HALF-LIFE: 18-24 hours
INITIAL DOSE: 300mg-600mg PO per day (divided doses)
TARGET DOSING RANGE: 600mg-1,200mg per day (Target level 0.8-1.0 mEq/L)
BEST TIME TO DOSE: Any
TYPICAL DOSING: Initial 300mg-600mg at bedtime or divided in two doses. Gradually increase dose to target serum level of 0.6-1.0 mEq/L. Max dose is generally 2,400mg/day.
PREGNANCY: Avoid if possible (but not a contraindication) – Risk of Epstein Anomaly (cardiac defect)
BREASTFEEDING: Avoid if possible (but not a contraindication)
1) Acute mania
2) Bipolar Disorder Maintenance in children and adults
Lithium’s interactions with the brain are complex and include:
Desensitizing presynaptic 5HT-1A auto receptors in the raphe nuclei and thereby increasing serotonin release
Decoupling G-protein linked production of second messengers
Directly increasing transcription of fast response genes (e.g. KREB, PHOS, and JUN)
Proposed Mechanisms of Action of Lithium:
Alters sodium transport in myocytes/neurons
Alters metabolism of catecholamines (DA, NE, Epinephrine)
Alters intracellular signaling via second messengers (IP3 and PKC pathways)
INTERESTING FACTS ABOUT LITHIUM:
Lithium is a cation metal first used in the 19th century to treat gout and discovered by John Cade in 1949 to exert anti-manic effects
Lithium does not undergo metabolism and is not protein bound. It is cleared via the kidneys.
Benign leukocytosis is common due to demarginalization of WBCs
Despite being highly effective, lithium is not widely used due to its narrow therapeutic index. Optimal plasma concentrations for treatment of bipolar mood disorder are 0.8 to 1.2 meq/L, however, toxic signs and symptoms may begin at concentrations as low as 1.5 meq/L and serious toxicity with risk of permanent neurological injury may occur at concentrations as low as 2.0 meq/L.
Lithium may worsen skin conditions such as acne and psoriasis
Lithium use during the first trimester of pregnancy may be associated with an increased risk of Epstein’s anomaly (downward displacement of tricuspid valve into a malfunctioning right ventricle) although this is controversial. Note that lithium has been safely used in pregnancy in select patients.
Lithium is easily dialyzed and can be administered to patients on hemodialysis (Give dose after dialysis treatment)
Caffeine may decrease lithium levels
Lithium + Haloperidol may increase the risk of NMS and delirium
Lithium may cause abnormal involuntary movements
Lithium may increase the risk of serotonin syndrome if administered with serotonergic agents
An increase or decrease of 300mg/day changes serum Li levels approximately 0.25 mEq/L (rough estimate)
Effective for chronic suicidal thoughts in bipolar and unipolar depression
Effective for aggressive and violent behaviors
Increased risk of nephrogenic diabetes insipidus (usually reversible) – may be reduced with once daily dosing
Propranolol is an effective treatment for tremors associated with lithium
Bradycardia, cardiac arrhythmia, sinus node dysfunction may be seen with lithium therapy
|Dehydration||Vomiting||Monitor lithium levels every 2-4 hours|
|Hyponatremia (low sodium)||Diarrhea||Intravenous (IV) Fluids|
|Low GFR (Glomerular Filtration Rate)||Ataxia||Hemodialysis recommended if Lithium level >2.5 mEq/L with signs of neurotoxicity|
|Renal Impairment/Failure/Disease||Confusion||Hemodialysis recommended if no improvement with IV fluids|
|Drug Interactions||Tremor||Hemodialysis recommended if Lithium level >4.0 mEq/L|
|Diuretics (except loop diuretics)||Slurred Speech|
|NSAIDs (except aspirin)||Seizures|
|ACE Inhibitors||Abnormal Movements|
Lithium Level Monitoring
|Lithium Monitoring||Target Lithium Level||Recommended Labs|
|Acute Mania||0.8-1.2mEq/L||Baseline: CBC, CMP, Cr, BUN, TSH, Weight, EKG (in pts>50yo or with cardiac disease)|
|Maintenance||0.6-1.0 mEq/L||After 1 week, 1 month, 6 months, and 12 months of starting lithium: Lithium Level, TSH, BUN/Cr, Electrolytes, monitor weight|
|Every 6-12 months: Lithium Level, TSH, BUN/Cr, Electrolytes, monitor weight|
|NOTE: Check Lithium levels after 4-5 half lives (blood should be collected prior to next dose); Also check lithium levels after dosage changes, addition of other drugs, or if suspecting toxicity|
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