Clinical Features of Chronic Lithium Toxicity
Chronic lithium toxicity presents predominantly with neurological manifestations that are typically more severe than acute toxicity, even at lower serum levels, because prolonged tissue exposure causes greater cellular damage. 1, 2
Neurological Features (Most Prominent)
The central nervous system is the primary site of toxicity in chronic lithium poisoning 3:
Early neurological signs:
- Tremor (fine hand tremor progressing to coarse tremor) 4, 5
- Ataxia and lack of coordination 5
- Drowsiness and confusion 5, 3
- Slurred speech 5
- Muscular weakness 5
Progressive neurological manifestations:
- Hyperreflexia and muscle hyperirritability (fasciculations, twitching, clonic movements) 5
- Choreoathetotic movements 5
- Seizures (epileptiform) 5
- Altered mental status ranging from psychomotor retardation to stupor and coma 5
- Downbeat nystagmus 5
- Blackout spells 5
Gastrointestinal Features
These GI symptoms occur early but are less reliable indicators in chronic toxicity compared to neurological signs 5.
Renal Manifestations
- Polyuria and polydipsia (from nephrogenic diabetes insipidus) 4, 5
- Large output of dilute urine 5
- Acute renal failure (can occur with severe intoxication) 6
- Oliguria (in advanced toxicity) 5
Chronic lithium use causes nephrogenic diabetes insipidus, which paradoxically increases toxicity risk through volume depletion 3.
Cardiovascular Features
- Cardiac arrhythmias 5, 6
- Sinus node dysfunction with severe bradycardia (may result in syncope) 5
- Hypotension 5
- ECG changes (T-wave flattening, isoelectricity, or inversion) 5
Endocrine Abnormalities
Critical Distinguishing Features of Chronic vs. Acute Toxicity
Patients with chronic toxicity during maintenance therapy have significantly more severe symptoms than those with acute overdose, even at similar or lower serum lithium levels 1. This occurs because:
- Chronic exposure allows extensive tissue distribution and intracellular accumulation 2
- Tissue lithium concentrations remain elevated despite falling serum levels 2
- Neurological damage is proportional to duration of exposure, not just peak concentration 1, 3
Serum Level Correlation (Important Caveat)
While toxicity risk increases above 1.5 mEq/L, patients with chronic exposure may exhibit severe toxic signs at levels below 1.5 mEq/L 5. The FDA emphasizes that lithium-sensitive patients can show toxicity below typical thresholds 5. Serum levels above 2.0 mEq/L indicate serious toxicity, and levels above 3.0 mEq/L produce multi-organ system involvement 7, 5.
Persistent Neurological Sequelae
Chronic lithium poisoning can result in permanent cerebellar dysfunction and cognitive impairment, requiring prolonged hospitalization 3. This persistent neurological deficit appears uncommon in uncomplicated acute poisoning but is a significant risk in chronic toxicity 3.
Special Neurological Syndrome
Pseudotumor cerebri (increased intracranial pressure with papilledema) can occur and, if undetected, may cause permanent blindness from optic atrophy 5. Lithium should be discontinued if this syndrome develops 5.