Lithium

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)

FDA INDICATIONS:
1) Acute mania
2) Bipolar Disorder Maintenance in children and adults

 

Additional Information:

 

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

Lithium Toxicity

Lithium ToxicityCausesPresentation Treatment
OverdoseNauseaHold/Discontinue Lithium
DehydrationVomitingMonitor lithium levels every 2-4 hours
Hyponatremia (low sodium)DiarrheaIntravenous (IV) Fluids
Low GFR (Glomerular Filtration Rate)AtaxiaHemodialysis recommended if Lithium level >2.5 mEq/L with signs of neurotoxicity
Renal Impairment/Failure/DiseaseConfusionHemodialysis recommended if no improvement with IV fluids
Drug InteractionsTremorHemodialysis 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 MonitoringTarget Lithium LevelRecommended Labs
Acute Mania0.8-1.2mEq/LBaseline: CBC, CMP, Cr, BUN, TSH, Weight, EKG (in pts>50yo or with cardiac disease)
Maintenance0.6-1.0 mEq/LAfter 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

References:

  1. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  2. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  3. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
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  8. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  9. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.