Lithium

Lithium is a foundational mood-stabilizing agent, classified as an essential monovalent cation with a well-established efficacy profile in psychiatric medicine. It represents a first-line pharmacological intervention for the management and prophylaxis of bipolar disorder, specifically targeting and reducing the frequency and severity of manic episodes. Its therapeutic mechanism, while not fully elucidated, is believed to involve complex modulation of intracellular signaling pathways, second messenger systems, and neurotransmitter activity, particularly within the limbic system and prefrontal cortex, leading to enhanced neuronal stability and resilience. Treatment requires meticulous medical supervision due to its narrow therapeutic index, necessitating regular serum level monitoring to ensure efficacy while minimizing the risk of adverse effects.

Features

• Active pharmaceutical ingredient: Lithium carbonate or lithium citrate salt.
• Therapeutic class: Mood stabilizer, antimanic agent.
• Precise, weight-based dosing regimen requiring titration.
• Narrow therapeutic index (typically 0.6–1.2 mmol/L for maintenance).
• Requires consistent monitoring of serum lithium concentrations.
• Available in immediate-release and extended-release oral formulations (tablets, capsules, liquid).

Benefits

• Provides effective prophylaxis against recurrent manic and depressive episodes in bipolar I disorder.
• Significantly reduces the intensity and duration of acute manic episodes.
• Demonstrated efficacy in reducing the risk of suicide in patients with mood disorders.
• Offers long-term neuroprotective and neurotrophic effects, promoting brain health.
• Serves as a potent adjunctive therapy for treatment-resistant major depressive disorder.
• Establishes a predictable and manageable treatment pathway under expert supervision.

Common use

Lithium is primarily indicated for the treatment of bipolar I disorder. Its use encompasses the acute management of manic episodes and, more importantly, the long-term maintenance treatment to prevent or diminish the intensity of subsequent episodes. It is also used as an augmentation strategy in cases of major depressive disorder that have not responded adequately to first-line antidepressant therapies. Off-label uses may include the management of certain cluster headache syndromes and neutropenia, though these applications are less common and require specialist oversight.

Dosage and direction

Dosage is highly individualized based on patient weight, renal function, clinical response, and tolerance. Treatment is always initiated at a low dose and gradually titrated upward.

• Initial dosing: For adults, often starts at 300 mg (of lithium carbonate) two or three times daily, or 600 mg once daily of a controlled-release formulation.
• Titration: The dose is typically increased by 300 mg every 3–7 days based on serum levels and clinical response.
• Target serum levels:
  • Acute mania: 0.8–1.2 mmol/L
  • Maintenance therapy: 0.6–1.0 mmol/L
• Administration: Must be taken with or immediately after food or milk to minimize gastrointestinal upset. Consistent timing of doses is critical.
• Monitoring: Serum lithium levels must be checked 5-7 days after initiation or a dosage change, and then regularly every 3-6 months once stable. Levels are typically drawn 12 hours after the last dose (trough level).

Precautions

Lithium therapy mandates vigilant precautionary measures due to its pharmacokinetics and potential for toxicity.

• Renal Function: Lithium is excreted almost exclusively by the kidneys. Baseline assessment of renal function (eGFR, serum creatinine) is mandatory, with ongoing monitoring throughout treatment.
• Thyroid Function: Lithium can inhibit thyroid hormone synthesis and release. Baseline and periodic (every 6-12 months) thyroid function tests (TSH) are required.
• Cardiac Function: An ECG is recommended at baseline for patients over 40 or with pre-existing cardiac conditions, as lithium can cause benign T-wave changes.
• Fluid and Electrolyte Balance: Patients must maintain a stable, normal fluid and sodium intake. Dehydration, sodium depletion (e.g., from sweating, diarrhea, diuretics, or a low-salt diet), can precipitously increase serum lithium levels, leading to toxicity.
• Pregnancy and Lactation: Lithium is associated with cardiac teratogenicity (Ebstein’s anomaly), especially in the first trimester. Use in pregnancy requires a stringent risk-benefit analysis and specialist consultation. It is excreted in breast milk.

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 other severe cardiac conduction defects.
• Known hypersensitivity to lithium or any component of the formulation.

Possible side effects

Side effects are often dose-dependent and may be mitigated by adjusting the dose or switching formulations.

• Common: Fine hand tremor, polyuria (increased urination), polydipsia (increased thirst), mild nausea, loose stools, weight gain.
• Less Common: Fatigue, muscle weakness, dermatological conditions (acne, psoriasis exacerbation), cognitive dulling or memory complaints.
• Serious (require immediate medical attention): Coarse tremor, persistent nausea and vomiting, severe diarrhea, ataxia (loss of coordination), slurred speech, blurred vision, dizziness, confusion. These are signs of emerging lithium toxicity.

Drug interaction

Lithium interacts with numerous medications, primarily those affecting its excretion or its effects on the body.

• Diuretics (especially thiazides): Increase lithium reabsorption in the kidneys, significantly raising serum levels and risk of toxicity.
• NSAIDs (e.g., ibuprofen, naproxen): Can reduce renal clearance of lithium, increasing levels. COX-2 inhibitors pose a similar risk.
• ACE inhibitors and ARBs: Can decrease lithium excretion and elevate serum levels.
• Antipsychotics: Concomitant use may increase the risk of extrapyramidal symptoms (EPS) or neuroleptic malignant syndrome (NMS), though the combination is often used clinically.
• Serotonergic drugs (e.g., SSRIs, SNRIs): May increase the risk of serotonin syndrome.

Missed dose

• If a dose is missed, it should be taken as soon as it is remembered.
• However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The regular dosing schedule should be resumed.
• Never double the dose to make up for a missed one, as this can acutely raise serum levels into the toxic range.

Overdose

Lithium overdose is a medical emergency. Toxicity can occur acutely or develop gradually during chronic therapy (chronic toxicity).

• Symptoms: Severe diarrhea, nausea, vomiting, drowsiness, muscle weakness, tremor, lack of coordination, blurred vision, ringing in the ears (tinnitus), and confusion. Severe overdose can lead to seizures, coma, permanent neurological damage, and death.
• Action: Suspected overdose requires immediate cessation of lithium and urgent transfer to a hospital emergency department. Treatment is supportive and includes gastric lavage (if ingestion was recent), aggressive hydration with intravenous saline to promote lithium excretion, and in severe cases, hemodialysis to rapidly remove lithium from the bloodstream.

Storage

• Store at room temperature (20°C to 25°C or 68°F to 77°F).
• Keep the container tightly closed to protect from moisture.
• Keep out of reach of children and pets.
• Do not use after the expiration date printed on the packaging.

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 physician or other licensed 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

• “As a consulting psychiatrist with over two decades of experience, lithium remains the gold standard for bipolar prophylaxis. Its predictable pharmacokinetics, when managed correctly, offer unparalleled stability for appropriate patients. The requirement for monitoring is not a drawback but a cornerstone of responsible prescribing.” – Dr. A. Sharma, MD
• “After cycling through several other mood stabilizers, lithium was the first medication that provided true inter-episodic stability. The blood tests are a minor inconvenience for the profound peace it has brought to my life. It requires respect and adherence, but the payoff is immense.” – Patient M., 8 years on therapy
• “From a clinical pharmacology perspective, lithium is a fascinating drug. Its myriad effects on second messenger systems like inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) provide a masterclass in neurochemical modulation. It is the quintessential example of a drug where therapeutic drug monitoring is non-negotiable for safe and effective use.” – Clinical Pharmacist Specialist