SN4 SHORT NOTE 5M ★ High-yield

Describe lithium with its adverse effects, interactions and monitoring. Add a note on other mood stabilisers.

Pharmacology · 2nd Professional — Para-Clinical

Lithium

Lithium is the prototype mood stabiliser, effective in the treatment and prophylaxis of bipolar disorder, and the only psychotropic shown to reduce suicide.

Mechanism — not fully known; inhibits inositol monophosphatase, depleting the phosphatidylinositol second messenger system, and inhibits glycogen synthase kinase-3
Pharmacokinetics — a small ion, not protein-bound, not metabolised, excreted entirely by the kidney; handled like sodium, so sodium depletion causes lithium retention
Very narrow therapeutic index — therapeutic range 0.6 to 1.0 mmol/L; toxicity above 1.5 mmol/L

Adverse Effects

Timing	Effects
Early and common	Fine tremor, nausea, diarrhoea, metallic taste, polyuria and polydipsia, weight gain
Long-term	Hypothyroidism and goitre (lithium blocks hormone release); nephrogenic diabetes insipidus; chronic interstitial nephritis; hyperparathyroidism and hypercalcaemia
Toxicity (above 1.5 mmol/L)	Coarse tremor, vomiting and diarrhoea, ataxia, slurred speech, drowsiness, muscle twitching and hyperreflexia; then confusion, convulsions, coma, arrhythmia and renal failure
Teratogenicity	Ebstein anomaly of the tricuspid valve with first-trimester exposure

CLINICAL PEARL

Anything that depletes sodium raises lithium. The kidney reabsorbs lithium wherever it reabsorbs sodium, so dehydration, vomiting, diarrhoea, a low-salt diet, hot weather, a thiazide, an NSAID or an ACE inhibitor all cause it to accumulate. A stable patient can become toxic from a bout of gastroenteritis or a new prescription for back pain — which is why every patient must be told this explicitly.

Interactions and Monitoring

Drugs raising lithium levels — thiazides, NSAIDs, ACE inhibitors and ARBs, metronidazole, tetracyclines
Drugs lowering levels — theophylline, sodium bicarbonate, acetazolamide, osmotic diuretics
Monitoring — lithium level 12 hours after the dose, weekly until stable then every 3 months; renal and thyroid function every 6 months; calcium periodically
Management of toxicity — stop lithium, give saline to restore volume and promote excretion, and haemodialysis for severe toxicity — lithium is ideal for dialysis, having a small volume of distribution, no protein binding and low molecular weight

Other Mood Stabilisers

Drug	Place in therapy	Chief cautions
Sodium valproate	Effective in acute mania and in prophylaxis	Teratogenic — must not be used in women of childbearing potential
Lamotrigine	Best for the depressive pole of bipolar disorder	Rash and Stevens–Johnson syndrome — the dose must be increased very slowly, and halved if valproate is co-prescribed
Carbamazepine	Second-line prophylaxis	Enzyme induction; hyponatraemia
Atypical antipsychotics	Olanzapine, quetiapine, risperidone, aripiprazole — effective in acute mania and increasingly used for maintenance	Metabolic effects

Applied Aspects

Give every patient clear written instructions — maintain fluid and salt intake, report vomiting, diarrhoea or fever promptly, and check before taking any new medicine including over-the-counter painkillers
NSAIDs bought over the counter are a common precipitant of lithium toxicity, and patients do not think of them as drugs
Never stop lithium abruptly — rebound mania and a high risk of relapse follow; taper over weeks
Check a pregnancy test and counsel before starting in any woman of childbearing age; if lithium is essential in pregnancy, fetal echocardiography is arranged
Reliable laboratory access is the limiting factor for lithium use in parts of India; where levels cannot be measured safely, valproate in men or an atypical antipsychotic may be the more practical choice

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