Lithium is a foundational mood-stabilizing agent, primarily indicated for the management of bipolar disorder. Its efficacy is rooted in its ability to modulate key neurotransmitter systems and second messenger pathways within the central nervous system, leading to a significant reduction in the frequency and severity of manic episodes. Proper therapeutic use requires strict adherence to dosing protocols and consistent serum level monitoring to maximize benefits and minimize risks. This agent represents a cornerstone of long-term psychiatric pharmacotherapy for many patients.

Features

• Active pharmaceutical ingredient: Lithium carbonate or lithium citrate
• Available in standard-release tablets, capsules, and liquid oral solution formulations
• Mechanism of action: Modulates inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) pathways
• Exhibits complex effects on serotonin, dopamine, and glutamate neurotransmission
• Requires precise therapeutic drug monitoring (TDM) for safe and effective use
• Narrow therapeutic index necessitates careful dose titration

Benefits

• Provides effective prophylaxis against recurrent manic and depressive episodes in bipolar I disorder
• Demonstrates significant anti-suicidal properties, reducing associated morbidity and mortality
• Helps stabilize mood cycling, allowing for improved psychosocial functioning and quality of life
• Offers a well-established long-term treatment profile with decades of clinical evidence
• Can be used as an augmenting agent for treatment-resistant major depressive disorder

Common use

Lithium is predominantly prescribed for the treatment and maintenance therapy of bipolar I disorder, characterized by recurrent episodes of mania and depression. It is highly effective in controlling acute mania and preventing future mood episodes. It is also used off-label as an augmentation strategy for treatment-resistant unipolar depression and may sometimes be considered for certain cluster headache syndromes. Its use is almost always within the context of a comprehensive treatment plan that includes psychotherapy.

Dosage and direction

Dosage is highly individualized and titrated based on serum lithium levels, patient response, and tolerability. Treatment is typically initiated at a low dose (e.g., 300 mg twice daily for lithium carbonate) and gradually increased.

• Serum Monitoring: The therapeutic range for acute mania is typically 0.8-1.0 mmol/L. For maintenance therapy, levels are often maintained between 0.6-0.8 mmol/L.
• Administration: Oral formulations are taken with meals to minimize gastrointestinal upset. Consistent timing of doses is critical.
• Frequency: Usually administered two or three times daily, though extended-release formulations may allow for once-daily dosing.
• Titration: Dose adjustments should only be made under direct physician supervision, with serum levels checked 5-7 days after each change.
• Monitoring Schedule: Serum levels are checked regularly (e.g., every 3-6 months during stable maintenance) and more frequently during illness, dosage changes, or if toxicity is suspected.

Precautions

Vigilant monitoring and patient education are paramount due to lithium’s narrow therapeutic index.

• Renal Function: Lithium is excreted renally. Baseline assessment of renal function (e.g., serum creatinine, eGFR) is required before initiation, with regular monitoring thereafter.
• Thyroid Function: Lithium can cause hypothyroidism and goiter. Baseline and periodic TSH levels are mandatory.
• Cardiac Function: Use with caution in patients with cardiovascular disease, as lithium can cause ECG changes (e.g., T-wave flattening or inversion).
• Fluid and Electrolyte Balance: Maintain normal fluid and sodium intake. Dehydration, diarrhea, vomiting, or use of diuretics can precipitously increase serum lithium levels, leading to toxicity.
• Pregnancy and Lactation: Use during pregnancy requires a meticulous risk-benefit analysis (Pregnancy Category D). Lithium is excreted in breast milk.
• Cognitive and Neuromuscular Effects: Can cause mild cognitive impairment, fine tremor, and lethargy, which may affect tasks requiring mental alertness or motor coordination.

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 history of Brugada syndrome
• Known hypersensitivity to lithium or any component of the formulation

Possible side effect

Side effects are often dose-dependent and may be related to peak serum levels.

• Common: Fine hand tremor, polyuria, polydipsia, mild nausea, loose stools, weight gain, fatigue.
• Less Common: Cognitive dulling, memory problems, acneiform eruptions, psoriasis exacerbation, hypothyroidism, leukocytosis.
• Serious (Require Medical Attention): Coarse tremor, persistent nausea/vomiting/diarrhea, ataxia, slurred speech, blurred vision, dizziness, muscle twitching, arrhythmias, edema. These are often signs of emerging toxicity.

Drug interaction

Lithium interacts with numerous medications, primarily those affecting its excretion or toxicity profile.

• Diuretics (especially thiazides): Increase lithium reabsorption, markedly elevating serum levels and risk of toxicity.
• NSAIDs (e.g., ibuprofen, naproxen): Can decrease renal clearance of lithium, increasing levels.
• ACE Inhibitors & ARBs: May increase lithium levels.
• Metronidazole: Case reports suggest increased lithium levels.
• 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 it is remembered on the same day. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Patients should never double the next dose to make up for a missed one, as this can acutely raise serum levels and precipitate toxicity. Consistency in dosing is critical for maintaining stable serum levels.

Overdose

Lithium overdose is a medical emergency, with toxicity occurring 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, blurred vision) and can lead to seizures, coma, permanent neurological damage, and death. Treatment involves immediate discontinuation of lithium, aggressive hydration with saline IV fluids to enhance excretion, and in severe cases, hemodialysis to rapidly remove lithium from the bloodstream. Management must occur in a hospital setting.

Storage

Store at room temperature (20-25°C or 68-77°F) in a tightly closed container, away from light, moisture, and heat. Keep all medications out of reach of children and pets. Do not store in bathrooms or other damp places. Do not use after the expiration date on the label. Liquid formulations should not be frozen.

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 physician or other qualified health provider with any questions you may have regarding a medical condition or before starting or altering any treatment regimen. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content provided has been compiled from various sources and may not be entirely accurate or comprehensive for every individual.

Reviews

“Lithium has been the bedrock of my stability for over a decade. While the initial side effects like tremor were challenging and the required blood tests are a commitment, the payoff is a life not ruled by the extreme cycles of my bipolar disorder. It gave me my life back.” – M.C., long-term patient.

“From a clinical perspective, lithium remains the gold standard mood stabilizer for bipolar I disorder. Its anti-suicidal efficacy is unmatched by other agents. Managing it requires a diligent partnership with the patient for monitoring, but the long-term outcomes in compliant patients are often exceptional.” – Dr. A. Sharma, Psychiatrist.

“The necessity of constant hydration and blood work can be burdensome, and the weight gain was significant for me. However, after trying several other medications that were ineffective, lithium was the only one that truly controlled my manic episodes. The trade-offs are worth it for the stability.” – J.L., patient.