Symptoms of Lithium Toxicity
Lithium toxicity presents with a spectrum of symptoms that correlate with serum levels, beginning with gastrointestinal and neuromuscular manifestations at lower toxic levels (>1.5 mEq/L) and progressing to severe neurological and multi-organ dysfunction at higher concentrations (>3.0 mEq/L). 1
Early Warning Signs (Levels 1.5-2.0 mEq/L)
The earliest indicators of lithium toxicity that should prompt immediate evaluation include: 1
- Gastrointestinal symptoms: Diarrhea, vomiting, nausea, and anorexia 1
- Neuromuscular effects: Muscular weakness, lack of coordination, and fine hand tremor (more pronounced than baseline) 1
- Central nervous system: Drowsiness and lethargy 1
These symptoms can occur at levels below 2.0 mEq/L and represent the critical window for intervention before severe toxicity develops. 1
Moderate Toxicity (Levels 2.0-3.0 mEq/L)
As lithium levels rise, additional neurological symptoms emerge: 1
- Cerebellar dysfunction: Giddiness, ataxia, and tremor progression 1
- Sensory disturbances: Blurred vision and tinnitus 1
- Renal effects: Large output of dilute urine (nephrogenic diabetes insipidus) 1
- Speech abnormalities: Slurred speech and dysarthria 1
- Cognitive changes: Confusion and psychomotor retardation 1
Severe Toxicity (Levels >3.0 mEq/L)
At serum levels above 3.0 mEq/L, a complex multi-organ clinical picture develops that can be life-threatening: 1
Neurological Manifestations
- Severe altered mental status: Confusion progressing to stupor and coma 1
- Seizure activity: Epileptiform seizures and blackout spells 1
- Movement disorders: Choreo-athetotic movements, muscle fasciculations, twitching, and clonic movements of entire limbs 1
- Acute dystonia and hyperactive deep tendon reflexes 1
- Incontinence of urine or feces 1
- Downbeat nystagmus 1
Cardiovascular Complications
- Cardiac arrhythmias 1
- Hypotension and peripheral circulatory collapse 1
- Sinus node dysfunction with severe bradycardia (potentially causing syncope) 1
Other Organ System Involvement
- Renal: Oliguria, albuminuria, glycosuria 1
- Autonomic: Dry mouth, blurred vision 1
- Dermatologic: Skin anesthesia 1
Critical Clinical Distinctions
An important caveat is that patients sensitive to lithium may exhibit toxic signs at serum levels below 1.5 mEq/L, making clinical assessment paramount over relying solely on laboratory values. 1
Acute vs. Chronic Toxicity Patterns
The clinical presentation differs significantly based on the pattern of intoxication: 2, 3
- Acute overdose: Patients frequently have milder symptoms despite potentially lethal serum levels (>3.5 mEq/L), with better outcomes and less likelihood of permanent sequelae 2
- Chronic toxicity (during maintenance therapy): More severe neurological and cardiovascular symptoms at lower serum levels, requiring more aggressive intervention including hemodialysis 2, 3
This distinction is crucial because chronic toxicity—the most common pattern—results from impaired elimination (often from volume depletion, renal impairment, or drug interactions) and carries higher risk of prolonged hospitalization and persistent neurological deficits. 3
Mimics and Differential Considerations
Lithium toxicity can present as drug-induced neurological dysfunction that mimics stroke, particularly with confusion, ataxia, and altered consciousness. 4 This underscores the importance of obtaining medication history and lithium levels in patients presenting with acute neurological changes.