Lithium is a foundational mood-stabilizing agent, primarily indicated for the management of bipolar disorder. Its efficacy is rooted in its unique ability to modulate key neurotransmitter systems and intracellular signaling pathways, reducing the frequency and severity of manic episodes and helping to prevent recurrent depressive phases. This monograph provides a comprehensive, evidence-based overview for healthcare professionals, detailing its pharmacological profile, clinical applications, and essential management protocols to ensure both therapeutic success and patient safety.

Features

• Active pharmaceutical ingredient: Lithium carbonate or lithium citrate
• Available in immediate-release and extended-release oral formulations (tablets, capsules, solution)
• Standard strengths: 150 mg, 300 mg, 450 mg lithium carbonate equivalents
• Precise serum level monitoring required (therapeutic range typically 0.6–1.2 mmol/L)
• Well-established pharmacokinetics with nearly complete gastrointestinal absorption
• Narrow therapeutic index necessitates careful dosing titration

Benefits

• Provides robust prophylaxis against manic and hypomanic episodes in bipolar I disorder
• Demonstrates significant anti-suicidal properties, reducing mortality risk
• Augments efficacy of antidepressants in treatment-resistant major depressive episodes
• Offers long-term neuroprotective potential, potentially slowing disease progression
• Stabilizes mood cycling, improving overall psychosocial functioning and quality of life
• Supported by decades of clinical evidence establishing its gold-standard status

Common use

Lithium is predominantly prescribed for the acute treatment and maintenance therapy of bipolar I disorder, characterized by recurrent episodes of mania and depression. It is recognized as a first-line agent for preventing relapse and managing acute mania. Off-label applications include its use as an augmenting agent in treatment-resistant unipolar depression, and it is sometimes utilized in specific cluster headache protocols. Its use requires confirmed diagnosis by a psychiatric specialist and initiation under careful clinical supervision.

Dosage and direction

Dosage is highly individualized and must be titrated based on serum lithium levels, renal function, age, and clinical response. For adults, initial dosing often begins at 300 mg two to three times daily for carbonate formulations, or equivalent dosing for citrate. Target serum levels for acute mania are generally 0.8–1.2 mmol/L, drawn 12 hours post-dose. For maintenance therapy, levels of 0.6–0.8 mmol/L are often sufficient. Dosage adjustments should be made no more frequently than every 5–7 days to allow for steady-state concentration. Extended-release formulations are typically administered twice daily. Patients must be instructed to take lithium with food or milk to minimize gastrointestinal upset and to maintain consistent hydration and sodium intake.

Precautions

Regular monitoring of serum lithium levels, renal function (serum creatinine and estimated GFR), thyroid function (TSH), and electrolytes is mandatory. Patients should be advised to maintain adequate and consistent fluid intake (2–3 L/day) and a stable dietary salt intake. Caution is required in conditions causing sodium depletion (e.g., prolonged sweating, diarrhea, diuretic use, low-salt diets), as this can precipitously increase lithium levels and risk of toxicity. Use with extreme caution in elderly patients and those with any degree of renal impairment. Electroconvulsive therapy (ECT) concurrent with lithium may increase the risk of neurotoxic effects and is generally not recommended.

Contraindications

Lithium is contraindicated in patients with severe renal impairment (e.g., CrCl <30 mL/min), significant cardiovascular disease, severe debilitation or dehydration, or untreated hypothyroidism. It is also contraindicated in pregnancy, especially during the first trimester, due to a well-established risk of cardiac malformations (Ebstein’s anomaly). Use during breastfeeding is not recommended due to secretion into breast milk. Known hypersensitivity to lithium or any component of the formulation is an absolute contraindication.

Possible side effect

• Common (>10%): Fine hand tremor, polyuria, polydipsia, mild nausea, weight gain.
• Less common (1-10%): Fatigue, muscle weakness, hypothyroidism, mild cognitive slowing (e.g., memory problems), diarrhea, acne, or psoriasis exacerbation.
• Rare (<1%): Nephrogenic diabetes insipidus, leukocytosis, ECG changes (e.g., T-wave flattening), hyperparathyroidism.
• Many side effects are dose-dependent and may be mitigated by adjusting the dose or switching to a slow-release formulation.

Drug interaction

• Diuretics (especially thiazides): Significantly increase lithium levels and risk of toxicity; avoid combination if possible.
• NSAIDs (e.g., ibuprofen, naproxen): Can decrease renal clearance of lithium, elevating serum levels.
• ACE inhibitors, ARBs: May increase lithium concentrations.
• Serotonergic drugs (e.g., SSRIs, SNRIs): May increase risk of serotonin syndrome.
• Antipsychotics: May increase risk of extrapyramidal symptoms or neurotoxicity.
• Methyldopa, phenytoin, carbamazepine: Potential for increased toxicity or reduced efficacy. A thorough medication review is essential before initiation and during therapy.

Missed dose

If a dose is missed, it should be taken as soon as possible on the same day. However, if it is close to the 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 elevate serum levels and precipitate toxicity. Consistency in dosing timing is critical for maintaining stable serum concentrations.

Overdose

Lithium overdose is a medical emergency, with toxicity possible even at levels only slightly above the therapeutic range. Symptoms progress from mild (coarse tremor, nausea, vomiting, diarrhea, drowsiness) to severe (gross tremor, confusion, nystagmus, seizures, coma, cardiovascular collapse). Chronic toxicity can occur with levels in the therapeutic range if renal function declines. Treatment involves immediate discontinuation of lithium, aggressive hydration with saline IV fluids to enhance excretion, and continuous monitoring of electrolytes and neurological status. In severe cases, hemodialysis is the definitive treatment to rapidly remove lithium from the bloodstream.

Storage

Store at room temperature (20–25°C or 68–77°F), in a tightly closed container, protected from light and moisture. Keep all medications out of the reach of children and pets. Do not use after the expiration date printed on the bottle. Do not store in bathrooms or damp areas.

Disclaimer

This information is intended for educational purposes and for use by qualified healthcare professionals only. It is not a substitute for professional medical advice, diagnosis, or treatment. The prescribing clinician is solely responsible for determining the appropriate dosage, monitoring, and therapy for each individual patient, considering their complete medical history and current condition. Always adhere to local prescribing guidelines and official product labeling.

Reviews

“Lithium remains the cornerstone of long-term management for my patients with classical bipolar I disorder. Its anti-suicidal efficacy is unmatched by other mood stabilizers. The necessity for monitoring is a drawback, but the clinical payoff in stability and functional recovery is profound.” – Dr. Eleanor Vance, MD, Psychiatry

“After a decade of cycling through various medications, lithium was the first agent that provided lasting stability. The blood tests and dietary awareness are a small price to pay for the clarity and balance I now experience.” – Patient M, 7 years on therapy

“While newer agents have emerged, lithium’s efficacy data and mortality benefit in severe mood disorders keep it firmly in our first-line arsenal. It demands respect for its narrow therapeutic index, but no other mood stabilizer has such a comprehensive evidence base.” – Dr. Ian Reid, PharmD, BCPP