Clinical Information

HALF-LIFE: 18-24 hours


METABOLISM: None, excreted unchanged in kidneys

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)


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. An increase or decrease of 300mg/day changes serum Li levels approximately 0.25 mEq/L (rough estimate)

PREGNANCY: Avoid if possible (but not an absolute contraindication) – Risk of Epstein Anomaly (downward displacement of tricuspid valve into a malfunctioning right ventricle)

BREASTFEEDING: Avoid if possible (but not an absolute contraindication)

FDA Indications

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

Side Effects

Nausea, diarrhea, upset stomach, frequent urination (nephrogenic diabetes insipidus), increased thirst, tremors, headache, fatigue, lethargy, emotional blunting/flatness, worsening of acne, worsening of psoriasis, increased white blood cell count. Mild side effects are common when starting lithium (especially nausea, upset stomach, daytime fatigue) but typically go away after about 5 days of consistently taking the medication as prescribed. 

Drug Interactions

  • 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

The following medications/drugs commonly INCREASE lithium levels:

  • NSAIDs (e.g., naproxen, Ibuprofen)
  • Dehydration
  • Low sodium levels (hyponatremia)
  • ACE Inhibitors (e.g., Lisinopril)
  • Diuretics (e.g., thiazide and loop diuretics)

The following medications/substances commonly DECREASE lithium levels:

  • Caffeine
  • Theophylline
  • High sodium levels/high salt diet (e.g., hypernatremia)

Mechanism(s) of Action

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:

  1. Alters sodium transport in myocytes/neurons
  2. Alters metabolism of catecholamines (DA, NE, Epinephrine)
  3. Alters intracellular signaling via second messengers (IP3 and PKC pathways)

Additional Information

  • 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
  • Benign leukocytosis (elevated white blood cell count) is due to demarginalization of white blood cells (WBCs)
  • 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 is easily dialyzed and can be administered to patients on hemodialysis (Give dose after dialysis treatment)
  • Effective for chronic suicidal thoughts in bipolar and unipolar depression
  • Effective for aggressive and violent behaviors
  • 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


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