Formulary
Lithium: Uses, Dosing, Side Effects and Indian Brand Names
Lithium is the gold standard mood stabiliser for bipolar disorder and the only psychiatric drug proven to reduce suicide risk. It has an extremely narrow therapeutic index requiring regular serum level monitoring and can cause nephrogenic diabetes insipidus, hypothyroidism, and Ebstein anomaly.
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Lithium: Uses, Dosing, Side Effects and Indian Brand Names
Lithium is the gold standard mood stabiliser for bipolar disorder and the only psychiatric drug proven to reduce suicide risk. It has an extremely narrow therapeutic index requiring regular serum level monitoring and can cause nephrogenic diabetes insipidus, hypothyroidism, and Ebstein anomaly.
NEET PG High-Yield: Lithium is the ONLY drug proven to reduce suicide risk in bipolar disorder. Ebstein anomaly (first-trimester teratogenicity) is the most tested association. Nephrogenic DI (not central) is the most common renal side effect. Narrow therapeutic index: 0.6-1.2 mEq/L. Thiazides precipitate lithium toxicity by increasing proximal tubular reabsorption of lithium alongside sodium.
Clinical overview
Lithium is the gold standard mood stabiliser and remains the first-line drug for the prophylaxis of bipolar affective disorder (both manic and depressive episodes). It was introduced by John Cade in 1949 and is the only mood stabiliser proven to reduce suicide risk in bipolar disorder -- a unique therapeutic property. Lithium has the narrowest therapeutic index of any commonly used psychiatric medication (therapeutic range: 0.6-1.2 mEq/L; toxicity begins at >1.5 mEq/L), making regular serum level monitoring mandatory. It is primarily excreted by the kidneys (80% reabsorbed in the proximal tubule alongside sodium), and any condition or drug that reduces sodium balance (dehydration, low-salt diet, thiazide diuretics, NSAIDs, ACE inhibitors) can precipitate lithium toxicity. The classic side-effect triad of lithium includes nephrogenic diabetes insipidus (polyuria and polydipsia, due to downregulation of aquaporin-2 channels), hypothyroidism (inhibition of thyroid hormone synthesis and release), and tremor. Lithium is absolutely contraindicated in the first trimester of pregnancy due to the risk of Ebstein anomaly (downward displacement of the tricuspid valve). In Indian psychiatry, lithium remains widely used due to its proven efficacy, low cost, and decades of clinical experience, though monitoring infrastructure is limited in rural areas.
Pharmacological class
Lithium belongs to the Mood stabiliser (alkali metal ion) class. Lithium's mechanism is complex and not fully elucidated. It inhibits inositol monophosphatase, depleting inositol stores and reducing IP3/DAG second messenger signalling (inositol depletion hypothesis). It also inhibits glycogen synthase kinase-3beta (GSK-3beta), modulating Wnt signalling and neuroprotection. Additionally, lithium modulates neurotransmitter release, increases serotonin synthesis, and affects circadian rhythm regulation through effects on the molecular clock.
Indian brand names and formulations
Available as: Licab (Sun Pharma), Lithosun (Sun Pharma), Intalith CR (Intas Pharmaceuticals), Lithoril (Torrent Pharmaceuticals).
Tablets (300 mg), Controlled-release tablets (400 mg CR), Capsules (150 mg, 300 mg), Oral liquid (rare in India)
Regulatory status
Lithium is classified under Schedule H in India under the Drugs and Cosmetics Act, 1940. Schedule H prescription drug. Requires mandatory therapeutic drug monitoring (serum lithium levels every 1-3 months). Baseline and periodic thyroid function, renal function, and ECG monitoring are essential.
Indications
- Bipolar affective disorder -- prophylaxis (first-line) and acute mania (second-line due to slow onset)
- Suicide prevention in mood disorders (unique indication)
- Schizoaffective disorder (augmentation)
- Treatment-resistant depression (augmentation of antidepressants)
- Cluster headache prophylaxis
- Neutropenia (drug-induced or cyclical -- lithium stimulates granulopoiesis)
Dosing
Adults: Start 300 mg BD-TDS, titrate based on serum levels. Target serum level: 0.6-1.0 mEq/L for prophylaxis, 0.8-1.2 mEq/L for acute mania. Measure trough levels 12 hours after last dose, 5-7 days after dose change (to reach steady state). Elderly: lower doses, target 0.4-0.8 mEq/L. Monitor serum lithium, TSH, creatinine, eGFR every 3-6 months. Adequate sodium and water intake must be maintained. Toxic level: >1.5 mEq/L; life-threatening: >2.5 mEq/L.
Contraindications
- First trimester of pregnancy (Ebstein anomaly risk)
- Severe renal insufficiency
- Addison's disease (sodium-depleted state)
- Brugada syndrome
- Significant cardiovascular disease with sodium restriction
- Conditions causing severe sodium depletion (increases lithium reabsorption)
Adverse effects
- Nephrogenic diabetes insipidus (polyuria, polydipsia -- most common; due to AQP2 downregulation; treated with amiloride)
- Hypothyroidism (can develop goitre; monitor TSH; treat with levothyroxine without stopping lithium)
- Fine tremor (common, dose-related; treated with propranolol)
- Weight gain
- GI disturbance (nausea, diarrhoea)
- Cognitive dulling (complaints of mental slowness)
- Acne and psoriasis exacerbation
- Benign leucocytosis (neutrophilia)
- ECG changes (T-wave flattening/inversion)
- Chronic nephropathy (interstitial nephritis with long-term use)
- Toxicity signs: coarse tremor, ataxia, dysarthria, vomiting, seizures, coma
Drug interactions
- Thiazide diuretics -- reduce sodium, increase lithium reabsorption, precipitate toxicity
- NSAIDs (especially indomethacin) -- reduce renal lithium clearance by 25-50%
- ACE inhibitors and ARBs -- reduce lithium excretion
- Metronidazole -- reduces lithium clearance
- Loop diuretics -- less dangerous than thiazides but still increase lithium levels
- Carbamazepine -- additive neurotoxicity without changing lithium levels
- Haloperidol -- rare NMS-like encephalopathic syndrome
Pregnancy and lactation
Category D. Contraindicated in the first trimester due to risk of Ebstein anomaly (downward displacement of the tricuspid valve into the right ventricle; incidence approximately 1 in 1000 with lithium exposure vs 1 in 20,000 in general population). If lithium is essential, fetal echocardiography at 16-20 weeks is recommended. Lithium levels fluctuate during pregnancy due to increased renal clearance and must be monitored more frequently. Dose reduction is needed in the third trimester to prevent neonatal toxicity.
Exam-style clinical scenario
A 35-year-old woman on lithium for bipolar disorder presents with increased urination (4-5 litres/day), excessive thirst, and a serum lithium level of 0.8 mEq/L. Her urine osmolality is 180 mOsm/kg and does not concentrate after desmopressin (DDAVP) administration. What is the diagnosis? Answer: Nephrogenic diabetes insipidus (NDI) caused by lithium. Lithium downregulates aquaporin-2 (AQP2) water channels in the renal collecting duct, making the kidney resistant to ADH. The lack of response to DDAVP confirms nephrogenic (not central) DI. Management: ensure adequate hydration, consider dose reduction, and add amiloride (blocks lithium entry into collecting duct cells via ENaC channels). Thiazide diuretics are paradoxically used in NDI but must be used with extreme caution with lithium due to toxicity risk.
Cost in India
INR 20-50 per strip of 10 tablets (300 mg); CR formulation: INR 40-80 per strip
Clinical governance
Author: MedNext Editorial Team. Clinical reviewer: Awaiting clinical review. Jurisdiction: India (Drugs and Cosmetics Act, 1940). Sources: CIMS India, Indian Pharmacopoeia. Publication state: Awaiting clinical review. Correction: Report errors at support@mednext.academy.
Frequently Asked Questions
Why do thiazide diuretics precipitate lithium toxicity?
Thiazide diuretics act on the distal convoluted tubule to block sodium reabsorption, causing natriuresis and volume depletion. The resulting sodium deficit triggers compensatory sodium (and lithium) reabsorption in the proximal tubule, where lithium is handled similarly to sodium. This increases lithium reabsorption and raises serum levels, potentially to toxic concentrations. Loop diuretics are somewhat safer as they cause less compensatory proximal reabsorption.
How does lithium cause hypothyroidism?
Lithium concentrates in the thyroid gland and inhibits multiple steps: iodine organification, coupling of iodotyrosines, thyroid hormone secretion, and peripheral deiodination of T4 to T3. The net effect is reduced thyroid hormone levels, compensatory TSH elevation, and potential goitre development. This occurs in 5-35% of patients. Importantly, lithium-induced hypothyroidism is treated with levothyroxine supplementation WITHOUT discontinuing lithium, as the mood-stabilising benefit typically outweighs the thyroid effect.
What is Ebstein anomaly and why is it associated with lithium?
Ebstein anomaly is a congenital cardiac malformation where the tricuspid valve is displaced downward into the right ventricle, causing tricuspid regurgitation and right heart failure. First-trimester lithium exposure increases the risk approximately 20-fold (from 1:20,000 to approximately 1:1,000). The mechanism may involve lithium's inhibition of GSK-3beta during cardiac morphogenesis. Despite this, the absolute risk is small (0.1%), and guidelines recommend shared decision-making with fetal echocardiography if lithium is continued.
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