Lithium Carbonate

Lithium carbonate is the reference mood stabiliser for bipolar disorder, used for acute mania, relapse prevention and, as an add-on, resistant depression. It reduces suicide risk. It has a narrow therapeutic index and is eliminated by the kidney, so levels must be measured and toxicity can follow dehydration, kidney impairment or interacting drugs.

Classification. Mood stabiliser, alkali metal salt.

Mechanism. Not fully understood. Inhibits inositol monophosphatase and glycogen synthase kinase-3 and alters neurotransmitter signalling.

Pharmacokinetics. Completely absorbed; peak in 1 to 3 hours (4 to 5 hours for modified-release forms). Not metabolised and not protein bound; excreted unchanged by the kidney, reabsorbed in proportion to sodium. Half-life about 18 to 36 hours in normal kidney function and longer in older adults. Steady state in 5 to 7 days.

All regimens are oral with no loading dose. Prescribe a named preparation, because bioavailability differs between products.

Prophylaxis of bipolar disorder, adults.

• Start 400 mg modified-release once daily at night (200 to 300 mg in older adults or with reduced kidney function).
• Titration: measure a level 5 to 7 days after starting and after each dose change; adjust by 200 to 400 mg to the target level.
• Target serum level 0.6 to 0.8 mmol/L, taken 12 hours after the last dose. Use 0.8 to 1.0 mmol/L for higher relapse risk or partial response, and 0.4 to 0.7 mmol/L in older adults.
• Usual 400 to 1200 mg daily. Duration: long term.

Acute mania, adults (specialist use). Usually 1000 to 1800 mg daily in divided doses set by level; target 0.8 to 1.2 mmol/L, reached over 5 to 7 days.

Augmentation in resistant depression. Start 400 mg at night; target level 0.4 to 0.8 mmol/L; review at 6 weeks.

Dose limits. Estimated glomerular filtration rate 30 to 59 mL/min: reduce the dose and check levels every 1 to 2 months; under 30 mL/min: avoid. Haemodialysis: give after dialysis, with specialist advice. Liver impairment: no adjustment.

Contraindications. Severe kidney impairment, acute renal failure, untreated hypothyroidism, Addison disease, severe dehydration, low sodium states, Brugada syndrome, severe cardiovascular disease, hypersensitivity.

Serious adverse effects. Boxed-warning-level lithium toxicity (coarse tremor, vomiting, diarrhoea, ataxia, dysarthria, confusion, seizures, coma). Chronic kidney disease, nephrogenic diabetes insipidus, hypothyroidism, hyperparathyroidism with hypercalcaemia, QT prolongation and sinus node dysfunction, serotonin syndrome in combination, teratogenicity.

Common adverse effects. Fine tremor, polyuria and thirst, weight gain, nausea, diarrhoea, metallic taste, leucocytosis, acne or psoriasis worsening, cognitive dulling.

Interactions. Thiazide diuretics (raise levels by 25 to 40%), ACE inhibitors and angiotensin receptor blockers (about 35%), NSAIDs (20 to 60%) and metronidazole raise levels and are avoided or monitored closely. Loop diuretics have a smaller effect. Haloperidol, carbamazepine, diltiazem and verapamil can cause neurotoxicity at normal levels. Serotonergic drugs raise serotonin syndrome risk. Theophylline, acetazolamide, sodium bicarbonate and caffeine lower levels.

Common prescribing errors. Prescribing a different brand without rechecking levels; adding an NSAID or ACE inhibitor without a level; missing kidney decline; taking a level at the wrong time; failing to stop it during vomiting or diarrhoea.

Special groups.

• Pregnancy: avoid in the first trimester if possible because of an increased risk of cardiac malformations; if essential, use the lowest effective dose in divided doses, check levels monthly then weekly in the last month, and stop at the onset of labour.
• Breastfeeding: infant levels reach about one quarter to one half of the maternal level; usually avoided; if used, monitor the infant’s level, thyroid and kidney function.
• Children: specialist use only; not advised in under 12 years.
• Older adults: lower targets (0.4 to 0.7 mmol/L); higher toxicity at normal levels.
• Kidney impairment: reduce dose, monitor often; avoid if eGFR is under 30 mL/min.
• Liver impairment: no adjustment.
• Regional: hot climate, dehydration, diarrhoeal illness and over-the-counter NSAIDs are common triggers for toxicity; give written sick-day advice to stop lithium during vomiting, diarrhoea or poor fluid intake and to seek a level.

Formulations. Modified-release tablets 200 mg and 400 mg; immediate-release capsules or tablets 250 mg and 300 mg; oral liquid in some regions. Strengths of carbonate and citrate are not equivalent. Swallow modified-release tablets whole with fluids, in the evening.

Baseline. eGFR and electrolytes, calcium, thyroid function, full blood count, ECG if over 40 years or cardiac disease, pregnancy test, weight, BMI.

Monitoring. Serum lithium 12 hours after the last dose: 5 to 7 days after starting or any change, then every 3 months for the first year, then every 6 months (every 3 months in older adults or with kidney disease or interacting drugs).

eGFR, electrolytes, calcium and thyroid function every 6 months. Weight annually.

Review urgently if level is over 1.0 mmol/L or symptoms of toxicity appear. A level over 1.5 mmol/L needs withholding the drug; over 2.0 mmol/L with neurological signs, or any level with kidney impairment, needs urgent hospital assessment for haemodialysis.

Stopping. Reduce slowly over at least 4 weeks, ideally up to 3 months; abrupt stopping carries a high risk of relapse.

Referral and escalation. Prescribing is restricted to psychiatry or under shared care. Toxicity symptoms, level over 1.5 mmol/L, or falling eGFR needs same-day assessment.