Symptoms of Lithium Toxicity at High Levels
Lithium toxicity presents with progressively severe symptoms that correlate with serum levels, beginning with gastrointestinal and neurological manifestations at levels >1.5 mEq/L and progressing to life-threatening multi-organ dysfunction at levels >3.0 mEq/L.
Early/Mild Toxicity (Levels 1.5-2.0 mEq/L)
The initial warning signs include:
- Tremor, nausea, diarrhea, and polyuria-polydipsia are the hallmark early symptoms 1
- Diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination may appear even below 2.0 mEq/L 2
- Fine hand tremor, polyuria, and mild thirst commonly occur during initial therapy and may persist throughout treatment 2
Moderate Toxicity (Levels 2.0-3.0 mEq/L)
As levels rise, neurological symptoms become more prominent:
- Giddiness, ataxia, blurred vision, tinnitus, and large output of dilute urine emerge at higher levels 2
- Slurred speech, dizziness, vertigo, confusion, and somnolence develop 2
- Muscle hyperirritability manifesting as fasciculations, twitching, and clonic movements of limbs 2
Severe Toxicity (Levels >3.0 mEq/L)
At levels above 3.0 mEq/L, a complex clinical picture involving multiple organ systems develops 2:
Neurological Manifestations
- Stupor, coma, and psychomotor retardation 2
- Epileptiform seizures and blackout spells 2
- Incontinence of urine or feces 2
- Hyperactive deep tendon reflexes and choreo-athetotic movements 2
- Acute dystonia and downbeat nystagmus 2
Cardiovascular Complications
- Cardiac arrhythmias, hypotension, and peripheral circulatory collapse 2
- Severe bradycardia and sinus node dysfunction (which may result in syncope) 2
- Advanced AV block requiring urgent intervention 1
Renal Effects
- Oliguria, albuminuria, and glycosuria 2
- Impaired renal concentrating ability contributing to dehydration 3
Critical Clinical Distinction: Acute vs. Chronic Toxicity
An important caveat is that symptom severity does not always correlate directly with serum lithium levels, particularly when comparing acute overdose to chronic toxicity 1, 4:
- Patients with chronic toxicity (developing during maintenance therapy) typically have more severe symptoms than those with acute overdose, even at similar serum levels 4, 5
- Acute intoxication patients may have mild symptoms despite potentially lethal levels (>3.5 mEq/L) 4
- Chronic intoxication carries higher risk of permanent neurological sequelae and prolonged recovery 5
Additional Organ System Effects
Beyond the primary manifestations, lithium toxicity can affect:
- Thyroid: Hypothyroidism with goiter, or paradoxically hyperthyroidism (which itself can precipitate toxicity) 2, 6
- Dermatologic: Hair thinning, alopecia, skin anesthesia, and psoriasis exacerbation 2
- Autonomic: Blurred vision and dry mouth 2
- Metabolic: Dehydration, weight loss, and transient hyperglycemia 2
Risk Factors That Lower Toxicity Threshold
Patients may exhibit toxic signs at levels below 1.5 mEq/L if they are sensitive to lithium or have predisposing factors 2: