Mechanism of Action

Gold-standard mood stabilizer for bipolar I — treats acute mania and prevents both manic and depressive episodes. It modulates neurotransmitter release and enhances serotonin function (exact mechanism incompletely understood). It is NOT an antipsychotic. The therapeutic range is one of the narrowest in psychiatry: 0.6–1.2 mEq/L (trough drawn 8–12 h after the last dose). The key pharmacokinetic fact: lithium is a salt cleared almost entirely by the kidneys and competes with SODIUM for renal reabsorption — when sodium drops or the patient dehydrates, the kidneys retain lithium in its place and levels climb toward toxicity.

1.5 (moderate toxicity)

2.0 (severe)

Sub-therapeutic

Therapeutic window

Toxic

0.6

1.2

2.5

mEq/L

Common Medications

lithium carbonatePrototype

single high-yield agent

Indications

bipolar I disorder

mood stabilization

acute mania

target 1.0–1.2 mEq/L

maintenance / relapse prevention

target 0.6–1.0 mEq/L

Side Effects

fine hand tremor

EXPECTED at therapeutic levels — do not confuse with coarse toxic tremor

polyuria

lithium-induced nephrogenic diabetes insipidus with long-term use

polydipsia

weight gain

long-term therapeutic effect, not toxicity

hypothyroidism

lithium suppresses thyroid; rising TSH on long-term therapy

Contraindications & Interactions

NSAIDs Hallmark

reduce renal lithium clearance — highest-yield OTC interaction; raises level toward toxicity

thiazide diuretics

cause sodium loss → kidneys retain lithium

ACE inhibitors

raise lithium level

dehydration

vomiting, diarrhea, sweating, heat — concentrate lithium

low-sodium diet

sodium loss raises lithium

Administration & Monitoring

draw trough 8–12 h after last dose0.6–1.2 mEq/L

standardized ~12 h post-dose; NOT 2 h (that is the peak)

level every 1–2 weeks at initiation

then every 2–3 months once stable

baseline and periodic TSH

lithium causes hypothyroidism

monitor BUN and creatinine

renally cleared; can impair kidney function

monitor serum sodium

hyponatremia raises lithium toxicity risk

hold dose if toxicity suspectedHold

draw a STAT level

IV normal saline for toxicity

promotes renal excretion; no antidote — supportive care

hemodialysis for severe toxicity

definitive for level > 4.0 mEq/L, severe neuro signs, or renal failure; watch for rebound rise

Patient Teaching

drink 2–3 L of fluid daily

consistent intake; replace losses from heat/exercise

keep consistent dietary sodium

do not start a low-sodium diet without provider guidance

avoid OTC NSAIDs

call provider before taking ibuprofen

report persistent GI symptoms

vomiting/diarrhea can trigger toxicity

report coarse tremor or slurred speech

toxicity signs

never double a missed dose

increase fluids in heat or heavy sweating

dehydration concentrates lithium

Report Nowescalate immediately

coarse hand tremor Hallmark

EARLY toxicity (1.2–1.5 mEq/L) — distinguishes from expected fine tremor

persistent vomiting and diarrhea

early GI toxicity; also worsens it by causing more sodium/fluid loss

ataxia

moderate toxicity (1.5–2.0 mEq/L)

slurred speech

moderate toxicity

confusion

moderate toxicity; drowsiness

seizures

severe toxicity (> 2.0 mEq/L)

cardiac dysrhythmias

severe toxicity

serum lithium > 1.5 mEq/L> 1.5 mEq/L

hold dose; hemodialysis for severe (e.g. > 4.0 mEq/L or severe neuro signs)

Clinical Pearl

Lithium is sodium's salt twin — wherever sodium goes, lithium follows. Lose sodium (dehydration, low-salt diet, thiazides, NSAIDs) and lithium climbs toward toxicity. Watch the tremor: FINE is expected, COARSE is toxic. Therapeutic 0.6–1.2 mEq/L, trough drawn 8–12 h after the dose.