Lithium
Mood stabilizer for bipolar disorder, mania and treatment-resistant depression
Lithium is one of the oldest and most effective mood stabilizers, included on the WHO Model List of Essential Medicines. It is the first-line treatment for bipolar disorder, preventing manic and depressive episodes and reducing the risk of suicide. Lithium has a narrow therapeutic index, meaning the difference between an effective dose and a toxic dose is small, so regular blood monitoring is essential throughout treatment.
Quick Facts
Key Takeaways
- Lithium is the gold standard mood stabilizer for bipolar disorder, effective in treating and preventing both manic and depressive episodes with over 60 years of clinical evidence.
- Regular blood level monitoring is essential because lithium has a narrow therapeutic index — the target serum level is typically 0.6–0.8 mmol/L for maintenance therapy.
- Lithium is the only mood stabilizer proven to reduce suicide risk in patients with bipolar disorder and major depressive disorder.
- Common side effects include increased thirst, frequent urination, tremor, weight gain and thyroid changes, most of which can be managed with dose adjustments and monitoring.
- Many common medications including NSAIDs, ACE inhibitors and diuretics can dangerously increase lithium levels, so always inform your doctor about all medicines you take.
What Is Lithium and What Is It Used For?
Lithium has been used in psychiatry since the late 1940s and remains one of the most extensively studied medications in mental health. It was first approved for the treatment of mania in 1970 by the United States Food and Drug Administration (FDA) and has since been endorsed by every major international guideline for bipolar disorder, including the National Institute for Health and Care Excellence (NICE), the British Association for Psychopharmacology (BAP), and the Canadian Network for Mood and Anxiety Treatments (CANMAT).
The mechanism of action of lithium is complex and not fully understood. Research suggests it works by modulating several intracellular signaling pathways, including inhibition of glycogen synthase kinase-3 (GSK-3) and inositol monophosphatase, which are involved in neuronal cell survival, neuroplasticity and neurotransmitter regulation. These actions help stabilize neuronal membrane excitability, which is believed to be dysregulated in bipolar disorder.
Lithium is included on the World Health Organization (WHO) Model List of Essential Medicines, recognizing its fundamental importance in global mental healthcare. It is particularly notable for being the only psychiatric medication that has consistently demonstrated a reduction in suicide risk across multiple large-scale studies and meta-analyses.
Approved Indications
Lithium is approved for the following conditions in adults aged 18 years and older:
- Bipolar disorder — maintenance therapy: Prevention of manic and depressive episodes in patients with established bipolar disorder. This is the primary indication and where lithium has the strongest evidence base.
- Acute mania: Treatment of manic episodes characterized by elevated mood, reduced need for sleep, grandiosity, pressured speech and impulsive behavior.
- Treatment-resistant depression: Augmentation of antidepressant therapy in patients with major depressive disorder who have not responded adequately to antidepressants alone.
Lithium is not approved for use in children and adolescents under 18 years of age, as the safety and efficacy in this population have not been adequately established. Lithium carbonate, the active substance in commercially available formulations such as Carblit, may also be used for other conditions as determined by a physician, though such use would be considered off-label.
What Should You Know Before Taking Lithium?
Lithium therapy requires careful patient selection and thorough baseline investigations before treatment can begin. Because lithium has a narrow therapeutic index and is almost entirely eliminated by the kidneys, pre-treatment assessment focuses on renal, thyroid and cardiovascular function. Your doctor should perform blood tests including serum creatinine, estimated glomerular filtration rate (eGFR), thyroid function tests (TSH and free T4), serum calcium, and a full blood count before initiating treatment.
Contraindications
- You are allergic to lithium carbonate or any of the inactive ingredients
- You have a heart condition such as arrhythmia, Brugada syndrome or suspected Brugada syndrome
- You have a condition associated with low sodium levels (e.g. Addison's disease), other electrolyte disturbances, or are on a severely salt-restricted diet
- You have untreated hypothyroidism (underactive thyroid gland)
- You have severe kidney impairment
- You have Darier's disease (keratosis follicularis)
- You are breastfeeding
Warnings and Precautions
Inform your doctor before starting lithium if any of the following apply to you:
- You have or have had a blood clot in a vein (venous thrombosis)
- You have a family history of cardiac arrest or sudden death
- You are 40 years or older — an electrocardiogram (ECG) may be needed before starting treatment
- You have epilepsy or an increased risk of seizures
- You have any heart rhythm disorder
- You have low blood pressure
- You have significant muscle weakness (e.g. myasthenia gravis)
- You have psoriasis, as lithium may worsen this condition
- You are elderly, as dose adjustments and more frequent monitoring may be required
NMS is a rare but life-threatening reaction that can occur with the use of lithium, especially in combination with antipsychotic medications. Symptoms include high fever, muscle rigidity, excessive sweating and altered consciousness. NMS requires immediate emergency medical treatment. If you develop these symptoms, stop taking lithium and seek emergency care.
Long-term lithium use (over 10 years) may be associated with an increased risk of kidney tumors (microcysts, oncocytoma or renal tubular carcinoma), particularly in patients with significantly impaired kidney function. Regular ultrasound examinations of the kidneys may be recommended for long-term users. Your doctor should monitor kidney function with blood tests at least every 6–12 months throughout treatment.
Pregnancy and Breastfeeding
If you are pregnant, planning to become pregnant, or breastfeeding, discuss this with your doctor before taking lithium.
Pregnancy: Lithium crosses the placenta and can affect the developing fetus. While older studies suggested a high risk of cardiac malformations (particularly Ebstein's anomaly), more recent data indicate the absolute risk is relatively low, estimated at approximately 0.1–0.2% compared to 0.05% in the general population. However, this still represents a 2–4 fold increase in risk. The decision to continue or discontinue lithium during pregnancy must weigh the risks of fetal exposure against the potentially serious risks of untreated bipolar disorder during pregnancy. This decision should be made jointly with your psychiatrist and obstetrician.
Use of lithium near the time of delivery may cause neonatal toxicity including low Apgar scores, cyanosis (bluish discoloration due to low oxygen), reduced muscle tone, respiratory depression, lethargy, jaundice, and effects on heart and thyroid function. The newborn may require additional medical care after birth.
Breastfeeding: Lithium is excreted into breast milk at significant concentrations and breastfeeding is not recommended during lithium treatment, as it may cause adverse effects in the nursing infant.
Fertility: Lithium may affect fertility. If you are planning to start a family, discuss this with your doctor.
Driving and Operating Machinery
Lithium may have a mild to moderate effect on the ability to drive and operate machinery. Side effects such as drowsiness, tremor, dizziness and reduced concentration can impair your reaction time. Use particular caution at the start of treatment and after dose changes. Do not drive or operate heavy machinery until you know how lithium affects you.
How Does Lithium Interact with Other Drugs?
Drug interactions are among the most clinically significant safety concerns with lithium therapy. Because lithium is eliminated almost entirely through the kidneys and competes with sodium for renal reabsorption, any medication that affects kidney function, sodium balance, or fluid status can substantially alter lithium blood levels. Even modest changes in lithium levels can tip the balance between therapeutic efficacy and life-threatening toxicity.
Always inform your doctor, pharmacist or nurse about all medications you are taking, have recently taken, or plan to take, including over-the-counter medicines and herbal supplements.
Drugs That Increase Lithium Levels (Risk of Toxicity)
| Drug Class | Examples | Mechanism | Clinical Significance |
|---|---|---|---|
| ACE Inhibitors | Enalapril, lisinopril, ramipril | Reduce renal sodium excretion, increasing lithium reabsorption | High — monitor lithium levels closely |
| ARBs | Losartan, irbesartan, valsartan | Similar mechanism to ACE inhibitors | High — monitor lithium levels closely |
| Thiazide Diuretics | Hydrochlorothiazide, metolazone | Increase sodium loss, causing compensatory lithium reabsorption | Very high — avoid if possible |
| Loop Diuretics | Furosemide, bumetanide | Sodium and water depletion | High — frequent monitoring required |
| NSAIDs | Ibuprofen, naproxen, diclofenac | Reduce renal blood flow and glomerular filtration | High — use paracetamol instead |
| COX-2 Inhibitors | Celecoxib | Same as NSAIDs | High — monitor if unavoidable |
| Antibiotics | Metronidazole, trimethoprim, tetracyclines | May reduce renal lithium clearance | Moderate — monitor during course |
| Anticonvulsants | Phenytoin, carbamazepine | May increase lithium neurotoxicity | Moderate — watch for neurological symptoms |
Drugs That Decrease Lithium Levels
| Drug / Substance | Mechanism | Clinical Note |
|---|---|---|
| Sodium bicarbonate (antacids) | Increases renal lithium excretion through alkalinization | May reduce lithium effectiveness |
| Theophylline | Increases renal lithium clearance | May need higher lithium dose |
| Acetazolamide | Increases renal lithium excretion | Monitor lithium levels |
| Caffeine | Mild diuretic effect increasing lithium excretion | Keep caffeine intake consistent |
Drugs That May Cause Additive Side Effects
When combined with lithium, the following medications may increase the risk of adverse effects without necessarily changing lithium blood levels:
- Antipsychotics (haloperidol, olanzapine, clozapine) — increased risk of neurotoxicity, extrapyramidal symptoms and NMS
- Antidepressants (SSRIs such as citalopram, SNRIs such as venlafaxin, tricyclics such as amitriptyline) — increased risk of serotonin syndrome
- Opioids (buprenorphine) — enhanced CNS depression
- Iodine-containing medications — additive thyroid-suppressive effects
- Neuromuscular blocking agents — lithium may prolong their action during anesthesia
Take lithium at the same times each day, before or after meals, as prescribed by your doctor. This is necessary to maintain stable lithium levels in the blood. Do not significantly alter your dietary salt intake, fluid intake, or caffeine consumption without consulting your doctor, as these changes can affect lithium levels. If you experience stomach upset, taking lithium with food may help.
What Is the Correct Dosage of Lithium?
Always take lithium exactly as prescribed by your doctor. Dosing is individualized and your starting dose may differ from what is outlined below. Your doctor will consider your age, body weight, kidney function and the reason for treatment when determining the appropriate dose. The score line on the tablet is to facilitate easier swallowing and is not intended for dividing into equal doses.
Your doctor will take blood tests before, during and after initiating lithium treatment to check your serum lithium level. Blood samples for lithium monitoring should be taken 12 hours after the last dose (trough level).
Adults
Bipolar Disorder — Maintenance Therapy
Starting dose: 300 mg (1 tablet) once daily
Monitoring: Blood test after the first week to determine dose adjustment
Maintenance dose: Typically 600–1200 mg daily (2–4 tablets), adjusted based on serum levels
Target serum level: 0.6–0.8 mmol/L
Ongoing monitoring: Every 2–6 months once stable
Acute Mania
Starting dose: 1200–1500 mg daily (4–5 tablets), divided into 4 doses
Monitoring: Blood test every 2 days during dose titration
Target serum level: 0.8–1.0 mmol/L
Note: Higher initial doses are used to achieve rapid symptom control; dose will be reduced once the acute episode resolves
Augmentation for Treatment-Resistant Depression
Starting dose: 300 mg (1 tablet) twice daily
Monitoring: Blood test every 5 days until maintenance dose is reached
Maintenance dose: 600–900 mg daily (2–3 tablets), in 1–2 divided doses
Target serum level: 0.4–0.8 mmol/L
Elderly (Over 65 Years)
Elderly patients are more sensitive to lithium and require lower doses. The starting dose is typically lower and dose increases are more gradual. Target serum lithium levels are generally 0.4–0.6 mmol/L. More frequent monitoring of kidney function, thyroid function and lithium levels is required. Your doctor will adjust the dose and schedule regular check-ups accordingly.
Children and Adolescents (Under 18 Years)
Lithium is not recommended for use in children and adolescents under 18 years of age because the safety and efficacy in this population have not been established.
Patients with Kidney Impairment
Your doctor will check your kidney function before starting lithium. Patients with mild to moderate kidney impairment may require reduced doses and more frequent blood monitoring. Lithium is contraindicated in patients with severe kidney impairment. If your kidney function deteriorates during treatment, your doctor may need to reduce your dose or consider alternative medications.
Missed Dose
If you forget to take a dose, take it as soon as you remember — unless it is almost time for your next scheduled dose. In that case, skip the missed dose and continue with your regular schedule. Never take a double dose to make up for a missed one.
Overdose
If you have taken too much lithium, or if a child has accidentally ingested lithium, contact your local poison control center or emergency services immediately.
Signs of mild to moderate toxicity: Tremor, lethargy, fatigue, confusion, agitation, rapid pulse, slurred speech, muscle twitching, muscle rigidity, nausea, vomiting and diarrhea.
Signs of severe toxicity: Reduced consciousness, coma, seizures, very high body temperature, low blood pressure, slow or irregular heartbeat, and kidney failure. Severe lithium toxicity can be life-threatening.
Stopping Treatment
Do not stop taking lithium without first consulting your doctor. It is important to continue taking lithium even if you feel well. If treatment is stopped suddenly, there is a significant risk that symptoms of your condition will return, often more severely than before. Your doctor will advise you on how to taper the dose gradually if discontinuation is necessary.
What Are the Side Effects of Lithium?
Not all patients experience side effects from lithium, and many side effects are dose-related, meaning they can often be managed by adjusting the dose or timing of administration. Some side effects are more common during the initial weeks of treatment and may diminish over time. However, certain side effects require immediate medical attention.
- High fever, muscle rigidity, excessive sweating, altered consciousness (possible NMS — life-threatening)
- Very slow heart rate, fainting (possible AV block)
- Sudden shortness of breath, chest pain radiating to arms or neck, severe abdominal pain, paralysis, numbness, speech difficulties, painful swollen limbs (possible blood clots)
- General lethargy, recurrent infections, especially sore throat and fever (possible low white blood cell count)
Very Common
Affects more than 1 in 10 people
- Hypothyroidism (underactive thyroid) — fatigue, feeling cold, dry skin, hair loss, slow heart rate, constipation, hoarseness
- Goiter (enlarged thyroid gland — swelling in the neck)
- Weight gain
- Nephrogenic diabetes insipidus (increased urination and thirst)
Common
Affects 1 in 10 to 1 in 100 people
- Hyperparathyroidism (increased calcium levels — depression, thirst, muscle weakness)
- Increased thirst
- Confusion, drowsiness
- Tremor (fine hand tremor), reduced concentration and reaction time
- Diarrhea, nausea, abdominal pain (especially during early weeks)
- Acne
- Increased urine volume (polyuria)
- Edema (swelling due to fluid retention)
Uncommon
Affects 1 in 100 to 1 in 1,000 people
- Parkinsonian symptoms (slow involuntary movements, hand/head tremor, rigid movements, mask-like face) — reversible
- Headache, dizziness
- Sick sinus syndrome (slow or irregular heartbeat, confusion, dizziness, fainting, fatigue, breathlessness)
- Cardiac arrhythmia — may be or become serious, tell your doctor
- AV block (very slow heart rate, tendency to faint)
- Psoriasis or worsening of existing psoriasis, hair loss
- Muscle weakness
Rare
Affects fewer than 1 in 1,000 people
- Neuroleptic malignant syndrome (NMS) — high fever, muscle rigidity, excessive sweating, reduced consciousness (life-threatening)
Frequency Not Known
Reported but frequency cannot be estimated from available data
- Mild agranulocytosis (low white blood cell count — lethargy, recurrent infections, sore throat, fever)
- Blood clots (venous thrombosis, pulmonary embolism)
- Reversible leukocytosis (increased white blood cells — fever, fatigue, night sweats, weight loss)
- Thyrotoxicosis or hyperthyroidism (weight loss, rapid heartbeat, nervousness, heat sensitivity)
- Lichenoid drug reaction (skin or mucous membrane rash)
- Benign or malignant renal tumors (with long-term treatment)
- Renal impairment (nausea, reduced or absent urine output — with long-term treatment)
- Sexual dysfunction
- Visual disturbances
Lithium may also cause changes in certain laboratory tests that are not usually noticeable. These typically return to normal after treatment is discontinued. Your doctor will monitor relevant blood parameters throughout your treatment.
If you experience any side effects, including those not listed here, tell your doctor or pharmacist. You can also report side effects to your national medicines regulatory authority. Reporting helps to ensure the ongoing monitoring of the benefit-risk balance of medicines.
How Should You Store Lithium?
Lithium tablets do not require any special storage conditions. Store them at room temperature in the original container. The tablets typically come in an amber glass bottle with a plastic cap containing a silica gel desiccant to protect against moisture.
- Keep out of sight and reach of children — lithium toxicity can be extremely dangerous in children
- Check the expiry date — do not use lithium after the expiry date stated on the carton and bottle (marked "EXP"). The expiry date refers to the last day of that month
- Disposal — do not throw unused medicines into household waste or down the drain. Return unused medication to your pharmacist for safe disposal to help protect the environment
What Does Lithium Contain?
The active substance in lithium tablets is lithium carbonate. Each tablet contains 300 mg of lithium carbonate, which is equivalent to 56 mg of Li+ (lithium ions), corresponding to 8.1 mmol. Understanding the lithium ion content is important because serum lithium levels are measured in mmol/L.
Inactive Ingredients (Excipients)
- Colloidal anhydrous silicon dioxide
- Magnesium stearate
- Talc (E553b)
- Sodium starch glycolate (type A)
- Povidone
- Lactose monohydrate
- Maize starch
Lithium tablets contain lactose. If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine. The tablets contain less than 1 mmol sodium (23 mg) per tablet and are essentially sodium-free.
Appearance and Packaging
Lithium tablets are white, round, smooth tablets with beveled edges (size: 10 × 4 mm) and a score line on one side. They are supplied in a translucent, amber-colored glass bottle with a plastic cap containing silica gel desiccant to protect the tablets from moisture. Pack size: 100 tablets.
Frequently Asked Questions About Lithium
Lithium is primarily used to treat and prevent episodes of bipolar disorder (manic-depressive illness), including acute mania and bipolar depression. It is the gold standard mood stabilizer with over 60 years of clinical evidence. Lithium is also used as an augmentation therapy for treatment-resistant major depressive disorder when antidepressants alone have not been effective. It is the only mood stabilizer proven to reduce suicide risk in patients with mood disorders.
Blood monitoring frequency depends on your treatment phase. During dose initiation, blood lithium levels are checked every 2–5 days until stable. Once stabilized on a maintenance dose, lithium levels are typically checked every 2–6 months. Thyroid function tests (TSH) and kidney function tests (creatinine, eGFR) are performed at baseline and then at least every 6–12 months. More frequent monitoring may be needed if your dose changes, you become unwell, or you start new medications that interact with lithium.
Signs of mild to moderate lithium toxicity include a coarse tremor (noticeably worse than your usual fine tremor), drowsiness, confusion, slurred speech, muscle twitching, nausea, vomiting, and diarrhea. Severe toxicity can cause seizures, loss of consciousness, coma, dangerously low blood pressure, slow or irregular heartbeat, kidney failure, and can be life-threatening. Common triggers for toxicity include dehydration (e.g. from vomiting, diarrhea, fever, or hot weather), starting interacting medications, and kidney function deterioration. If you suspect toxicity, stop taking lithium and seek emergency medical help immediately.
NSAIDs such as ibuprofen, naproxen, and diclofenac should be avoided or used only under careful medical supervision while taking lithium, as they can significantly increase lithium levels in the blood and increase the risk of toxicity. Paracetamol (acetaminophen) is generally considered a safer alternative for pain relief. If an NSAID is essential, your doctor should check your lithium level more frequently during the course of treatment. Always consult your doctor or pharmacist before taking any new medication, including over-the-counter pain relievers.
Yes, weight gain is a very common side effect of lithium therapy, affecting more than 1 in 10 people. Studies report an average weight gain of 4–6 kg during treatment. Several factors contribute, including increased thirst (which may lead to consumption of sugary drinks), effects on thyroid function (hypothyroidism causes metabolic slowing), and possible direct metabolic effects. Maintaining a healthy diet, regular physical activity, drinking water rather than sugary beverages, and monitoring thyroid function can help manage weight. If significant weight gain occurs, discuss options with your doctor.
Lithium crosses the placenta and has been associated with a small increased risk of cardiac malformations in the fetus, particularly Ebstein's anomaly (a rare heart valve defect). However, more recent studies suggest the absolute risk is relatively low (approximately 0.1–0.2%, compared to 0.05% in the general population). The decision to continue or stop lithium during pregnancy is complex and must balance the risk to the baby against the substantial risk of untreated bipolar disorder to both the mother and the pregnancy. This decision should always be made together with your psychiatrist and obstetrician. Lithium is not recommended during breastfeeding as it passes into breast milk at significant levels.
References
This article is based on the following peer-reviewed sources, international guidelines and regulatory documents:
- National Institute for Health and Care Excellence (NICE). Bipolar disorder: assessment and management. Clinical guideline [CG185]. Updated 2023. Available at: nice.org.uk/guidance/cg185
- Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. doi:10.1111/bdi.12609
- Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30(6):495-553. doi:10.1177/0269881116636545
- Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013;346:f3646. doi:10.1136/bmj.f3646
- World Health Organization. WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- European Medicines Agency. Summary of Product Characteristics (SmPC) – Lithium Carbonate. EMA; 2024.
- McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721-728. doi:10.1016/S0140-6736(11)61516-X
- Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: Recommendations from clinical practice guidelines. J Affect Disord. 2017;217:266-280. doi:10.1016/j.jad.2017.03.052
- British National Formulary (BNF). Lithium carbonate. National Institute for Health and Care Excellence. Updated 2025.
- Tondo L, Alda M, Bauer M, et al. Clinical use of lithium salts: guide for users and prescribers. Int J Bipolar Disord. 2019;7(1):16. doi:10.1186/s40345-019-0151-2
Editorial Team
This article has been medically reviewed and approved by the iMedic Medical Editorial Team, consisting of board-certified specialists in psychiatry, clinical pharmacology and internal medicine.
All content undergoes a rigorous multi-step review: initial drafting by medical writers, clinical accuracy review by specialist physicians, evidence verification against current international guidelines (NICE, BAP, CANMAT, WHO), and final editorial approval.
This article adheres to Evidence Level 1A, the highest quality of evidence based on systematic reviews of randomized controlled trials and international clinical guidelines. We follow the GRADE evidence framework and declare no conflicts of interest or commercial funding.