Lithium is a foundational mood-stabilizing agent with a well-established efficacy profile in the long-term management of bipolar disorder. Its primary therapeutic action is believed to stem from complex interactions with neuronal signaling pathways, particularly those involving inositol metabolism and glycogen synthase kinase-3 (GSK-3) inhibition, leading to a reduction in the frequency and severity of manic episodes and a prophylactic effect against recurrent depression. Clinical use requires meticulous serum level monitoring to maintain a narrow therapeutic index, balancing maximal efficacy with minimal adverse effects. This agent represents a cornerstone of psychiatric pharmacotherapy for a specific patient population.

Features

• Active pharmaceutical ingredient: Lithium carbonate or lithium citrate
• Standard available dosages: 150 mg, 300 mg, 450 mg, 600 mg extended-release tablets; 8 mEq/5 mL liquid solution
• Mechanism of Action: Multimodal; includes inhibition of inositol monophosphatase, modulation of second messenger systems, and effects on gene expression regulation
• Administration: Oral
• Bioavailability: Nearly complete and rapid for immediate-release formulations
• Protein Binding: None
• Metabolism: Not metabolized; eliminated unchanged by the kidneys
• Half-life: Approximately 24 hours (varies with age and renal function)
• Therapeutic Serum Range: 0.6–1.2 mmol/L for acute mania; 0.8–1.0 mmol/L for maintenance therapy (specific targets are patient- and context-dependent)

Benefits

• Provides effective prophylaxis against recurrent manic and depressive episodes in bipolar I disorder.
• Demonstrates significant anti-suicidal properties, reducing the risk of suicide and suicide attempts in the affected population.
• Offers a stabilizing effect on mood, reducing the amplitude of cyclical mood swings.
• Can be used as an augmenting agent in treatment-resistant major depressive disorder.
• Has a long history of clinical use, resulting in a deep and well-understood safety and efficacy profile.

Common use

Lithium is primarily indicated for the treatment of bipolar I disorder for the acute management of manic episodes and for maintenance therapy to prevent or diminish the intensity of subsequent episodes. It is also used as an augmentation strategy in cases of treatment-resistant unipolar depression. Its use is almost exclusively within the psychiatric domain and is always initiated and managed by a specialist physician due to the requisite monitoring and narrow therapeutic window.

Dosage and direction

Dosage is highly individualized based on patient response, tolerability, and serum lithium concentrations. Treatment must be initiated at a low dose with gradual upward titration.

• Adults (Bipolar Mania): The typical initial dosage is 600–900 mg per day of lithium carbonate (or equivalent), administered in two or three divided doses, or once daily for extended-release formulations. Dosage is adjusted every 3–7 days based on serum levels and clinical response to achieve a target serum lithium concentration.
• Adults (Maintenance Therapy): The dosage is adjusted to maintain a serum lithium level typically between 0.6 and 1.0 mmol/L. The total daily dose often ranges from 900 mg to 1200 mg but can vary significantly.
• Geriatric or Debilitated Patients: Initiate at significantly lower doses (e.g., 300 mg once or twice daily) due to reduced renal clearance and increased susceptibility to adverse effects.
• Administration: Tablets should be swallowed whole with a full glass of water. The liquid solution should be measured carefully with the provided dosing syringe or cup. Consistent administration with or without food is recommended to minimize gastrointestinal upset and maintain steady absorption. Maintaining adequate and consistent fluid intake is crucial.

Precautions

• Renal Function Monitoring: Baseline assessment of renal function (e.g., serum creatinine, estimated GFR) is mandatory before initiation. Renal function must be monitored regularly (e.g., every 3-6 months initially, then annually if stable) during treatment, as long-term use can cause nephrogenic diabetes insipidus or chronic interstitial nephropathy.
• Thyroid Function Monitoring: Lithium can cause hypothyroidism and/or goiter. Baseline thyroid function tests (TSH, T4) are required, with monitoring every 6-12 months during therapy.
• Serum Level Monitoring: Serum lithium levels must be checked regularly (e.g., 5-7 days after initiation or dose change, then every 3-6 months during maintenance). Levels should be drawn 12 hours post-dose (trough level).
• Fluid and Electrolyte Balance: Patients must maintain a normal diet with consistent salt and fluid intake. Dehydration, febrile illness, diarrhea, vomiting, or use of diuretics can precipitously increase serum lithium levels and risk of toxicity. Patients should be educated to ensure adequate hydration, especially during exercise or hot weather.
• Pregnancy and Lactation: Lithium use in pregnancy is associated with a known risk of cardiac malformations (e.g., Ebstein’s anomaly), especially during the first trimester. Use during pregnancy requires a meticulous risk-benefit analysis and specialist consultation. Lithium is excreted in breast milk and is not generally recommended during breastfeeding.

Contraindications

• Significant renal impairment or severe renal disease.
• Cardiovascular disease with significant sodium depletion.
• Severe debilitation, dehydration, or sodium depletion.
• Known hypersensitivity to lithium or any component of the formulation.
• In patients where consistent serum level monitoring is not feasible.

Possible side effect

Side effects are often dose-dependent and/or related to serum concentration.

• Common: Fine hand tremor, polyuria (increased urination), polydipsia (increased thirst), mild nausea, general discomfort, weight gain.
• Less Common: Diarrhea, vomiting, drowsiness, muscle weakness, dermatological conditions (e.g., acne, psoriasis exacerbation).
• Serious (require medical attention): Coarse tremor, persistent nausea/vomiting/diarrhea, ataxia (loss of coordination), slurred speech, blurred vision, tinnitus, confusion, seizures, excessive polyuria/polydipsia (signs of nephrogenic diabetes insipidus). These are often signs of emerging toxicity.

Drug interaction

Lithium has a high potential for significant pharmacokinetic and pharmacodynamic interactions.

• Diuretics (especially Thiazides): Markedly increase lithium reabsorption and can cause rapid onset of toxicity. Loop diuretics pose a lower risk. Concomitant use requires extreme caution and more frequent monitoring.
• NSAIDs (e.g., Ibuprofen, Naproxen): Can decrease renal clearance of lithium, elevating serum levels. Avoid or use with great caution and increased monitoring.
• ACE Inhibitors & ARBs: Can increase serum lithium concentrations.
• Serotonergic Drugs (e.g., SSRIs, SNRIs): May increase the risk of serotonin syndrome.
• Antipsychotics: May increase the risk of extrapyramidal symptoms (EPS) or neuroleptic malignant syndrome (NMS).

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If it is almost time for the next scheduled dose, the missed dose should be skipped. The regular dosing schedule should be resumed. A double dose should never be taken to make up for a missed one, as this could precipitously raise serum levels and cause toxicity.

Overdose

Lithium overdose is a medical emergency. Toxicity can occur at levels only slightly above the therapeutic range. Symptoms progress from gastrointestinal (nausea, vomiting, diarrhea) to neurological (drowsiness, slurred speech, coarse tremor, muscle twitching, ataxia, confusion). Severe toxicity can lead to coma, irreversible neurological damage, and death. Treatment involves immediate discontinuation of lithium, aggressive hydration with intravenous saline to enhance excretion, and in severe cases, hemodialysis to rapidly remove lithium from the bloodstream. Serum lithium levels and electrolyte status must be monitored in a hospital setting.

Storage

• Store at controlled room temperature (20°C to 25°C or 68°F to 77°F).
• Protect from light and moisture.
• Keep the container tightly closed.
• Keep all medications out of the reach of children and pets.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your qualified healthcare provider with any questions you may have regarding a medical condition or before starting, stopping, or changing any prescribed part of your care plan. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

“After a decade of cycling through various states of mania and depression, lithium provided the stability I desperately needed. The required blood tests are a small price to pay for a functional life.” – J.D., patient for 8 years.

“Managing lithium therapy requires a disciplined partnership between the clinician and patient. Its efficacy in preventing relapse in bipolar I is unparalleled, but it demands respect for its narrow therapeutic index and potential organ toxicities. Consistent monitoring is non-negotiable.” – Dr. A. Rivera, Board-Certified Psychiatrist.

“The initial side effects, particularly the tremor and thirst, were challenging to adjust to. However, with careful dose adjustment by my doctor, they have become much more manageable. The trade-off for mood stability has been unequivocally worth it.” – M.K., patient for 3 years.