lithium (Rx)

>10%

Leukocytosis (most patients)

Polyuria/polydypsia (30-50%)

Dry mouth (20-50%)

Hand tremor (45% initially, 10% after 1 year of treatment)

Confusion (40%)

Decreased memory (40%)

Headache (40%)

Muscle weakness (30% initially, 1% after 1 year of treatment)

Electrocardiographic (ECG) changes (20-30%)

Nausea, vomiting, diarrhea (10-30% initially, 1-10% after 1-2 years of treatment)

Hyperreflexia (15%)

Muscle twitch (15%)

Vertigo (15%)

1-10%

Extrapyramidal symptoms, goiter (5%)

Hypothyroidism (1-4%)

Acne (1%)

Hair thinning (1%)

Frequency Not Defined

Coma

Lethargy

Seizures

Renal toxicity

Contraindications

Documented hypersensitivity

Severe cardiovascular disease

Pregnancy in 1st trimester

Unstable renal function, sodium depletion, severe dehydration

Severe debilitation

Cautions

Cardiovascular disease; reports of possible association between lithium treatment and unmasking of Brugada syndrome (abnormal ECG and risk of sudden death)

Use with caution in patients with thyroid disease

Narrow therapeutic index

Risk of nephrogenic diabetes insipidus; such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity; condition is usually reversible when lithium is discontinued

Lithium-sensitive patients may experience toxicity symptoms with serum lithium concentrations of 1-1.5 mEq/L

Lithium toxicity is closely related to serum levels and can occur at therapeutic dosages; if manifestations of toxicity occur, discontinue for 24-48 hours, then resume at lower dosage

Mainitain geriatric patients on dosages that produce serum lithium concentrations at lower end of desired range

May cause central nervous system (CNS) depression and impair ability to operate heavy machinery

Hypercalcemia reported with or without hyperparathyroidism; women and older patients are possibly at greater risk; onset does not appear to be associated with duration of therapy

Monitor changes in renal function; chronic therapy may diminish renal concentrating ability; usually reversible when lithium therapy discontinued

Use caution in debilitated patients; may increase risk of lithium toxicity

Use with caution in patients at risk for suicide

The risk of lithium toxicity is increased in patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, and for patients receiving prescribed medications that may affect kidney function, such as angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), diuretics (loops and thiazides) and NSAIDs; for these patients, consider starting with lower doses and titrating slowly while frequently monitoring serum lithium concentrations and signs of lithium toxicity

Cases consistent with nephrotic syndrome reported with use of lithium; discontinuation of lithium in patients with nephrotic syndrome has resulted in remission of nephrotic syndrome

Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine ,creatinine clearance, or proteinuria); during lithium therapy, progressive or sudden changes in renal function, even within normal range, indicate the need for re-evaluation of treatment

An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN, and FBS) has reported in a few patients treated with lithium plus a neuroleptic, most notably haloperidol; in some instances, the syndrome was followed by irreversible brain damage; because of possible causal relationship patients receiving such combined therapy or patients with organic brain syndrome or other CNS impairment should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear; encephalopathic syndrome may be similar to or the same as Neuroleptic Malignant Syndrome (NMS)

Lithium may prolong effects of neuromuscular blocking agents; neuromuscular blocking agents should be given with caution to patients receiving lithium

Mechanism of Action

Inhibits postsynaptic D2 receptor supersensitivity

Alters cation transport in nerve and muscle cells and influences reuptake of serotonin or norepinephrine

Inhibits phosphatidylinositol cycle second messenger systems

Absorption

Bioavailability: Immediate release, 95-100%; extended release, 60-90%

Onset: Initial antimanic effect, 5-7 days; full effect, 10-21 days

Peak serum time: Immediate release, 0.5-2 hr; extended release, 4-12 hr

Peak plasma concentration: 0.4-0.9 mEq/L

Steady-state therapeutic plasma concentration: 0.5-1.3 mEq/L

Distribution

Vd: Approximates total body water (0.7-1 L/kg)

Metabolism

Not metabolized

Elimination

Half-life: 18-24 hr; up to 36 hr with advanced age or renal impairment

Dialyzable: Yes (hemodialysis, 50-90 mL/min; peritoneal dialysis, 13-15 mL/min)

Renal clearance: 20-40 mL/min

Excretion: Urine (95-99%)