Lithium is a foundational mood-stabilizing agent, primarily indicated for the management of bipolar disorder. Its efficacy is attributed to its unique neurochemical properties that modulate key neurotransmitter systems and intracellular signaling pathways, leading to a significant reduction in the frequency and severity of manic episodes and a prophylactic effect against recurrent depression. Treatment requires meticulous medical supervision due to its narrow therapeutic index, necessitating regular serum level monitoring to ensure both efficacy and patient safety. This agent represents a cornerstone of long-term psychiatric pharmacotherapy for appropriate patient populations.

Features

• Active pharmaceutical ingredient: Lithium carbonate or lithium citrate.
• Mechanism of action: Modulates inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) signaling pathways; influences second messenger systems and neurotransmitter release.
• Standard formulations include immediate-release and controlled-release tablets, capsules, and liquid solutions.
• Characterized by a well-established pharmacokinetic profile with nearly complete bioavailability.
• Requires therapeutic drug monitoring (TDM) to maintain serum levels within the narrow therapeutic window of 0.6–1.2 mmol/L for acute mania and 0.6–0.8 mmol/L for maintenance.
• Elimination is primarily renal, unchanged by metabolism.

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 treated populations.
• Offers long-term mood stabilization, enabling improved social and occupational functioning.
• Possesses a well-understood safety profile when managed correctly with appropriate monitoring protocols.
• Serves as a first-line treatment option for acute mania and maintenance therapy per major clinical guidelines.

Common use

Lithium is predominantly prescribed for the treatment and prophylaxis of bipolar I disorder, specifically for managing acute manic episodes and preventing future episodes of mania and depression. It is also used as an augmenting agent in treatment-resistant major depressive disorder. Its use is strictly contingent upon a confirmed diagnosis by a qualified psychiatrist and is not indicated for other forms of mood dysregulation or as a first-line treatment for other conditions without specialist consultation.

Dosage and direction

Dosage is highly individualized and must be titrated based on serum lithium concentrations, patient response, and tolerability. Treatment is always initiated at a low dose.

• Initial dosing: For adults, typically 300–600 mg daily (of lithium carbonate), administered in two or three divided doses or as a single daily dose for extended-release formulations.
• Titration: The dose is gradually increased every 3–5 days based on serum levels drawn 12 hours post-dose.
• Target serum levels:
  • Acute mania: 0.8–1.2 mmol/L
  • Maintenance therapy: 0.6–0.8 mmol/L
• Administration: Should be taken with food or milk to minimize gastrointestinal upset. Consistent hydration is crucial. Patients must adhere strictly to the prescribed regimen and timing of blood tests.

Precautions

Vigilant monitoring is required throughout treatment due to lithium’s narrow therapeutic index.

• Renal function: Baseline assessment of serum creatinine and estimated glomerular filtration rate (eGFR) is mandatory. Renal function must be monitored regularly (e.g., every 3–6 months initially, then annually if stable) due to the risk of nephrogenic diabetes insipidus and chronic kidney disease.
• Thyroid function: Lithium can induce hypothyroidism and goiter. Baseline TSH is required, with monitoring every 6-12 months.
• Cardiac function: ECG is recommended at baseline in patients with pre-existing cardiac disease or risk factors.
• Electrolytes: Sodium levels must be maintained; dehydration or hyponatremia can precipitously increase serum lithium levels, leading to toxicity.
• Pregnancy and Lactation: Lithium is associated with cardiac teratogenicity (Ebstein’s anomaly) and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is excreted in breast milk; a risk-benefit analysis is required for nursing mothers.

Contraindications

Lithium is contraindicated in patients with:

• Significant renal impairment or severe renal disease.
• Cardiovascular disease with severe sodium depletion.
• Addison’s disease or other untreated adrenal insufficiency.
• Brugada syndrome or known susceptibility to it.
• Known hypersensitivity to lithium or any component of the formulation.

Possible side effect

Side effects are often dose-dependent and may include:

• Common: Fine hand tremor, polyuria, polydipsia, mild nausea, diarrhea, weight gain.
• Neurological: Fatigue, lethargy, memory/concentration difficulties.
• Dermatological: Acneiform eruptions, psoriasis exacerbation.
• Endocrine: Hypothyroidism, goiter, hyperparathyroidism.
• Renal: Nephrogenic diabetes insipidus (manifesting as polyuria and polydipsia), chronic interstitial nephritis with long-term use.
• Cardiac: Benign, reversible T-wave flattening or inversion on ECG.

Drug interaction

Lithium has numerous clinically significant drug interactions that can alter its serum concentration.

• Drugs that increase lithium levels: NSAIDs (e.g., ibuprofen, naproxen), ACE inhibitors, ARBs, diuretics (especially thiazides), metronidazole.
• Drugs that decrease lithium levels: Theophylline, sodium bicarbonate, acetazolamide.
• Pharmacodynamic interactions: Concomitant use with antipsychotics may increase the risk of extrapyramidal symptoms (EPS) or neuroleptic malignant syndrome (NMS). Concomitant use with SSRIs, SNRIs, or tramadol may increase serotonin syndrome risk. Concomitant use with drugs that prolong the QT interval may have additive effects.

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 dose, the missed dose should be skipped. The regular dosing schedule should be resumed. The patient should never take a double dose to make up for a missed one. Consistent daily intake is critical for maintaining stable serum levels.

Overdose

Lithium overdose is a medical emergency. Toxicity can occur intentionally or accidentally, even at doses close to therapeutic levels in susceptible individuals (e.g., those who are dehydrated).

• Early signs: Severe nausea, vomiting, diarrhea, drowsiness, muscle weakness, coarse tremor.
• Advanced signs: Ataxia, giddiness, tinnitus, blurred vision, clonic movements, hyperreflexia, seizures, coma, cardiovascular collapse.
• Treatment: Requires immediate hospitalization. Gastric lavage may be considered if presentation is early. The cornerstone of management is aggressive hydration with intravenous saline to enhance renal excretion. In severe cases, hemodialysis is the definitive treatment to rapidly remove lithium from the bloodstream.

Storage

• Store at controlled room temperature (20°–25°C or 68°–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 psychiatrist or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The use of lithium must be managed by a healthcare professional familiar with its pharmacology and monitoring requirements.

Reviews

• “As a treating psychiatrist for over 20 years, lithium remains my gold standard for bipolar prophylaxis. Its anti-suicidal efficacy is unparalleled. The necessity for monitoring is a small price to pay for the profound stability it offers appropriate patients.” – Dr. E. Vance, MD.
• “After a decade of cycling through episodes that disrupted my life, lithium therapy provided the consistent stability I needed to rebuild. The regular blood tests are a part of my routine that I gladly accept for the wellness it affords me.” – Patient M., 6 years on therapy.
• “From a clinical pharmacology standpoint, lithium is a fascinating drug. Its narrow therapeutic index demands respect and precision in management, but its mechanism and effectiveness solidify its irreplaceable role in neuropsychiatry.” – Clinical Pharmacist Specialist.