Key Facts

Lithium remains the most effective mood stabiliser and the only psychotropic with proven anti-suicidal properties. Its use requires careful monitoring due to its narrow therapeutic index.

Epidemiology

Approximately 40,000-50,000 people take lithium in the UK. It is primarily prescribed for bipolar disorder but also for augmentation in treatment-resistant depression.

Aetiology

Mechanism of action (multiple):

• Inhibits inositol monophosphatase → depletes inositol → modulates intracellular signalling
• Inhibits GSK-3β → neuroprotective effects, promotes neuroplasticity
• Modulates dopamine, serotonin, and glutamate neurotransmission
• Enhances GABA transmission
• Anti-inflammatory and neuroprotective properties (increases grey matter volume)

Pathophysiology

Lithium toxicity:

• Lithium is renally excreted (filtered and ~80% reabsorbed in PCT — competes with sodium)
• Anything reducing renal clearance raises lithium levels: Dehydration, renal impairment, NSAIDs, ACEi, thiazides
• Sodium depletion → increased lithium reabsorption (proximal tubule) → toxicity
• Chronic toxicity affects CNS, kidneys, and thyroid

Therapeutic Effects

• Mood stabilisation — reduces frequency and severity of manic and depressive episodes
• Anti-suicidal effect — independent of mood stabilisation
• Augmentation of antidepressants in TRD
• May slow cognitive decline in Alzheimer's (emerging evidence)

Common Side Effects

• Fine tremor (postural) — dose-related, common
• Polyuria and polydipsia — nephrogenic diabetes insipidus (ADH resistance)
• Weight gain — significant in many patients
• GI symptoms — nausea, diarrhoea (especially at initiation)
• Hypothyroidism — ~20-30%; clinical or subclinical
• Cognitive dulling — subjective in many patients
• Acne, psoriasis exacerbation

Lithium Toxicity (Level >1.5 mmol/L)

• Mild (1.5-2.0): Coarse tremor, nausea, vomiting, diarrhoea, blurred vision
• Moderate (2.0-2.5): Ataxia, dysarthria, confusion, muscle twitching, hyperreflexia
• Severe (>2.5): Seizures, coma, cardiac arrhythmias, renal failure — MEDICAL EMERGENCY

Red Flags

• GI symptoms (nausea/vomiting/diarrhoea) in a patient on lithium — check level urgently (toxicity vs causing dehydration → toxicity)
• Any intercurrent illness with dehydration — hold lithium and check level
• New NSAID or ACEi prescribed — check lithium level
• Pregnancy — specialist review immediately

Monitoring Schedule

• Pre-treatment: U&Es, eGFR, TFTs, calcium, FBC, ECG, pregnancy test (if relevant), BMI
• After starting/dose change: Lithium level weekly until stable (trough, 12 hours post-dose)
• Stable treatment: Lithium level every 3 months, U&Es/eGFR every 6 months, TFTs every 6 months, calcium annually

Urgent Tests

• Lithium level: If any symptoms of toxicity, intercurrent illness, dehydration, new interacting medication
• U&Es: Assess renal function
• ECG: If cardiac symptoms or severe toxicity

Starting Lithium

• Lithium carbonate (Priadel, Camcolit) — brands are NOT interchangeable due to different bioavailability
• Start at 400mg ON; titrate based on levels (12-hour trough)
• Target: 0.6-0.8 mmol/L (maintenance); 0.8-1.0 mmol/L (acute mania); 0.4-0.8 mmol/L (augmentation)
• Lithium card: All patients should carry a lithium alert card
• Patient education: Signs of toxicity, avoid dehydration, interactions

Managing Toxicity

• Mild-moderate: Stop lithium, IV 0.9% saline resuscitation, monitor levels and U&Es, supportive care
• Severe (>2.5 or symptomatic severe): ICU admission, aggressive IV fluids, consider haemodialysis (level >3.0 or renal failure or severe symptoms)
• Avoid sodium-restricted fluids — sodium depletion worsens lithium toxicity
• Resume lithium at lower dose once resolved (if appropriate) or switch to alternative mood stabiliser

Drug Interactions to Avoid

• NSAIDs: Reduce lithium clearance → toxicity (paracetamol is safe)
• ACE inhibitors/ARBs: Reduce lithium clearance
• Thiazide diuretics: Reduce lithium clearance (loop diuretics are safer if diuretic needed)
• Metronidazole: Reduces lithium clearance

Referral Criteria

• Lithium initiation — specialist (psychiatrist)
• Shared care with GP for ongoing monitoring
• Lithium toxicity — emergency medical admission
• Pregnancy on lithium — perinatal mental health team and obstetrics
• Renal impairment developing — nephrology

• Bipolar disorder: Lithium reduces relapse by ~40% and suicide by ~60%
• Renal effects: ~10-20% develop some renal impairment after 15+ years; end-stage renal failure is rare (~1%)
• Thyroid: Hypothyroidism in ~20-30% (manage with levothyroxine; lithium usually continued)
• Hyperparathyroidism: ~10-15% develop elevated calcium — monitor annually
• Pregnancy: Ebstein's anomaly risk ~1% (vs baseline 0.05%); detailed cardiac scanning recommended
• Cognitive effects: Subjective dulling common; objective deficits usually modest
• Discontinuation: Abrupt withdrawal increases relapse risk — always taper slowly over ≥4 weeks

Lithium Monitoring Summary

Drugs That Increase Lithium Levels