23 kg: 40 mg/kg/day and doses were not further increased if serum lithium concentration was ≥1.4 mEq/L. In a multicenter, double-blind, placebo-controlled efficacy trial for treatment of acute mania, the mean effective daily dose was 956 ± 225 mg/day. For all patients in the trial (regardless of weight) the mean final dose was: 30.5 ± 8.7 mg/kg/day (Ref).
Maintenance therapy: Oral: Titrate dose to 600 to 1,200 mg/day in divided doses and target serum trough concentration of 0.8 to 1 mEq/L as tolerated.
Patient weight ≥30 kg: Oral: Initial: 300 mg 3 times daily, increase dose in 300 mg/day increments every 3 days as tolerated to clinical response and goals based on type of therapy (acute or maintenance).
Acute therapy: Oral: Titrate dose to 600 mg twice or 3 times daily and target serum lithium concentration of 0.8 to 1.2 mEq/L; a maximum dose is not described in the manufacturer labeling; in trials, reported doses did not exceed a maximum daily dose of 40 mg/kg/day and doses were not further increased if serum lithium concentration was ≥1.4 mEq/L. In a multicenter, double-blind, placebo-controlled efficacy trial for treatment of acute mania, the mean effective daily dose was 1,583 ± 524 mg/day. For all patients in the trial (regardless of weight) the mean final dose was 30.5 ± 8.7 mg/kg/day (Ref).
Maintenance therapy: Oral: Titrate dose to 300 to 600 mg twice or 3 times daily and target serum trough concentration of 0.8 to 1 mEq/L as tolerated; in a long-term trial, doses were not further increased if serum lithium concentration was ≥1.4 mEq/L (Ref).
Lithium citrate oral solution:
Patient weight <30 kg: Oral: Initial: 8 mEq twice daily, increase dose at weekly intervals in 8 mEq increments as tolerated to clinical response and goals based on type of therapy (acute or maintenance).
Acute therapy: Titrate dose to 16 to 40 mEq/day in divided doses and target serum lithium concentration of 0.8 to 1.2 mEq/L; a maximum dose is not described in the manufacturer labeling; in trials, weight-dependent maximum daily doses were reported: Patients <23 kg: 900 mg of lithium carbonate/day; patients ≥23 kg: 40 mg of lithium carbonate/kg/day and doses were not further increased if serum lithium concentration was ≥1.4 mEq/L (Ref).
Maintenance therapy: Oral: Titrate dose to 16 to 32 mEq/day in divided doses and target serum trough concentration of 0.8 to 1 mEq/L as tolerated and doses were not further increased if serum lithium concentration was ≥1.4 mEq/L (Ref).
Patient weight ≥30 kg: Oral: Initial: 8 mEq 3 times daily, increase dose in 8 mEq increments every 3 days as tolerated to clinical response and goals based on type of therapy (acute or maintenance).
Acute therapy: Oral: Titrate dose to 16 mEq twice or 3 times daily and target serum lithium concentration of 0.8 to 1.2 mEq/L; maximum doses are not described in the manufacturer labeling; in trials, reported doses did not exceed a maximum daily dose of: 40 mg of lithium carbonate/kg/day and doses were not further increased if serum lithium concentration was ≥1.4 mEq/L (Ref).
Maintenance therapy: Oral: Titrate dose to 8 to 16 mEq twice or 3 times daily and target serum trough concentration of 0.8 to 1 mEq/L as tolerated; in a long-term trial, doses were not further increased if serum lithium concentration was ≥1.4 mEq/L (Ref).
Extended release: Children ≥12 years and Adolescents: Oral: Weight-based usual daily dosing administered in 2 divided doses: <22 kg: 600 mg/day; 22 to 41 kg: 900 mg/day, and >41 kg: 1,200 mg/day (Ref). In an open-label trial of 27 subjects (age range: 12 to 18 years), an initial dose of 15 mg/kg/dose twice daily, maximum initial dose: 600 mg/dose, with dose titration at weekly intervals as tolerated to target serum lithium concentration of 1 to 1.2 mEq/L was used (Ref). In adults, therapy is initiated at a low dose (eg, 450 mg 2 times daily or less); increased gradually based on response and tolerability (Ref); the usual adult dosage is 900 to 1,800 mg/day in 2 divided doses.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Immediate release: Children ≥7 years and Adolescents: Oral:
CrCl >89 mL/minute: No dosage adjustment required.
CrCl 30 to 89 mL/minute: Initiate therapy with low dose; titrate slowly with frequent monitoring.
CrCl <30 mL/minute: Avoid use.
Extended release: Children ≥12 years and Adolescents: Oral: There are no dosage adjustments provided in the manufacturer's labeling; monitor renal function closely during therapy and re-evaluate treatment with any changes in renal function.
There are no dosage adjustments provided in the manufacturer's labeling.
Lithium may cause cardiac arrhythmia, including bradycardia, sinoatrial dysfunction (SA block), abnormal T waves on ECG (T-wave inversion), and ST-segment depression (Ref). Additional cardiovascular affects have occurred, including peripheral edema, hypotension, and cardiovascular collapse (Ref). Brugada syndrome (Brugada ECG pattern) may be unmasked with lithium therapy (Ref). In a scientific statement from the American Heart Association, lithium has been determined to be an agent that may cause direct myocardial toxicity that is reversible upon discontinuation (magnitude: major) (Ref).
Mechanism: Serum concentration-related; affects various ion channels in the myocardium, in particular Na/K channels, and leads to decreased intracellular potassium levels. These changes alter the normal functioning of the myocardium, leading to conduction disturbances and ECG abnormalities (Ref).
Onset: Varied; may occur within days of initiation of medication, dose increase, or addition of interacting medication or be delayed (Ref).
Risk factors:
• Higher serum levels, particularly toxic levels (>1.5 mEq/L) (Ref)
• Concurrent medications that either inhibit the excretion of lithium via the kidneys or have additive effects on the myocardium (Ref)
• Kidney impairment (Ref)
• Brugada syndrome: Family history of Brugada syndrome, family history of sudden death at a young age (Ref)
Lithium may cause a variety of CNS effects in adult and pediatric patients including drowsiness, sedated state, ataxia, abnormal gait, confusion, decreased alertness, disorientation, lethargy, memory impairment, slurred speech, headache, and others (Ref) . More significant manifestations may occur with elevated serum lithium levels or toxicity, such as coma, seizure (including tonic-clonic twitching), hallucination, agitation, abnormal electroencephalogram (EEG), and may proceed to death without intervention (Ref). Of note, some patients may describe decreased creativity and cognitive dulling as an adverse reaction, when it could also be a result of effective treatment of their manic episode and resultant decreased manic symptoms. CNS effects may persist indefinitely during treatment. Tolerance may or may not occur over time (Ref). Cognitive adverse reactions may be a reason for medication nonadherence, but it is unclear whether these adverse reactions are associated with lithium or bipolar disorder (Ref).
Mechanism: Dose-related; may be related to neuronal cell membrane polarization/depolarization, alterations in glutamate functioning, increases in serotonin release, inhibition of inositol monophosphatase, and alteration of CNS catecholamine levels (Ref).
Onset: Varied; may begin soon after initiation. Effects may be exacerbated with dose increases (or increased serum levels) or intentional or unintentional overdoses (Ref).
Risk factors:
• Higher doses/serum levels (Ref)
• Concurrent use of medications reducing the clearance of lithium (eg, angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs, diuretics) (Ref)
• Concurrent use of other CNS depressant medications (eg, sedative-hypnotics, antipsychotics, antiseizure medications, etc.) (Ref)
• Older adults (Ref)
• Preexisting neurocognitive impairment (Ref)
• Current episode of depression (Ref)
Lithium may cause acne vulgaris and/or psoriasis (including exacerbation of acne and exacerbation of psoriasis) in patients with and without either condition at baseline. May vary from mild to severe, and occur on the face, scalp, trunk, and extremities (Ref). Plaque-type psoriasis is the most common presentation, but others may occur (Ref).
Mechanism: Dose-related; may exert toxic effects on the follicular epithelium, producing acne through neutrophilic chemotaxis and degranulation. In addition, the inflammatory cascade may become activated, leading to psoriasis. Follicular plugging may also contribute to these effects (Ref).
Onset: Varied; typically takes several months to develop, although exacerbations of existing acne or psoriasis may occur sooner (Ref).
Risk factors:
• Males (Ref)
• Preexisting moderate to severe psoriasis (Ref)
A variety of adverse GI effects have been reported with lithium in adult and pediatric patients, including dyspepsia, diarrhea, nausea, vomiting, dysgeusia (metallic or salty taste), gastritis, and abdominal pain (Ref). Some effects (eg, nausea) my subside over time. Vomiting is typically associated with toxicity (Ref). Supratherapeutic lithium concentrations should be suspected with severe nausea, vomiting, and diarrhea (Ref).
Mechanism: Dose-related; may be related to direct irritation on the stomach lining or related to other physiological processes in the body after absorption. Potential effects of increased serotonin release may play a role in nausea, as well as general electrolyte changes (Ref).
Onset: Varied; some effects (eg, nausea, diarrhea) may occur early in treatment. Other effects may take longer to develop (Ref).
Risk factors:
• Earlier in treatment (Ref)
• Higher doses/serum levels (Ref)
• Peak lithium levels (possible association) (Ref)
• Controlled-release preparations may be associated with less upper GI cramping and nausea, but increased diarrhea compared to immediate-release formulations (Ref)
Hypercalcemia has been reported with lithium treatment, which may or may not be related to drug-induced hyperparathyroidism. Symptoms may include weakness, fatigue, development of renal stones (calculi), osteoporosis, GI distress, and others. Psychiatric disturbances, including depression, may also develop, and potentially be misinterpreted as a new episode of the underlying mood disorder (Ref). Changes are usually reversible if lithium is discontinued; however, sustained hypercalcemia and parathyroid gland enlargement have been reported (Ref).
Mechanism: While unclear, lithium is thought to inhibit calcium receptors in the parathyroid gland, preventing inhibition of parathyroid hormone (PTH) release. As PTH levels rise, this alters calcium homeostasis leading to hypercalcemia (Ref).
Onset: Varied; while lithium has been observed to affect PTH levels after a single dose, more long-term exposure (ie, years) is likely required to observe clinically relevant alterations in calcium homeostasis. Progression to osteoporosis would likely take a significant exposure time as well (Ref).
Risk factors:
Exact risk factors unclear, but may include:
• Longer duration of treatment (Ref)
• Females (Ref)
Lithium treatment has been associated with various thyroid function abnormalities, but most commonly hypothyroidism in adult and pediatric patients (Ref). Patients may present with typical hypothyroidism signs and symptoms, including lethargy, impaired cognition, weight gain, dry skin, and cold intolerance. Additionally, depressive symptoms may worsen/emerge and be misinterpreted as a component of the underlying mood disorder (Ref).
Mechanism: While unclear, it is thought that lithium has varied effects on thyroid hormone production and regulation, including inhibition of iodine uptake in the thyroid, inhibition of thyroid hormone synthesis and release, and hepatic conversion of free thyroxine (Ref).
Onset: Hypothyroid features, either symptomatic or lab-value based, generally occur after years of lithium treatment. While acute changes have been noted within the first month of treatment, it is much more likely after several years of use (Ref).
Risk factors:
• Females (Ref)
• Older adults (Ref)
• Family history of hypothyroidism (Ref)
• Presence of antithyroid antibodies (Ref)
Lithium is classified as a narrow-therapeutic index drug, requiring close monitoring to ensure patients’ serum levels are maintained within the therapeutic range. Supratherapeutic levels, even slight elevations above 1.5 mEq/L, may lead to increased adverse reactions and toxicity. Notably, toxicity can occur at any level (Ref). General symptoms of low-grade lithium toxicity may include weakness, tremor (new-onset or worsening), mild ataxia, poor concentration, tinnitus, nausea, and diarrhea. More significant toxicity may result in vomiting, gross/coarse tremor, slurred speech, confusion, nystagmus disorder, dysarthria, and lethargy. If not treated, it may lead to seizure (tonic-clonic), coma, neurological damage, and death (Ref). Permanent neurotoxicity, described as the syndrome of irreversible lithium-effectuated neurotoxicity (SILENT), has been reported with acute and chronic lithium toxicity (Ref).
Mechanism: Lithium toxicity is an augmented presentation of the various adverse reactions seen with treatment (Ref).
Onset: Varied; may occur within minutes of ingestion (mostly GI effects), but more significant symptoms may take over an hour or more to manifest. There are also reports of delayed symptom onset several days after ingestion (Ref).
Risk factors:
• Higher doses/serum levels (Ref)
• Concurrent use of drugs or medications (eg, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists) that increase serum levels (Ref)
• Acute alterations in serum electrolytes or dehydration (Ref)
• Older adults (may manifest symptoms at lower comparative serum levels) (Ref)
• Kidney impairment (Ref)
Nephrogenic diabetes insipidus may occur (Ref). The ability of the kidney to retain free water may become impaired, leading to dehydration and electrolyte disturbances, most notably hypernatremia. Additionally, serum lithium levels may increase due to the decreased dilutional effect from decreased whole body water. Symptoms of nephrogenic diabetes insipidus and its related hypernatremia may include polyuria, polydipsia, lethargy, and irritability. More severe cases may progress to muscle twitching, coma, seizures, and death. Nephrogenic diabetes insipidus may persist after prolonged lithium therapy despite discontinuation (Ref).
Mechanism: Dose- and duration-related. Lithium-related changes in the collecting tubules of the kidney decrease sensitivity to antidiuretic hormone, leading to decreased concentrating ability and increased production of dilute urine. Lithium may reduce aquaporin-2 water channels within the collecting duct, causing reduction of water reabsorption (Ref). As total body stores of free water decrease, the sensation of thirst increases to compensate (Ref).
Onset: Varied; typical onset within 2 to 4 months of initiation but may occur earlier or later (Ref).
Risk factors:
• Longer duration of treatment (Ref)
• Higher doses/serum levels (Ref)
• Any episodes of lithium toxicity (Ref)
• Extended release or multiple-daily dose regimens (Ref)
• Nonresponse to lithium (may be a risk factor) (Ref)
• Infection (Ref)
• Dehydration (Ref)
• Alcohol intoxication (Ref)
Common adverse reactions associated with lithium are polyuria and polydipsia. These reactions may vary in intensity from mild to more significant effects on overall quality of life. Patients may notice increased urinary frequency (>3 L in 24 hours) due to poor urine concentration. As a result of decreased body water stores, patients may also report increased thirst, which is independent of any dry mouth effects of the drug. May decrease in intensity over time in some patients as the kidneys compensate for this effect (Ref). Refer to "nephrogenic diabetes insipidus" for long-term complications.
Mechanism: Lithium-related changes in the collecting tubules of the kidney decrease sensitivity to antidiuretic hormone, leading to decreased concentrating ability and increased production of dilute urine. As total body stores of free water are decreased, the sensation of thirst increases to compensate (Ref).
Onset: Varied; may occur early in treatment (within days) or later in treatment (Ref).
Risk factors:
• Longer duration of treatment (Ref)
• Higher doses/serum levels episodes (Ref)
• Any episodes of lithium toxicity (Ref)
• Concurrent use of other psychotropic medications, especially antipsychotics (Ref)
• Multiple-daily dose regimens (conflicting data) (Ref)
Up to one-third of patients may develop some degree of decreased kidney function over the course of lithium treatment, with a smaller percentage (~5%) developing significant kidney impairment/failure (eGFR <30 mL/minute). Changes in eGFR (decreased creatinine clearance), renal concentrating defect, and other parameters have been observed in these patients. The development of polyuria/polydipsia may or may not be an early marker for later development of kidney insufficiency. Progression of kidney impairment may continue after discontinuation of lithium in some patients (Ref). Chronic kidney disease will develop in 17% to 21% of long-term users (Ref).
Mechanism: Duration-related; related to various changes in kidney morphology, including interstitial nephritis and fibrosis, nephron atrophy, and possibly glomerular damage. Hypothesized to be related to acute decreases in kidney sensitivity to antidiuretic hormone, causing gradual change in kidney function over time (Ref). Time from lithium initiation to progression to chronic kidney disease and end stage renal disease is 16.5 to 31 years, and 23 years, respectively (Ref).
Onset: Typically delayed, although acute changes may occur with acute toxicity. As lithium exposure continues over years, the rate of more significant kidney impairment increases as the alternations in kidney structure become more severe (Ref).
Risk factors:
• Longer duration of treatment (Ref)
• Older adults (Ref)
• Any episodes of lithium toxicity (Ref)
• Higher doses/serum concentrations (probable risk factor) (Ref)
• Concurrent use of other psychotropic medications, especially antipsychotics (Ref)
Various types of sexual dysfunction have been reported with lithium treatment, in both females and males. While the rates of the various effects are not clear (anywhere from <5% to nearly 40% in studies), they may include decreased libido, impaired sexual arousal, erectile dysfunction, and general decreased sexual satisfaction. Negative effects on orgasm are unclear. Sexual dysfunction can negatively impact patients’ quality of life (Ref).
Mechanism: Exact mechanism is unclear. Effects on promoting serotonin release may play a role, similar to the serotonin-augmenting effects of antidepressants (Ref).
Onset: Varied; may take days to weeks or longer (Ref).
Risk factors:
No clear risk factors have been described. Possible risk factors include:
• Concurrent use of benzodiazepines (Ref)
• Concurrent use of other medications that cause sexual dysfunction (eg, antidepressants) (probable risk factor) (Ref)
Lithium may cause tremor in nearly one-quarter of patients, making it one of the most common adverse reactions. Most commonly seen as a bilateral, symmetrical hand tremor, similar to essential tremor; although, this may vary to other limbs and in symmetry (Ref). May spontaneously decrease over time as compensatory mechanisms develop within the patient (Ref). Coarse tremor and muscle twitching may be observed in lithium toxicity (Ref).
Mechanism: Exact mechanism is unclear; thought to be related to CNS depressant effects, leading to dysregulation of fine muscle control (Ref).
Onset: Varied; commonly begins early in treatment but can develop later in treatment (with or without a dose increase) (Ref).
Risk factors:
• Higher doses/serum levels (Ref)
• Concurrent use of medications reducing the clearance of lithium (eg, angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs, diuretics) (Ref)
• Concurrent use of other medications known to induce tremor (eg, antipsychotics, antidepressants) (Ref)
• Concurrent use of caffeine (Ref)
• Concurrent anxiety disorder (Ref)
• Personal or family history of essential tremor (Ref)
• Older adults (Ref)
• Concurrent substance withdrawal (especially alcohol) (Ref)
Weight gain is reported as one of the more common and bothersome adverse reactions of lithium. May include weight gain of 10 kg or more over time with an average increase in body weight of 6 kg (Ref). This can lead to other medical comorbidities and negative effects on mood and adherence to treatment (Ref). Many pediatric studies suggest that lithium has a low risk for weight gain (not statistically different than placebo), with many demonstrating that it is weight neutral (Ref).
Mechanism: Exact mechanism is unclear. Effects on central mechanisms related to weight gain, satiety, and metabolism are possible. In addition, increased consumption of high-calorie, sugary beverages from increased thirst due to lithium could play a role, as well as any drug-induced hypothyroidism and fluid retention (Ref).
Onset: Varied; may occur within the first few weeks of initiation, with more significant increases over time. Increases of 4 to 7 kg within the first year have been reported in the literature. While the most significant weight gain typically occurs within the first 1 to 2 years of treatment, it may continue (Ref).
Risk factors:
Unclear, but may include:
• Concurrent use of other medications that can cause weight gain (particularly other psychotropic medications) (Ref)
• Early weight gain after treatment initiation (Ref)
• Overweight/obese prior to initiation (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Abnormal T waves on ECG (including inversion T wave on ECG and flattened T wave of ECG), bradycardia (Ref), cardiac arrhythmia (including unmasking of Brugada Syndrome) (Ref), chest tightness, circulatory shock, cold extremities, edema, hypotension, myxedema (Ref), peripheral vascular disease (resembling Raynaud’s syndrome), prolonged QT interval on ECG, sinus node dysfunction, syncope, ventricular tachyarrhythmia
Dermatologic: Acne vulgaris (Ref), alopecia, dermal ulcer, dermatitis, dry and/or thinning hair, exacerbation of acne (Ref), exacerbation of psoriasis, folliculitis, pruritus, psoriasis, skin rash, xeroderma
Endocrine & metabolic: Albuminuria, dehydration, diabetes insipidus, euthyroid goiter, glycosuria, hypercalcemia (including secondary to hyperparathyroidism (Ref)), hyperglycemia, hypermagnesemia, hyperparathyroidism, hyperthyroidism, hyponatremia, weight loss
Gastrointestinal: Abdominal pain, anorexia, decreased appetite, dental caries, dysgeusia (including metallic taste and salty taste), dyspepsia, fecal incontinence, flatulence, gastritis, salivary gland disease (swelling), sialorrhea, swelling of lips, tongue changes (movement), vomiting, xerostomia
Genitourinary: Glomerulopathy (fibrosis), impotence, nephron atrophy, nephrotic syndrome (Ref), oliguria, sexual disorder, urinary incontinence
Hematologic & oncologic: Leukocytosis
Hypersensitivity: Angioedema
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Ref)
Local: Local pain (fingers and toes), local skin discoloration (fingers and toes), localized edema (ankles and wrists)
Nervous system: Abnormal electroencephalogram (diffuse slowing, potentiation, disorganization of background rhythm), abnormal gait, ataxia, bradyphrenia, cogwheel rigidity, coma, confusion, decreased mental acuity (worsening of organic brain syndromes), disorientation, dizziness, drowsiness, dystonic reaction, epileptiform seizure, extrapyramidal reaction, fatigue, hallucination, headache, hyperactive behavior (startled response), hyperactive deep tendon reflex, hyperirritability (muscle), hypertonia, idiopathic intracranial hypertension, involuntary choreoathetoid movements, lethargy, local anesthesia (skin), memory impairment, myasthenia, psychomotor impairment, restlessness, sedated state, seizure, slurred speech, stupor, tic disorder, vertigo
Neuromuscular & skeletal: Arthralgia, joint swelling, polyarthralgia, tremor
Ophthalmic: Blurred vision, exophthalmos, nystagmus disorder, transient scotoma
Otic: Tinnitus
Renal: Decreased creatinine clearance, interstitial nephritis, renal concentrating defect
Miscellaneous: Fever, interstitial fibrosis, iodism (elevated iodine uptake)
Postmarketing:
Endocrine & metabolic: Hypothyroidism (common: ≥10%) (Ref), nephrogenic diabetes insipidus (common: ≥10%) (Ref), polydipsia (common in long-term patients: ≥10%) (Ref), weight gain (common: ≥10%) (Ref)
Gastrointestinal: Diarrhea (common: ≥10%) (Ref), nausea (common: ≥10%) (Ref)
Nervous system: Intracranial hypertension (Ref)
Neuromuscular & skeletal: Lupus-like syndrome (Ref)
Renal: Polyuria (common in long-term patients: ≥10%) (Ref)
Hypersensitivity to lithium or any component of the formulation.
Immediate-release capsule, solution and tablet: Severe cardiovascular or renal disease, severe debilitation, dehydration, sodium depletion, concurrent use with diuretics.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US manufacturer’s labeling): Brain damage; conditions requiring low sodium intake.
Concerns related to adverse effects:
• Pseudotumor cerebri: Pseudotumor cerebri (increased intracranial pressure and papilledema) has rarely been reported with use; undetected cases may result in blind spot enlargement, visual field constriction, and blindness secondary to optic atrophy. Discontinue therapy, if clinically possible, if syndrome occurs.
• Serotonin syndrome: Lithium can precipitate a potentially life-threatening serotonin syndrome, particularly when used in combination with other serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, tramadol, buspirone, St. John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, monoamine oxidase inhibitors). Monitor patients closely for signs of serotonin syndrome, such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise and initiate supportive therapy.
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. Case reports illustrate lithium toxicity after bariatric surgery, specifically Roux-en-Y gastric bypass and sleeve gastrectomy (Dahan 2019; Lin 2020; Musfeldt 2016). Use caution in patients receiving lithium therapy after bariatric surgery, and closely monitor postoperative lithium levels and for symptoms of lithium toxicity or consider changing to an alternative agent.
• Cardiovascular disease: Generally avoid use in patients with significant cardiovascular disease due to risk of precipitation of cardiac arrhythmia; if use is unavoidable, use with extreme caution and monitor serum lithium levels and EKG closely.
• Depression/suicidal ideation: Use with caution in patients at risk of suicide (suicidal thoughts or behavior) by drug overdose; lithium has a narrow therapeutic index (Nelson 2017).
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may exacerbate condition (Mehrizi 2012).
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as carbonate:
Generic: 150 mg, 300 mg, 600 mg
Solution, Oral, as citrate:
Generic: 8 mEq/5 mL (5 mL, 473 mL, 500 mL)
Tablet, Oral, as carbonate:
Generic: 300 mg
Tablet Extended Release, Oral, as carbonate:
Lithobid: 300 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
Generic: 300 mg, 450 mg
Yes
Capsules (Lithium Carbonate Oral)
150 mg (per each): $0.14 - $0.47
300 mg (per each): $0.17 - $1.71
600 mg (per each): $0.39 - $1.88
Solution (Lithium Oral)
8 mEq/5 mL (per mL): $2.85
Tablet, controlled release (Lithium Carbonate ER Oral)
300 mg (per each): $0.25 - $0.47
450 mg (per each): $0.46 - $0.54
Tablet, controlled release (Lithobid Oral)
300 mg (per each): $15.08
Tablets (Lithium Carbonate Oral)
300 mg (per each): $0.21 - $0.34
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as carbonate:
Carbolith: 150 mg, 300 mg [contains fd&c yellow #6 (sunset yellow)]
Carbolith: 600 mg [contains fd&c blue #1 (brilliant blue)]
Lithane: 150 mg, 300 mg
Generic: 150 mg, 300 mg, 600 mg
Tablet Extended Release, Oral, as carbonate:
Lithmax: 300 mg
Oral: Administer with meals to decrease GI upset. ER tablets must be swallowed whole; do not crush or chew.
Bariatric surgery: Lithium is available as an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery; providers should determine if the condition being treated can be safety monitored or if a switch to an alternative formulation or agent is necessary (Dvořáčková 2024). Lithium is also available in IR formulations.
Oral: Administer with meals to decrease GI upset. Do not crush or chew extended release dosage form; swallow whole.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Bipolar disorder:
Immediate release: Treatment of acute mania, acute episodes with mixed features, and maintenance treatment in patients ≥7 years of age with a diagnosis of bipolar disorder.
Extended release: Treatment of manic episodes and maintenance treatment in patients ≥12 years of age with a diagnosis of bipolar disorder.
Bipolar disorder, hypomania; Bipolar major depression; Cluster headache, prevention; Major depressive disorder, unipolar; Postpartum psychosis
Eskalith may be confused with Estratest.
Lithium may be confused with lanthanum, Ultram.
Lithobid may be confused with Levbid, Lithostat.
Lithium is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with QTc prolongation (O’Mahony 2023).
Do not confuse mEq (milliequivalent) with mg (milligram). Note: 300 mg lithium carbonate or citrate contain 8 mEq lithium. Dosage should be written in mg (milligrams) to avoid confusion.
Check prescriptions for unusually high volumes of the syrup for dosing errors.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Almotriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Alosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Amphetamines: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor
Angiotensin II Receptor Blockers: May increase serum concentration of Lithium. Management: Initiate lithium at lower doses in patients receiving an angiotensin II receptor blocker (ARB). Consider lithium dose reductions in patients stable on lithium therapy who are initiating an ARB. Monitor lithium concentrations closely when combined. Risk D: Consider Therapy Modification
Angiotensin-Converting Enzyme Inhibitors: May increase serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider Therapy Modification
Antiemetics (5HT3 Antagonists): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Antipsychotic Agents: Lithium may increase neurotoxic effects of Antipsychotic Agents. Lithium may decrease serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor
BusPIRone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Caffeine and Caffeine Containing Products: May decrease serum concentration of Lithium. Risk C: Monitor
Calcitonin: May decrease serum concentration of Lithium. Risk C: Monitor
Calcium Channel Blockers (Nondihydropyridine): May increase neurotoxic effects of Lithium. Calcium Channel Blockers (Nondihydropyridine) may increase serum concentration of Lithium. Decreased or unaltered lithium concentrations have also been reported with this combination. Risk C: Monitor
Calcium Polystyrene Sulfonate: May decrease serum concentration of Lithium. Management: To minimize the risk for interaction, separate dosing of oral CPS and lithium by administering lithium at least 3 hours before or at least 3 hours after CPS. Consider a 6 hour dose separation in patients with gastroparesis. Risk D: Consider Therapy Modification
CarBAMazepine: May increase adverse/toxic effects of Lithium. Risk C: Monitor
Carbonic Anhydrase Inhibitors: May decrease serum concentration of Lithium. Risk C: Monitor
Cardiac Glycosides: Lithium may increase adverse/toxic effects of Cardiac Glycosides. Risk C: Monitor
Cyclobenzaprine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Dapoxetine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid
Desmopressin: Lithium may decrease therapeutic effects of Desmopressin. Desmopressin may increase serum concentration of Lithium. Risk C: Monitor
Dexmethylphenidate-Methylphenidate: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Dextromethorphan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Eletriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Ergot Derivatives: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Fenfluramine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Fosphenytoin-Phenytoin: May increase adverse/toxic effects of Lithium. Risk C: Monitor
Gepirone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Lasmiditan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Levomethadone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Linezolid: May increase serotonergic effects of Lithium. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider Therapy Modification
Loop Diuretics: May decrease serum concentration of Lithium. Loop Diuretics may increase serum concentration of Lithium. Risk C: Monitor
Metaxalone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Methadone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Methyldopa: May increase adverse/toxic effects of Lithium. This may occur without notable changes in serum lithium concentrations. Risk C: Monitor
Methylene Blue: May increase serotonergic effects of Lithium. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider Therapy Modification
Metoclopramide: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
MetroNIDAZOLE (Systemic): May increase adverse/toxic effects of Lithium. MetroNIDAZOLE (Systemic) may increase serum concentration of Lithium. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): May increase serotonergic effects of Lithium. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider Therapy Modification
Monoamine Oxidase Inhibitors (Type B): May increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Risk X: Avoid
Nefazodone: May increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Neuromuscular-Blocking Agents: Lithium may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May increase serum concentration of Lithium. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May increase serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider Therapy Modification
Ondansetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists (metabolized by CYP3A4): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opipramol: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Ornidazole: May increase adverse/toxic effects of Lithium. Ornidazole may increase serum concentration of Lithium. Risk C: Monitor
Osmotic Diuretics: May decrease serum concentration of Lithium. Management: Consider temporarily discontinuing use of osmotic diuretics during coadministration with lithium. If coadministration is required, monitor lithium concentrations and for signs of lithium toxicity frequently. Risk D: Consider Therapy Modification
Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
OxyCODONE: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Potassium Iodate: Lithium may increase hypothyroid effects of Potassium Iodate. Risk C: Monitor
Potassium Iodide: May increase hypothyroid effects of Lithium. Risk C: Monitor
Potassium-Sparing Diuretics: May decrease serum concentration of Lithium. Potassium-Sparing Diuretics may increase serum concentration of Lithium. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Ramosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Sargramostim: May increase adverse/toxic effects of Lithium. Specifically, the myeloproliferative effects may be increased. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: Serotonergic Agents (High Risk, Miscellaneous) may increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonergic Non-Opioid CNS Depressants: Serotonergic Agents (High Risk, Miscellaneous) may increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonergic Opioids (High Risk): May increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor
Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Sertindole: Lithium may increase QTc-prolonging effects of Sertindole. Risk X: Avoid
Sodium Chloride: May increase excretion of Lithium. Risk C: Monitor
Sodium Polystyrene Sulfonate: May decrease serum concentration of Lithium. Management: To minimize the risk for interaction, separate dosing of oral sodium polystyrene sulfonate (SPS) and lithium by administering lithium at least 3 hours before or at least 3 hours after SPS. Consider a 6 hour dose separation in patients with gastroparesis. Risk D: Consider Therapy Modification
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May decrease serum concentration of Lithium. Risk C: Monitor
St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Syrian Rue: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Tetracyclines: May increase serum concentration of Lithium. Risk C: Monitor
Theophylline Derivatives: May decrease serum concentration of Lithium. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: May decrease excretion of Lithium. Management: Reduce the lithium dose if coadministered with thiazide or thiazide-like diuretics. Monitor serum lithium levels during coadministration with thiazide and thiazide-like diuretics. Risk D: Consider Therapy Modification
Tilidine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Topiramate: May increase serum concentration of Lithium. Risk C: Monitor
Tricyclic Antidepressants: May increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Tryptophan: Lithium may increase serotonergic effects of Tryptophan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Valproic Acid and Derivatives: Lithium may increase serum concentration of Valproic Acid and Derivatives. Risk C: Monitor
Vasopressin: Drugs Suspected of Causing Diabetes Insipidus may decrease therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic hormone effects of vasopressin may be decreased. Risk C: Monitor
Ziprasidone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Preconception counseling is recommended prior to treating bipolar disorder (CANMAT/ISBD [Yatham 2018]). Establish effective lithium serum concentrations while symptomatically stabilized prior to conception (ACOG 2023). When medications are needed to treat bipolar disorder in patients planning to become pregnant, the lowest effective dose is recommended (CANMAT/ISBD [Yatham 2018]).
When treating depression, evaluate pregnancy status prior to initiating treatment in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of antidepressant response (ACOG 2023; WFSBP [Dodd 2018]). When treating depression, lithium is not a first line medication for use prior to conception in patients who are treatment naive or who do not have a history of effective treatment. Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]).
Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]).
Female fertility is not impaired with lithium use; sperm motility may be impaired (BAP [McAllister-Williams 2017]).
Lithium crosses the placenta; fetal concentrations are similar to those in the maternal plasma (Newport 2005).
Outcome data following maternal use of lithium during pregnancy are available (Cohen 2019; Fornaro 2020; Hastie 2021; Poels 2020; Poels 2021; Sagué-Vilavella 2022). Although cardiac malformations in the infant, including Ebstein anomaly, are associated with use of lithium during the first trimester of pregnancy, the absolute risk may be low (ACOG 2023; BAP [McAllister-Williams 2017]). Consider fetal echocardiography during the second trimester (between 16 and 20 weeks' gestation) if first–trimester exposure occurs (ACOG 2023). Lithium toxicity, including floppy baby syndrome associated with cardiac, hepatic, and neurologic abnormalities may occur following in utero exposure. Symptoms may include apnea, bradycardia, cyanosis, depressed neonatal reflexes, feeding difficulties, hypotonia, lethargy, and respiratory distress. Symptoms may take up to 14 days to resolve. Monitor and provide supportive care until toxicity resolves.
Data related to the long-term effects of in utero lithium exposure on infant neurodevelopment are limited (BAP [McAllister-Williams 2017]; Haskey 2017; Poels 2018).
Due to pregnancy-induced physiologic changes, lithium renal clearance is increased (Clark 2022; Molenaar 2021; Westin 2017). Hyperemesis or acute blood loss may also change lithium concentrations. Dose adjustments may be needed to maintain therapeutic response. Closely monitor serum concentrations to maintain levels within the therapeutic window (ACOG 2023). During pregnancy, once-daily doses may be divided and given twice daily to avoid high peak maternal plasma concentrations, which may then minimize fetal exposure (ACOG 2023; Wesseloo 2017). Guidelines suggest decreasing or discontinuing the lithium dose 24 to 48 hours prior to planned delivery or at the onset of labor to reduce the risk of maternal intoxication and decrease neonatal concentrations (ACOG 2023; BAP [McAllister-Williams 2017]). Following delivery, the lithium dose may be restarted at the preconception dose. Adjust postpartum doses based on maternal lithium trough concentrations (ACOG 2023).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated bipolar disorder is associated with fetal growth restriction, preterm birth, adverse neurodevelopment, and may increase the risk of postpartum psychosis. Discontinuing effective medications during pregnancy increases the risk of relapse. Management should be made as part of a shared decision-making process (ACOG 2023).
Patients effectively treated for bipolar disorder or depression in the past may use that medication during pregnancy unless contraindications exist. Treatment of bipolar disorder should not be discontinued during pregnancy or postpartum (ACOG 2023). When treatment is initiated for the first time during pregnancy, agents other than lithium are preferred by some guidelines (BAP [McAllister-Williams 2017]; NICE 2020). However, lithium may be an option for pregnant patients diagnosed with bipolar disorder with mania who have no prior medication history. The lowest effective dose without underdosing is recommended. Consider additional folic acid to reduce the risk of congenital cardiac defects (ACOG 2023). Maintain adequate hydration during lithium therapy (NICE 2020).
Lithium is present in breast milk.
Multiple reports summarize data related to the presence of lithium in breast milk (Gehrmann 2021; Heinonen 2022; Imaz 2019; Imaz 2021; Newmark 2019).
• A systematic review provides data collected from 39 mother-infant pairs compiled from 13 publications. Breast milk was sampled between postpartum days 1 and 385 following maternal doses of lithium 400 to 1,500 mg/day. Lithium breast milk concentrations ranged from 0.1 mEq/L (sampled 52 weeks' postpartum following a maternal dose of 600 mg/day) to 0.69 mEq/L (sampled at 4 weeks' postpartum following a maternal dose of 800 mg/day). However, breast milk levels were not reported in all studies and sampling across studies was not standardized. The infant plasma to maternal plasma drug concentration ratio (I/P ratio) was reported from 47 samples and ranged from 0.04 to 2 with samples taken from 1 to 52 days after birth. Adverse events in breastfed infants included transient lithium toxicity (n = 2; recovered after breastfeeding discontinued); mild hypotonia (n = 2; occurring during first 2 days of life in one case and at 2 months of age in the other case); weight loss within 1 week of birth (n = 2), renal changes (creatinine and/or urea nitrogen increased, n = 2), and transient hypothyroid (n = 1) (Imaz 2019).
• The relative infant dose (RID) of lithium was calculated by the authors of one study (also included in the Imaz 2019 review). Sampling of breast milk occurred at various times and infant ages, and the RID had a wide range (0% to 30%). In one case, the maternal dose was lithium 600 mg daily; lithium was not detected in breast milk on postpartum day 9 (5 samples over 24 hours), week 6 postpartum (5 samples over 24 hours), or 8 months (2 samples taken 2 and 8 hours after the maternal dose). However, a second mother also taking lithium 600 mg daily had an RID of 15% when sampling occurred at 0, 3, and 6 hours following the maternal dose on postpartum day 5 and an RID of 6.5% when sampling occurred 21 days postpartum (6.5 and 10.5 hours after the dose). The highest RID (21% to 30%) was observed following a daily maternal dose of lithium 1,500 mg when sampling occurred 2 and 5 hours after the dose on postpartum day 5. Adverse events were not observed in the 11 infants included in this report (Moretti 2003). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Anderson 2021). When the RID is >25%, breastfeeding should generally be avoided (Anderson 2016; Ito 2000).
• A retrospective study followed 30 infants exposed to lithium in utero and via breast milk over a median of 40 days (range 8 to 364 days) after birth. Lithium was measured in the umbilical cord at delivery then in infant serum at ~2, 4, and 8 weeks of age. The highest I/P ratio was observed at 1 to 2 weeks of age (mean 0.37) and decreased over time. Plasma sodium, potassium, creatinine, thyroid-stimulating hormones, and thyroid hormone concentrations in the infants were within normal ranges. Inadequate growth was observed in ~25% of the infants during their first month of life. In 4 cases, mothers were advised to decrease breastfeeding and increase feeding via formula due to elevated neonatal serum lithium concentrations (n = 2), poor infant growth (n = 1), or polypharmacy (n = 1). Two infants had lithium concentrations within the therapeutic range, which were decreased when breastfeeding was reduced (Heinonen 2022).
Recommendations related to the use of lithium while breastfeeding vary by guideline (ACOG 2023; BAP [McAllister-Williams 2017], CANMAT/ISBD [Yatham 2018]); breastfeeding is not recommended by the manufacturer. It is suggested that only patients who are clinically stable, adherent to treatment, and delivered a full-term healthy infant should consider breastfeeding (Hermann 2019). The RID of lithium varies widely and infant serum levels of lithium can reach up to 50% of the maternal levels; therefore, an infant exposed to lithium via breast milk requires close monitoring (ACOG 2023; BAP [McAllister-Williams 2017]; Hermann 2019). It is suggested to monitor mother and infant lithium levels at delivery, then 48 hours and 10 days postpartum (or 10 days after starting lithium if initiated postpartum). In addition, monitor infant weight, neurodevelopment, thyroid, and renal function. Infant lithium levels should continue to be monitored in the presence of lithium toxicity or when concentrations are >0.3 mEq/L (Imaz 2019). Signs of lithium toxicity in a breastfed infant may include cyanosis, ECG changes, hypertonia, or hypothermia; discontinue breastfeeding if toxicity occurs in the breastfed infant.
Supplementing breast milk with formula in patients who wish to breastfeed during lithium therapy will lower infant exposure. Bottle feeding overnight by the patient’s partner or other support person will also help maintain maternal sleep preservation and mood stabilization (ACOG 2023; CANMAT/ISBD [Yatham 2018]; Hermann 2019).
May be taken with meals to avoid GI upset; maintain adequate salt and fluid intake.
Renal function including BUN and SCr (baseline, every 2 to 3 months during the first 6 months of treatment, then once a year in stable patients or as clinically indicated); fluid status; pediatric patients may require more frequent checks); serum electrolytes (baseline, then periodically), serum calcium (baseline, 2 to 6 weeks after initiation, then every 6 to 12 months; repeat as clinically indicated; if discontinued due to hypercalcemia, monitor weekly for 1 month for return to baseline) (Broome 2011); signs and symptoms of hypercalcemia (eg, fatigue, weakness, abdominal pain, constipation, nephrolithiasis, bone pain); thyroid (baseline, 1 to 2 times with in the first 6 months of treatment, then once a year in stable patients or as clinically indicated); PTH as clinically indicated; ECG with rhythm strip (baseline for all patients >40 years of age or if underlying cardiac risk factors, repeat as clinical indicated), CBC with differential (baseline, repeat as clinically indicated) (APA 2002; Mehta 2017); serum lithium levels once weekly until both patient's clinical status and levels are stable, then repeat levels every 3 to 6 months or as clinically indicated [APA 2002; NICE 2022]; closely monitor in patients with significant renal or cardiovascular disease, debilitation, dehydration, sodium depletion, or those taking concomitant medications that impact renal function); weight (baseline, then periodically) (APA 2002; Mehta 2017); polyuria; signs of lithium toxicity (eg, diarrhea, vomiting, tremor, mild ataxia, drowsiness, muscular weakness).
Additional testing based on reproductive status:
Patients who could become pregnant: Pregnancy test prior to treatment (BAP [McAllister-Williams 2017]).
Patients planning to become pregnant: Baseline lithium blood levels and SCr prior to conception while symptomatically stable (ACOG 2023; Wesseloo 2017).
Pregnant patients: Lithium blood levels every 2 to 4 weeks until 34 weeks' gestation, then at least once weekly until delivery, at delivery, twice a week during the first 2 weeks' postpartum, then again at 4 weeks' postpartum. Increase the frequency of SCr and BUN monitoring if history of preterm birth, preeclampsia, dehydration, or other conditions that may affect renal function are present (Hermann 2019; Wesseloo 2017).
Monitor symptom improvement in conjunction with serum concentrations to guide dose adjustments. Obtain 2 consecutive serum concentrations in the therapeutic range during the acute phase, then monitor regularly (ie, every 3 to 6 months).
Timing of serum samples: A 12-hour trough level is preferred, but in some circumstances (eg, 3 times a day dosing, limited lab hours) it may be drawn 8 to 12 hours post dose. Check levels ~5 days after a dosage adjustment (CANMAT [Yatham 2018]; manufacturer's labeling).
Therapeutic concentrations:
Bipolar disorder:
Acute mania: 0.8 to 1.2 mEq/L (SI: 0.8 to 1.2 mmol/L); some guidelines recommend lower target serum concentrations (eg, 0.4 to 0.8 mEq//L [SI: 0.4 to 0.8 mmol/L]) for older adults.
Maintenance: 0.6 to 1 mEq/L (SI: 0.6 to 1 mmol/L); a higher rate of relapse is described in subjects who are maintained at <0.6 mEq/L (SI: <0.6 mmol/L). Some guidelines recommend targeting the lower end of the range for older adults (CANMAT [Yatham 2018]).
Cluster headache, prevention: 0.4 to 0.8 mEq/L (SI: 0.4 to 0.8 mmol/L); must not exceed 1.2 mEq/L (SI: 1.2 mmol/L) (EAN [May 2023]; May 2024).
Major depressive disorder: 0.6 to 0.9 mEq/L (SI: 0.6 to 0.9 mmol/L) (NICE 2022; VA/DoD 2022). In patients >65 years, consider targeting lowering levels (eg, 0.4 to 0.6 mEq/L [SI: 0.4 to 0.6 mmol/L]) (NICE 2022).
Toxic concentrations
>1.5 mEq/L (SI: >1.5 mmol/L): Early signs and symptoms of intoxication may include marked tremor, nausea, diarrhea, blurred vision, vertigo, confusion, and decreased deep tendon reflexes (APA 2002).
>2.5 mEq/L (SI: >2.5 mmol/L): Intoxication symptoms may progress to include severe neurological complications, seizures, coma, cardiac dysrhythmia, and permanent neurological impairment (APA 2002).
>3.5 mEq/L (SI: >3.5 mmol/L): Potentially lethal toxicity (Mitchell 2001).
Note: A 10% to 26% increase of a 12-hour serum concentration can be expected with once-daily dosing compared to a 12-hour serum concentration checked of an equal dose that is given twice daily (Mitchell 2001; Singh 2011).
The precise mechanism of action in mood disorders is unknown. Traditionally thought to alter cation transport across cell membranes in nerve and muscle cells, influence the reuptake of serotonin and/or norepinephrine, and inhibit second messenger systems involving the phosphatidylinositol cycle (Ward 1994). May also provide neuroprotective effects by increasing glutamate clearance, inhibiting apoptotic glycogen synthase kinase activity, increasing the levels of antiapoptotic protein Bcl-2 and, enhancing the expression of neurotropic factors, including brain-derived neurotrophic factor (Sanacora 2008).
Absorption: Rapid and complete
Distribution: Vd: Initial: 0.307 L/kg; Vdss: 0.7 to 1 L/kg; decreased in elderly patients (Ward 1994)
Protein binding: Not protein bound
Metabolism: Not metabolized (Ward 1994)
Bioavailability: 80% to 100% (Ward 1994)
Half-life elimination:
Pediatric patients 7 to 17 years: t1/2(beta): 27 hours (Findling 2010)
Adults: 18 to 36 hours; prolonged in elderly patients (~28.5 hours) (Ward 1994)
Time to peak, serum: Immediate release: ~0.5 to 3 hours; Extended release: 2 to 6 hours; Solution: 15 to 60 minutes
Excretion: Urine (primarily; unchanged drug); sweat, saliva, and feces (negligible amounts)
Clearance: 80% of filtered lithium is reabsorbed in the proximal convoluted tubules; decreased in elderly patients secondary to age-related decreases in renal function (Ward 1994)
Pediatric: In pediatric patients, great variability in clearance was found across subjects with linear pharmacokinetics correlated to fat-free mass (Findling 2010).
Older adult: Elderly patients receiving lithium may have a decreased glomerular filtration rate and decrease in renal plasma clearance (13.7 mL/minute) (Ward 1994).
