Mood Stabilisers and Lithium
On this page
Direct answer
Lithium remains the prototype mood stabiliser: a simple ion with a narrow therapeutic index of 0.6-1.2 mEq/L, excreted entirely by the kidney, whose clearance falls — and toxicity rises — with NSAIDs, thiazides, ACE inhibitors and salt restriction. Around it stand the alternatives: valproate for mania, carbamazepine where lithium fails (after HLA-B*15:02 screening in Asian patients), and lamotrigine, which protects the depressive pole. Monitoring defines the whole class — lithium levels, thyroid function, renal function and calcium; valproate liver function and teratogenicity; lamotrigine rash vigilance — and every agent demands pre-conception planning because all four are teratogenic concerns, valproate worst of all.
What you must remember
- Lithium mechanism: inhibits inositol monophosphatase (depleting the IP3 second-messenger pool) and GSK-3beta — quotable in every viva.
- Therapeutic window: 0.6-1.2 mEq/L (12-hour trough); coarse tremor gives way to ataxia, confusion and seizures as levels climb; severe toxicity needs haemodialysis.
- Clearance falls with: NSAIDs, thiazides, ACE inhibitors, dehydration and low-salt diets — a stable patient can become toxic on an unchanged dose during gastroenteritis.
- Clearance rises with: theophylline, caffeine, sodium loading and pregnancy — relapse from subtherapeutic levels.
- Chronic complications: hypothyroidism with goitre, nephrogenic diabetes insipidus (paradoxically treated with a thiazide plus amiloride), hypercalcaemia, weight gain and acne.
- Teratogenicity: lithium associates with Ebstein anomaly; valproate carries the highest neural tube and neurodevelopmental risk and is avoided in women who may conceive.
- Lamotrigine rules: best for bipolar depression; titrate slowly to prevent Stevens-Johnson syndrome, and halve the dose when valproate doubles its half-life.
A monitoring schedule that prevents disasters
Baseline before the first lithium tablet: creatinine and eGFR, TSH, calcium, pregnancy test, weight. Levels five to seven days after any dose change, drawn twelve hours after the last dose. Thereafter thyroid and renal function every six to twelve months, more often with intercurrent illness. The teaching case writes itself: a woman stable on 900 mg for years is admitted with vomiting and diarrhoea, given an NSAID for body ache and a thiazide for ankle swelling, and arrives confused with a coarse tremor — lithium toxicity at an unchanged dose, because sodium and water loss shrank her clearance. The response is hold lithium, restore volume and salt, check a level, and resume at lower dose once stable. The same logic makes pre-surgical and pre-delivery periods high-risk: nothing about the dose changed, everything about the physiology did.
Carbamazepine adds its own drill: screen HLA-B*15:02 before the first dose in patients of Asian ancestry, watch for rash in the first eight weeks, monitor sodium for hyponatraemia and remember autoinduction lowering its own levels by week three.
Prescribing in the Indian context
Lithium carbonate sits on the NLEM, but Indian practice leans harder on valproate — cheaper tablets, no blood-level logistics, and patchy monitoring infrastructure make the trade understandable and examinable. The costs surface in young women: valproate-related weight gain, PCOS features and the teratogenic burden that makes pre-conception counselling non-negotiable. HLA-B*15:02 screening matters here because the allele is prevalent in several Indian populations, particularly in the north-east, before carbamazepine for any indication. Lithium toxicity and valproate hepatotoxicity both belong on PvPI report forms.
Frequently asked questions
What is lithium's therapeutic range and how is it sampled?
0.6-1.2 mEq/L, measured as a 12-hour post-dose trough, rechecked five to seven days after any dose change or interacting illness.
Why do thiazides paradoxically treat lithium-induced diabetes insipidus?
Thiazides reduce lithium delivery to the distal nephron by inducing mild proximal volume-sodium retention, blunting the drug's concentration at its site of injury.
Which mood stabiliser suits bipolar depression best?
Quetiapine and lamotrigine carry the strongest evidence; antidepressant monotherapy is avoided because it risks switching and is ineffective for the cycle.
Which congenital anomaly defines lithium exposure?
Ebstein anomaly — apical displacement of the tricuspid valve; risk is low but counselling and detailed anomaly scanning are standard.
Why screen HLA-B*15:02 before carbamazepine?
Carriage predicts Stevens-Johnson syndrome and toxic epidermal necrolysis with high probability in East and South-East Asian and several Indian populations.