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Lithium (Li)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Therapeutic Drug Monitoring – Key Marker for Bipolar Disorder Management & Toxicity)

Synonyms

  • Lithium
  • Serum lithium
  • Lithium level
  • Li⁺ ion concentration

Units of Measurement

  • µmol/L
  • mmol/L
  • mg/dL
  • mg/100 mL
  • mg%
  • mg/L
  • µg/mL
  • mEq/L

Molecular Weight

Lithium ion = 6.94 g/mol

Key Unit Conversions

1. Mass ↔ Molar

1 mmol/L = 6.94 mg/L
1 µmol/L = 0.00694 mg/L
1 mg/L = 0.144 mmol/L
1 mg/dL = 10 mg/L = 1.44 mmol/L

2. mEq/L

Lithium is monovalent →
1 mmol = 1 mEq

1 mEq/L = 1 mmol/L

3. µg/mL

1 µg/mL = 1 mg/L

4. mg%

mg% = mg/dL

Description

Lithium is a monovalent cation (Li⁺) used as a mood stabilizer in psychiatry.
Major uses:

  • Bipolar disorder (mania & maintenance)
  • Schizoaffective disorder
  • Aggression reduction
  • Adjunct in depression (augmentation therapy)

Lithium has a narrow therapeutic window, requiring routine monitoring to prevent:

  • Neurotoxicity
  • Renal toxicity
  • Thyroid dysfunction

Mechanism of Action

  • Inhibits inositol monophosphatase → affects second messengers
  • Modulates GSK-3β, serotonin, norepinephrine pathways
  • Stabilizes neuronal firing
  • Reduces suicide risk significantly

Clinical Significance

HIGH Lithium (Toxicity)

(Major clinical concern)

1. Mild Toxicity

  • >1.5 mEq/L (mmol/L)
    Symptoms:
  • Tremor
  • Weakness
  • Nausea
  • Polyuria / polydipsia

2. Moderate Toxicity

  • 1.5 – 2.5 mEq/L
    Symptoms:
  • Ataxia
  • Confusion
  • Slurred speech
  • Agitation
  • GI upset

3. Severe Toxicity

  • >2.5 mEq/L
    Symptoms:
  • Seizures
  • Coma
  • Arrhythmias
  • Renal failure
  • Neurotoxicity

Causes of Elevated Lithium

  • Dehydration
  • Renal impairment
  • Drug interactions (NSAIDs, ACEI, thiazides)
  • Acute overdose
  • Sodium depletion

LOW Lithium

  • Subtherapeutic dose
  • Non-adherence
  • Rapid renal clearance
  • Drug interactions (caffeine, theophylline)

Clinical consequence: poor mood stabilization.

Therapeutic Range

(APA psychiatric guidelines + Mayo + ARUP)

Acute Mania

  • 0.8 – 1.2 mEq/L (mmol/L)

Maintenance Therapy

  • 0.6 – 1.0 mEq/L

Elderly

  • 0.4 – 0.8 mEq/L (increased sensitivity)

Toxic Levels

  • >1.5 mEq/L early toxicity
  • >2.5 mEq/L severe/life-threatening

Reference Intervals (non-treated individuals)

  • <0.2 mEq/L (essentially undetectable)

Diagnostic Uses

1. Therapeutic Drug Monitoring

Check levels:

  • 12 hours after last dose (“trough level”)
  • Weekly during initiation
  • Every 3 months during maintenance
  • More frequently in elderly or renal impairment

2. Suspected Lithium Toxicity

Measure urgently in:

  • Confusion
  • Ataxia
  • GI symptoms
  • Dehydration

3. Renal Function Assessment

Lithium clearance depends on kidney function
→ Must monitor creatinine & eGFR.

4. Thyroid Monitoring

Lithium can cause:

  • Hypothyroidism
  • Goiter
    → TSH testing recommended.

5. Pregnancy

Levels fluctuate; dose adjustments needed.

Analytical Notes

  • Serum lithium (not plasma) preferred
  • Collect at 12-hour post-dose
  • Hemolysis has minimal effect
  • Interferences: sodium changes, dehydration
  • Lithium heparin tubes should NOT be used (falsely high)

Clinical Pearls

  • Lithium toxicity mimics stroke - ataxia, slurred speech, confusion.
  • Dehydration is the most common cause of sudden toxicity.
  • NSAIDs, ACE inhibitors & thiazide diuretics increase lithium levels.
  • Caffeine & theophylline lower lithium levels.
  • Hemodialysis is required for severe toxicity (>3.5–4 mEq/L).
  • Lithium reduces suicide risk by >60% — unique among mood stabilizers.

Interesting Fact

Lithium is the lightest metal in the periodic table, and uniquely, it is a natural element with powerful mood-stabilizing properties discovered serendipitously in the 1940s.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Therapeutic Drug Monitoring
  2. APA Guidelines - Bipolar Disorder Management
  3. Mayo Clinic Laboratories - Lithium Level
  4. ARUP Consult - Psychiatric Drug Monitoring
  5. AACT Toxicology Guidelines - Lithium Overdose
  6. MedlinePlus / NIH - Lithium Test

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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