What are the symptoms of lithium toxicity?

Symptoms of Lithium Toxicity

Lithium toxicity presents with a spectrum of symptoms that correlate with serum levels and chronicity of exposure, ranging from early gastrointestinal and neurological signs at therapeutic levels to life-threatening multi-organ dysfunction at severe levels. 1

Early Warning Signs (Serum Levels <2.0 mEq/L)

The earliest manifestations of lithium toxicity can occur even below 2.0 mEq/L and include: 1

• Diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination - these are critical early warning signs that should prompt immediate evaluation 1
• Fine hand tremor, polyuria, and mild thirst (may occur during initial therapy but can also signal toxicity) 1
• Transient nausea and general discomfort 1

Moderate Toxicity (Serum Levels 2.0-3.0 mEq/L)

As levels rise above 2.0 mEq/L, more pronounced symptoms emerge: 1

• Giddiness and ataxia 1
• Blurred vision 1
• Tinnitus 1
• Large output of dilute urine 1
• Slurred speech 1

Severe Toxicity (Serum Levels >3.0 mEq/L)

Levels above 3.0 mEq/L produce a complex multi-organ clinical picture: 1

Neurological Manifestations

• Confusion, stupor, and coma 1
• Seizures (epileptiform) 1
• Blackout spells 1
• Tremor and muscle hyperirritability (fasciculations, twitching, clonic movements) 1
• Hyperactive deep tendon reflexes 1
• Choreo-athetotic movements 1
• Acute dystonia 1
• Downbeat nystagmus 1
• Psychomotor retardation or restlessness 1
• Incontinence of urine or feces 1

Cardiovascular Symptoms

• Cardiac arrhythmias 1
• Hypotension 1
• Peripheral circulatory collapse 1
• Sinus node dysfunction with severe bradycardia (may result in syncope) 1

Gastrointestinal Symptoms

• Anorexia, nausea, vomiting, diarrhea 1

Renal Manifestations

• Oliguria 1
• Polyuria 1

Critical Distinction: Acute vs. Chronic Toxicity

The severity of symptoms depends not only on serum lithium levels but also on whether toxicity is acute or chronic: 2, 3

• Acute toxicity (following overdose) often produces milder symptoms despite potentially lethal serum levels (>3.5 mEq/L), and patients may not require hemodialysis 2
• Chronic toxicity (during maintenance therapy) produces more severe symptoms at lower serum levels and carries higher risk of permanent neurological sequelae 2, 4

Irreversible Neurological Sequelae

The most concerning long-term complication is persistent cerebellar dysfunction, particularly ataxia and dysarthria, which can occur after both acute overdose and chronic toxicity: 4

• These irreversible deficits greatly reduce quality of life and are difficult to manage 4
• Risk factors are often not well identified, making prevention through early recognition crucial 4

Important Clinical Caveats

• Patients sensitive to lithium may exhibit toxic signs at serum levels below 1.5 mEq/L 1
• Hydration status is critical in assessing toxicity risk, as dehydration from lithium-induced nephrogenic diabetes insipidus is a major predisposing factor 5, 6
• Chronic toxicity typically develops insidiously with silent renal impairment preceding overt symptoms, creating an accelerating vicious circle once moderate severity is reached 7
• The duration of lithium intoxication, not just peak level, influences severity of outcome 6