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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Therapeutic range 0.4–1.0 mmol/L (0.6–0.8 for maintenance, up to 1.0 in acute mania)
- Toxicity: >1.5 mmol/L (mild-moderate), >2.0 mmol/L (severe — neurotoxicity, seizures, coma)
- Common precipitants: dehydration (D&V, fever), renal impairment, NSAIDs, ACEi/ARBs, diuretics (especially thiazides)
- Monitoring: lithium levels every 3–6 months (12 hours post-dose), plus U&Es, TFTs, calcium every 6 months
- Severe toxicity (>2.0 mmol/L with symptoms): IV fluids + consider haemodialysis
Overview
Lithium is a mood stabiliser used primarily for bipolar affective disorder and augmentation in treatment-resistant depression. It has a very narrow therapeutic index, meaning small changes in serum levels can cause toxicity. Lithium is handled by the kidneys similarly to sodium — anything that reduces renal sodium excretion (dehydration, diuretics, ACE inhibitors) causes lithium retention and potentially toxicity. Chronic toxicity (gradual accumulation) is more common and often more dangerous than acute overdose because lithium has time to redistribute into the brain.
Epidemiology
Approximately 1 in 100 lithium-treated patients is hospitalised for toxicity each year. Risk factors include older age, renal impairment, concurrent medications that impair renal lithium clearance, and dehydration from any cause. Women and elderly patients are particularly vulnerable.
Clinical Features
Symptoms
Mild toxicity (1.5–2.0): coarse tremor (fine tremor is normal at therapeutic levels), nausea, diarrhoea, drowsiness, polyuria
Moderate toxicity (2.0–2.5): confusion, ataxia, dysarthria, muscle twitching, blurred vision, vomiting
Severe toxicity (>2.5): seizures, coma, renal failure, cardiac arrhythmias, death
Signs
Coarse tremor (at rest and with action)
Hyperreflexia and clonus
Cerebellar signs: ataxia, nystagmus, dysarthria
Reduced GCS in severe toxicity
Signs of dehydration (precipitant)
Investigations
First-line
Serum lithium level (URGENT)Take 12 hours post-dose for accuracy. >1.5 = toxicity. >2.0 = severe. Levels may continue to rise
U&EsAssess renal function (lithium is exclusively renally excreted) and electrolytes (sodium, potassium)
TFTsLithium causes hypothyroidism (long-term) — check acutely if thyroid dysfunction suspected
Second-line
ECGLithium can cause T-wave flattening/inversion, bradycardia, heart block
CalciumLithium can cause hyperparathyroidism and hypercalcaemia
Specialist
Serial lithium levelsRepeat every 6–12 hours in acute/chronic toxicity until falling
1
Mild toxicity (1.5–2.0 mmol/L)
- STOP lithium
- IV normal saline rehydration (not dextrose — saline promotes renal lithium excretion)
- Identify and treat the precipitant (dehydration, drug interaction)
- Monitor lithium levels every 6–12 hours
- Restart lithium at a lower dose once levels normalise and precipitant resolved
2
Severe toxicity (>2.0 mmol/L or symptomatic)
- STOP lithium immediately
- Aggressive IV normal saline resuscitation
- Haemodialysis if: level >2.5 mmol/L, severe symptoms (seizures, coma, renal failure), or not responding to conservative management
- Lithium rebounds after dialysis (redistributes from intracellular stores) — may need repeat dialysis
3
Prevention of toxicity
- Patient education: maintain fluid intake, avoid dehydration (D&V, hot weather, fever)
- Avoid interacting drugs: NSAIDs, ACEi, ARBs, thiazide diuretics (all reduce renal lithium clearance)
- Regular monitoring: lithium levels every 3–6 months, U&Es and TFTs every 6 months, calcium annually
- Use LITHIUM ALERT CARD and shared care protocol between GP and psychiatry
Complications
- Permanent neurological damage: Cerebellar dysfunction can be irreversible even after levels normalise
- Nephrogenic diabetes insipidus: Long-term lithium impairs ADH receptor function → polyuria and polydipsia
- Hypothyroidism: Occurs in ~20% of long-term users — treat with levothyroxine (do NOT stop lithium)
- Hyperparathyroidism: Lithium stimulates PTH secretion → hypercalcaemia
- Chronic kidney disease: Long-term use associated with tubulointerstitial nephropathy
UKMLA Exam Tips
- 1Therapeutic range 0.4–1.0 mmol/L. >1.5 = toxicity. >2.0 = severe. Measure 12 HOURS post-dose
- 2Drugs that cause lithium toxicity: NSAIDs, ACEi, ARBs, thiazide diuretics (all reduce renal lithium clearance)
- 3Dehydration from any cause (D&V, fever, hot weather) = lithium toxicity risk
- 4FINE tremor at therapeutic levels is normal. COARSE tremor = toxicity
- 5Lithium causes nephrogenic diabetes insipidus (polyuria/polydipsia), hypothyroidism, and hyperparathyroidism
- 6Haemodialysis for severe toxicity — but lithium rebounds after dialysis (may need repeat)
- 7IV SALINE not dextrose for rehydration — saline promotes renal lithium excretion
practicetest your knowledge on lithium toxicityApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — clinical pharmacology and beyond.
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