Lithium carbonate

Usage

• Lithium carbonate is primarily prescribed for the treatment of bipolar disorder, including acute manic or mixed episodes and maintenance therapy to prevent relapse. It can also be used to augment antidepressants in treatment-resistant depression.
• Pharmacological classification: Mood stabilizer.
• Mechanism of action: While the precise mechanism is not fully understood, lithium is thought to modulate neuronal excitability by influencing intracellular signaling pathways involving inositol phosphate metabolism and neurotransmitter systems, particularly dopamine and serotonin.

Alternate Names

• Lithium citrate (liquid formulation)
• Brand Names: Eskalith, Lithobid, Priadel, Camcolit, Liskonum, Li-Liquid

How It Works

• Pharmacodynamics: Lithium exerts its therapeutic effect by altering the balance of excitatory and inhibitory neurotransmission, stabilizing mood swings associated with bipolar disorder. The exact mechanism remains incompletely elucidated, but it appears to involve multiple pathways including:

  • Inhibition of inositol monophosphatase, affecting the recycling of inositol, a key component of second messenger systems.
  • Modulation of neurotransmitter systems, such as serotonin, dopamine, and glutamate, though the precise nature of these interactions is complex.
  • Neuroprotective effects, possibly through modulation of signaling pathways related to apoptosis and oxidative stress.

• Pharmacokinetics:

  • Absorption: Almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 1-3 hours for standard formulations and 4-4.5 hours for slow/extended-release formulations.
  • Metabolism: Not metabolized.
  • Elimination: Primarily excreted unchanged by the kidneys. Renal clearance is influenced by factors like sodium intake and hydration status.

• Mode of action (cellular/molecular): Lithium influences multiple intracellular signaling pathways, including:

  • Inhibition of glycogen synthase kinase-3 (GSK-3), implicated in various cellular processes and potentially contributing to its mood-stabilizing and neuroprotective effects.
  • Modulation of intracellular calcium levels and protein kinase C activity.

• Elimination pathways: Renal excretion.

Dosage

Standard Dosage

Adults:

• Acute mania: Initially, 900-1800 mg/day of lithium carbonate in divided doses, adjusted based on serum levels and clinical response. Target serum lithium concentration: 0.8-1.2 mEq/L.
• Maintenance: 900-1200 mg/day in divided doses, titrated to maintain serum lithium concentrations of 0.6-1.0 mEq/L.
• Extended-release formulations: 900 mg twice daily or 600 mg three times daily for acute mania and 600-1200 mg/day for maintenance.

Children (7-17 years):

• Dosing is individualized based on weight, age, clinical response, and serum levels.
• Initiate with lower doses and titrate upward based on tolerability and efficacy. Target serum lithium concentration is generally similar to adults.
• Children younger than 7 years: Use is generally not recommended.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously due to age-related changes in renal function and increased sensitivity to lithium. Serum levels below 1.0 mEq/L may be sufficient.
• Patients with Renal Impairment: Dose reduction is necessary based on the degree of impairment. Close monitoring of serum levels is essential.
• Patients with Hepatic Dysfunction: No specific dose adjustments are usually required, as lithium is not metabolized by the liver.
• Patients with Comorbid Conditions: Careful consideration is needed for patients with cardiovascular disease, thyroid disorders, and other conditions that may interact with lithium.

Clinical Use Cases

Lithium is not typically indicated for use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its primary role is in the management of bipolar disorder.

Dosage Adjustments

• Dose adjustments are based on serum lithium levels, clinical response, and tolerability.
• Renal or hepatic dysfunction, metabolic disorders, and drug interactions can necessitate dosage modifications.
• Regular monitoring of serum lithium levels is crucial, especially during initial titration and when there are changes in patient’s clinical status or concurrent medications.

Side Effects

Common Side Effects

• Fine tremor
• Nausea, diarrhea
• Polyuria, polydipsia
• Weight gain
• Cognitive effects (e.g., difficulty concentrating)

Rare but Serious Side Effects

• Lithium toxicity (serum levels >1.5 mEq/L), characterized by coarse tremor, confusion, ataxia, seizures, cardiac arrhythmias, and even coma.
• Renal dysfunction
• Thyroid abnormalities
• Cardiac effects (e.g., bradycardia, EKG changes)

Long-Term Effects

• Renal impairment (e.g., nephrogenic diabetes insipidus)
• Thyroid dysfunction (hypothyroidism or hyperthyroidism)
• Hyperparathyroidism
• Cardiovascular effects

Adverse Drug Reactions (ADR)

• Lithium toxicity
• Serotonin syndrome (when combined with serotonergic drugs)
• Neuroleptic malignant syndrome (rare)

Contraindications

• Significant renal or cardiovascular disease
• Severe dehydration or sodium depletion
• Hypersensitivity to lithium
• Brugada syndrome or family history of Brugada syndrome

Drug Interactions

• Diuretics: Increased lithium levels due to sodium depletion.
• NSAIDs: Increased lithium levels.
• ACE inhibitors and ARBs: Increased lithium levels.
• Antipsychotics: Increased risk of neurotoxicity.
• Serotonergic drugs: Increased risk of serotonin syndrome.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: D. Lithium is known to cross the placenta and can increase the risk of cardiac malformations, particularly Ebstein’s anomaly, when used during the first trimester.
• Monitor lithium levels closely during pregnancy. Dosage may need to be adjusted.
• Breastfeeding: Lithium is excreted in breast milk. While breastfeeding is generally not recommended, it may be possible in some cases with careful monitoring of infant lithium levels and assessment for potential adverse effects.

Drug Profile Summary

• Mechanism of Action: Mood stabilization through modulation of neuronal excitability and intracellular signaling pathways.
• Side Effects: Tremor, nausea, polyuria, weight gain, cognitive effects, lithium toxicity (serious).
• Contraindications: Severe renal/cardiovascular disease, dehydration, hypersensitivity.
• Drug Interactions: Diuretics, NSAIDs, ACE inhibitors, antipsychotics, serotonergic drugs.
• Pregnancy & Breastfeeding: Category D; use with caution. Monitor infant closely if breastfeeding.
• Dosage: Individualized based on indication, age, renal function, and serum levels.
• Monitoring Parameters: Serum lithium levels, renal function, thyroid function, electrolytes, EKG.

Popular Combinations

• Lithium is often combined with antipsychotics, particularly atypical antipsychotics, for the treatment of acute mania or mixed episodes.
• It may also be used with antidepressants in treatment-resistant depression.

Precautions

• General Precautions: Monitor renal, thyroid, and cardiac function. Evaluate electrolyte levels regularly. Assess for dehydration and sodium depletion.
• Specific Populations: Careful monitoring is essential during pregnancy and breastfeeding. Elderly patients require lower initial doses.
• Lifestyle Considerations: Maintain adequate hydration and stable sodium intake. Avoid abrupt discontinuation.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Lithium carbonate?

A: Dosing is individualized. Adults: Acute mania: 900-1800 mg/day; maintenance: 900-1200 mg/day. Children: Individualized based on weight and serum levels. Elderly: Start low and titrate slowly.

Q2: How is lithium toxicity managed?

A: Stop lithium immediately. Supportive care, including hydration, correction of electrolyte imbalances, and management of seizures or cardiac arrhythmias. Hemodialysis may be necessary in severe cases.

Q3: What are the key monitoring parameters for patients on lithium?

A: Serum lithium levels (regularly), renal function tests (creatinine, eGFR), thyroid function tests (TSH, T4, T3), electrolytes, and EKG.

Q4: Can lithium be used during pregnancy?

A: Lithium is a category D drug. It can be used during pregnancy if the benefits outweigh the risks, but it carries a risk of fetal cardiac malformations, especially in the first trimester. Close monitoring of lithium levels and fetal echocardiography are essential.

Q5: What are the common drug interactions with lithium?

A: Diuretics, NSAIDs, ACE inhibitors, ARBs, antipsychotics, and serotonergic drugs can interact with lithium, potentially increasing serum levels and the risk of toxicity.

Q6: What are the long-term side effects of lithium therapy?

A: Long-term use can lead to renal impairment (e.g., nephrogenic diabetes insipidus), thyroid dysfunction, and hyperparathyroidism.

Q7: How should lithium be discontinued?

A: Lithium should be tapered gradually to minimize the risk of relapse. Abrupt discontinuation can precipitate manic episodes.

Q8: What are the early signs of lithium toxicity?

A: Coarse tremor, confusion, ataxia, vomiting, diarrhea, and slurred speech are early signs of lithium toxicity.

Q9: What is the difference between lithium carbonate and lithium citrate?

A: Lithium carbonate is available in tablet form (including extended-release formulations), while lithium citrate is a liquid formulation. Lithium citrate is generally reserved for patients who have difficulty swallowing tablets.

Q10: What patient education is essential for those starting lithium?

A: Explain the importance of medication adherence, regular monitoring of serum levels, maintaining adequate hydration, avoiding abrupt discontinuation, and reporting any unusual symptoms promptly. Discuss potential side effects and drug interactions.