Schedule H

Oral

Formulation Type Available Strengths

Immediate-release tablets 300 mg, 400 mg

Controlled-release (CR) tablets 300 mg, 400 mg (brand-specific availability)

Note: Injectable formulations are NOT AVAILABLE in India.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Bipolar Disorder — Acute Mania (Adults)

Parameter Recommendation

Starting dose 600–900 mg/day in 2–3 divided doses

Titration Increase by 300 mg every 3–5 days guided by serum lithium levels and tolerability

Usual maintenance dose 900–1200 mg/day in divided doses

Maximum dose 1800 mg/day (only with therapeutic drug monitoring)

Target serum lithium: 0.8–1.0 mmol/L (acute phase)

Clinical notes:

• Antimanic effect may take 7–10 days to manifest

• Consider short-term adjunctive antipsychotic or benzodiazepine for immediate symptom control

• Always obtain serum lithium level 12 hours post-dose (trough level), 5–7 days after any dose change

1. Bipolar Disorder — Maintenance/Prophylaxis (Adults)

Parameter Recommendation

Starting dose Continue from acute phase dosing or initiate at 600 mg/day

Titration Adjust based on serum lithium levels

Usual maintenance dose 600–1200 mg/day in divided doses

Maximum dose 1800 mg/day (rarely required)

Target serum lithium: 0.6–0.8 mmol/L (maintenance)

Clinical notes:

• Long-term therapy requires regular monitoring of renal and thyroid function

• Controlled-release formulations may improve tolerability and adherence

• Avoid abrupt discontinuation — risk of relapse or rebound mania

1. Augmentation in Treatment-Resistant Major Depressive Disorder (Adults)

Parameter Recommendation

Starting dose 300 mg once daily

Titration Increase by 300 mg every 5–7 days based on response and serum levels

Usual maintenance dose 600–900 mg/day

Maximum dose 1200 mg/day

Target serum lithium: 0.4–0.6 mmol/L (lower than for bipolar disorder)

Clinical notes:

• Specialist-initiated therapy only

• Used as augmentation to antidepressants in treatment-resistant depression

• Response typically assessed over 4–6 weeks

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes Evidence

Schizoaffective disorder As per bipolar dosing; target serum level 0.6–1.0 mmol/L Long-term OFF-LABEL; Specialist only; used with antipsychotics Indian psychiatric centre protocols; case series

Cluster headache prophylaxis 600–900 mg/day in divided doses Specialist-guided duration OFF-LABEL; Specialist only International RCTs; limited Indian data

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Bipolar Disorder — Acute Mania and Maintenance (Age ≥12 years)

Body Weight Starting Dose Titration Target Serum Level Maximum Dose

20–30 kg 300 mg/day in divided doses Increase by 300 mg every 5–7 days 0.6–1.0 mmol/L 900 mg/day

30–50 kg 300 mg twice daily Increase by 300 mg every 5–7 days 0.6–1.0 mmol/L 1200 mg/day

50 kg 600 mg/day in divided doses (adult-like dosing) Increase by 300 mg every 5–7 days 0.6–1.0 mmol/L 1500 mg/day

Safety Monitoring in Paediatrics:

• Serum lithium level (12-hour trough) — 5–7 days after each dose change

• Renal function (creatinine, eGFR) at baseline and every 3–6 months

• Thyroid function (TSH) at baseline and every 6 months

• Weight and growth parameters at each visit

• Monitor for signs of toxicity at each visit

Secondary Indications — Paediatric (Off-label)

Not applicable. No documented off-label paediatric indications in Indian sources.

Important statements:

• Not recommended below 12 years of age except in exceptional circumstances under tertiary psychiatric care

• Paediatric use requires child and adolescent psychiatrist supervision

• Family counselling regarding signs of toxicity is mandatory

60 No dose adjustment; monitor levels regularly

30–60 Specialist only; reduce starting dose by 25–50%; increase monitoring frequency to weekly initially

<30 Avoid use; consider only if no alternatives under very close specialist supervision

Haemodialysis Lithium is dialyzable; if used, administer dose post-dialysis; consult nephrologist

Critical considerations:

• Lithium is almost exclusively renally excreted

• Avoid dehydration — may precipitate toxicity

• Any condition causing sodium/fluid loss (diarrhoea, vomiting, fever) increases toxicity risk

• Exercise extreme caution with concomitant diuretics, ACE inhibitors, or ARBs

Note: Lithium is not hepatically metabolised — safe in hepatic impairment from a pharmacokinetic standpoint.

• Known hypersensitivity to lithium

• Severe renal impairment (eGFR <30 mL/min) or renal failure

• Significant dehydration or severe sodium depletion

• Untreated Addison's disease

• Brugada syndrome or significant cardiac conduction abnormalities

• First trimester of pregnancy (teratogenicity risk — Ebstein's anomaly)

• Concomitant use with thiazide diuretics without close monitoring capability

• Narrow therapeutic index — requires meticulous serum level monitoring

• Pre-existing thyroid disorders — lithium may cause or worsen hypothyroidism

• Cardiovascular disease — ECG changes, risk of arrhythmias

• Conditions causing fluid/electrolyte shifts (vomiting, diarrhoea, excessive sweating)

• Concurrent nephrotoxic drugs or sodium-altering medications (NSAIDs, ACE inhibitors, ARBs, diuretics)

• Psoriasis — may exacerbate

• Myasthenia gravis

• Elderly patients — increased sensitivity, reduced renal reserve

• Surgery/anaesthesia — may need temporary dose reduction or cessation

• Patients with cognitive impairment who may not report early toxicity symptoms

Parameter Recommendation

Overall safety Teratogenic risk — particularly first trimester; associated with Ebstein's anomaly (cardiac malformation)

Preferred alternative Antipsychotics (olanzapine, haloperidol) for acute mania; lamotrigine for maintenance if appropriate

When may be used Only if essential, no effective alternatives, and benefit clearly outweighs risk; shared decision with psychiatrist and obstetrician

What to monitor Fetal echocardiography in first trimester; maternal serum lithium levels throughout (increased renal clearance in pregnancy); growth scans; avoid near delivery due to rapid volume/clearance changes postpartum

Parameter Recommendation

Compatibility Not recommended — lithium passes into breast milk at significant levels

Preferred alternative Valproate (with caution), lamotrigine, or antipsychotics depending on clinical situation

Drug levels in milk High (30–50% of maternal serum level)

Infant monitoring If used despite recommendations: monitor infant serum lithium, TSH, renal function, hydration status, feeding adequacy

Note: Specialist-only decision if breastfeeding while on lithium is considered.

Parameter Recommendation

Starting dose 150–300 mg/day

Titration Very slow — every 1–2 weeks based on serum levels

Target serum level Lower end of therapeutic range (0.4–0.6 mmol/L for maintenance)

Special risks Reduced renal clearance — increased accumulation risk; increased neurotoxicity sensitivity; dehydration; falls; confusion; drug interactions with common medications (diuretics, antihypertensives)

Additional considerations More frequent monitoring of serum levels, renal function, and electrolytes; ensure adequate hydration; baseline ECG recommended

Interacting Drug Effect / Risk Recommendation

Thiazide diuretics (hydrochlorothiazide, chlorthalidone) Increased lithium levels via enhanced renal reabsorption — high toxicity risk Avoid combination; if unavoidable, reduce lithium dose by 50% and monitor levels closely

ACE inhibitors (enalapril, ramipril, lisinopril) Reduced lithium clearance — increased levels and toxicity risk Avoid or monitor very closely; check lithium level within 5–7 days of initiation

ARBs (losartan, telmisartan) Similar mechanism to ACE inhibitors — increased lithium concentration Avoid or monitor closely; check levels frequently

NSAIDs (ibuprofen, diclofenac, naproxen) Reduced lithium clearance — may precipitate toxicity Avoid chronic NSAID use; short-term use requires close monitoring

Metronidazole Reduced lithium clearance Monitor lithium levels if combination necessary

Interacting Drug Effect / Risk Recommendation

SSRIs (fluoxetine, sertraline) Possible serotonin toxicity; additive CNS effects Use with caution; monitor for serotonin syndrome symptoms

Antipsychotics (haloperidol, risperidone) Additive neurotoxicity (tremor, confusion, EPS) Monitor closely; reduce doses if neurotoxicity appears

Carbamazepine Additive neurotoxicity; risk of hyponatraemia Monitor sodium and neurological status

Topiramate Increased CNS side effects; rare encephalopathy Use with caution; monitor for confusion, cognitive effects

Loop diuretics (furosemide) Variable effect on lithium levels Monitor lithium levels; less risky than thiazides

Theophylline/aminophylline Increased lithium clearance — reduced efficacy May require increased lithium dose; monitor levels

Caffeine (high intake) Increased lithium clearance Counsel patient to maintain consistent caffeine intake

Sodium-containing antacids May lower lithium levels Monitor levels if significant antacid use

• Fine postural tremor

• Polyuria and polydipsia (nephrogenic diabetes insipidus)

• Weight gain

• Nausea, diarrhoea, abdominal discomfort

• Dry mouth, metallic taste

• Hypothyroidism (long-term use)

• Oedema

• Acneiform rash

• Hair thinning

• Cognitive dulling ("mental fog")

Adverse Effect Notes

Lithium toxicity Coarse tremor, ataxia, dysarthria, confusion, seizures, coma — requires immediate discontinuation and hospitalisation

Nephrogenic diabetes insipidus May persist after discontinuation; monitor for polyuria

Chronic renal impairment / CKD Long-term use may cause interstitial nephritis; monitor renal function

Hypothyroidism / Goitre Common with prolonged use; may require thyroid supplementation

Cardiac arrhythmias T-wave flattening, sinus node dysfunction — especially in elderly or cardiac patients

Serotonin syndrome When combined with serotonergic drugs — agitation, hyperthermia, tremor

Ebstein's anomaly Fetal cardiac malformation if used in first trimester

All serious adverse effects require dose interruption or hospitalisation.

Target serum lithium levels Acute mania: 0.8–1.0 mmol/L; Maintenance: 0.6–0.8 mmol/L; Depression augmentation: 0.4–0.6 mmol/L

Long-term Serum lithium every 3 months (stable patients); renal function and electrolytes every 3–6 months; TSH every 6–12 months; body weight periodically; ECG annually in elderly

Additional monitoring triggers:

• Any intercurrent illness with fluid loss

• Addition or change of interacting medications

• Signs/symptoms suggestive of toxicity

• Licab (Torrent)

• Lithosun (Sun Pharma)

• Intalith CR (Intas) — controlled-release

• Licab CR (Torrent) — controlled-release

• Eskalith (GSK — limited availability)

• Lilithium (Mankind)

• Multiple generic brands available

Note: Confirm whether immediate-release or controlled-release formulation — not interchangeable without dose adjustment.

Notes:

• Listed under NLEM 2022 — essential medicine; may be available through government supply

• Private market prices vary by brand

• CR formulations generally priced slightly higher

1. Timing of serum lithium is critical: Always measure 12-hour trough level (12 hours post-dose); incorrect timing leads to misinterpretation

1. Recheck levels with any interacting drug: Any new medication affecting sodium balance or renal function (diuretics, ACE inhibitors, NSAIDs) mandates repeat lithium level within 5–7 days

1. Patient education is essential: Counsel patients and caregivers on early signs of toxicity (tremor, nausea, diarrhoea, confusion, unsteady gait) and importance of maintaining hydration

1. Avoid abrupt discontinuation: Taper gradually to prevent rebound mania or depressive relapse

1. Long-term monitoring is non-negotiable: Annual thyroid and renal function assessment is mandatory for all patients on chronic lithium therapy

1. Elderly require lower targets: Use lower serum lithium targets (0.4–0.6 mmol/L) and more frequent monitoring due to reduced renal reserve and increased sensitivity

1. IR vs CR formulations matter: Controlled-release formulations may reduce GI side effects and peak-related adverse effects but are not interchangeable without dose adjustment

lithium; mood-stabiliser; bipolar-disorder; mania; nephrotoxic-risk; narrow-therapeutic-index; pregnancy-contraindicated; thyroid-monitoring; NLEM-India; psychiatry

RxIndia v1.0 — 29 Apr 2025

• CDSCO-approved prescribing information

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• NLEM 2022

• API Textbook of Medicine

• NIMHANS/AIIMS Psychiatry protocols

• ICMR Guidelines for Bipolar Disorder

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• WHO Essential Medicines List (supportive reference for paediatric use)