What are the typical signs of lithium toxicity in an adult patient with bipolar disorder?

Typical Signs of Lithium Toxicity

Lithium toxicity presents with a predictable progression of symptoms that correlate with serum levels: early signs include diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination (occurring even below 2.0 mEq/L), progressing to giddiness, ataxia, blurred vision, tinnitus, and polyuria at higher levels, with severe toxicity above 3.0 mEq/L causing multi-organ dysfunction. 1

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

The FDA label explicitly identifies the earliest manifestations of lithium toxicity that can occur at levels below 2.0 mEq/L 1:

• Gastrointestinal symptoms: Diarrhea, vomiting, nausea, and anorexia are often the first indicators 1
• Neuromuscular symptoms: Drowsiness, muscular weakness, and lack of coordination appear early 1
• Fine hand tremor may intensify beyond the mild tremor seen during normal therapy 1

Critical caveat: Patients sensitive to lithium may exhibit toxic signs at serum levels below 1.5 mEq/L, meaning toxicity is not solely determined by absolute serum concentration 1

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

As lithium levels rise, neurological symptoms become more prominent 1:

• Giddiness and ataxia (impaired coordination and balance) 1
• Blurred vision 1
• Tinnitus (ringing in the ears) 1
• Polyuria (large output of dilute urine) 1
• Slurred speech 1, 2
• Confusion and cognitive impairment 1, 2

Severe Toxicity (Serum Levels >3.0 mEq/L)

Serum lithium levels above 3.0 mEq/L produce a complex clinical picture involving multiple organs and organ systems 1:

• Central nervous system: Seizures, stupor, coma, severe confusion, psychomotor retardation 1
• Neuromuscular: Muscle hyperirritability (fasciculations, twitching, clonic movements), hyperactive deep tendon reflexes, choreo-athetotic movements 1
• Cardiovascular: Cardiac arrhythmias, hypotension, peripheral circulatory collapse, severe bradycardia with syncope 1, 3
• Renal: Oliguria, albuminuria 1
• Incontinence of urine or feces 1

Neurological Manifestations Requiring Immediate Recognition

Several neurological findings indicate serious toxicity 1, 2:

• Cerebellar signs: Ataxia, dysarthria, dysdiadochokinesis, past pointing 2, 4
• Movement disorders: Tremor progression, myoclonus, acute dystonia 1
• Altered mental status: Ranging from restlessness and confusion to stupor and coma 1
• Visual hallucinations may occur 2
• Downbeat nystagmus 1

Clinical Patterns of Toxicity

The presentation varies based on the pattern of lithium accumulation 5:

• Chronic toxicity (most common): Results from lithium intake exceeding elimination, typically due to impaired kidney function from volume depletion, nephrogenic diabetes insipidus, or drug interactions 5
• Acute-on-chronic toxicity: Occurs when patients on maintenance therapy experience acute overdose or precipitating factors 5
• Acute toxicity: Single large ingestion in lithium-naive patients 5

Important Monitoring Context

The American Academy of Child and Adolescent Psychiatry emphasizes that therapeutic monitoring is essential, with target levels of 0.8-1.2 mEq/L for acute mania and 0.6-0.8 mEq/L for maintenance 6. Serum lithium levels should not exceed 2.0 mEq/L during acute treatment 1.

Regular monitoring every 3-6 months should include lithium levels, renal function (BUN, creatinine), and thyroid function 7, 6. The narrow therapeutic index means toxicity can develop rapidly with changes in renal function, hydration status, or drug interactions 7, 5.

Persistent Neurological Sequelae

Critical warning: Some patients develop irreversible lithium-effectuated neurotoxicity (SILENT syndrome) with persistent cerebellar dysfunction even after lithium discontinuation, though this appears uncommon in uncomplicated acute poisoning 5, 4. Symptoms like slurring of speech and ataxia may persist despite lithium withdrawal and adequate supportive care 4.

Common Precipitating Factors

Clinicians must recognize conditions that precipitate toxicity 5, 2:

• Volume depletion from any cause (vomiting, diarrhea, fever, decreased oral intake) 5
• Lithium-induced nephrogenic diabetes insipidus creating a vicious cycle 5
• Drug interactions: NSAIDs, ACE inhibitors, thiazide diuretics, and other medications affecting renal function 5
• Intercurrent illness affecting hydration or renal function 5