Lithium, Lithane®

Brand name

  • Lithane®

Drug Class

  • Antimanic agent

Preparations

  • Capsules: 150 mg; 300 mg

Indications

  • Acute manic episodes
  • Manic- depressive disorders
  • Maintenance therapy: preventing or diminishing the frequency of subsequent relapses in bipolar manic-depressive patients (with a strong history of mania).

Pharmacology

Mechanism of action:

  1. Lithium alters sodium transport in nerve and muscle cells,
  2. Shift toward intraneuronal metabolism of catecholamines
  3. Inhibitory action on the intracellular formation of cyclic AMP

Pharmacokinetics:

  1. Absorption: from the gastrointestinal (GI) tract – Peak Plasma Concentration: 2-4 hours after consumption.
  2. Distribution: Slowly Crosses the blood brain barrier.
  3. Elimination and excretion: 99% Urine, 1% Feces
  4. Lithium plasma Half life: 24 hours
  5. Attention: concentration of sodium will increase lithium reabsorption and might result in retention or intoxication.

Dosing

Acute Mania:

  • Should be based primarily on the patient’s clinical condition
  • Initially 600 and 900 mg/day, reaching a level of 1200 to 1800 mg in three divided doses on the second
  • Serum Li-Carbonate level Between 1 and 1.5 mmol/L

Mania (Long term control):

  • Between 600 and 1200 mg/day divided in three doses
  • Serum levels between 0.6 and 1.2 mmol/L (Less than 1.5 mmol/L)
  • No satisfactory response in 14 days = discontinue Li Carbonate therapy!

Drug Interactions

  • Sodium Bicarbonate (NaHco3):
    • Decreased lithium effects
  • Potassium Iodide:
    • Hypothyroidic and goitrogenic effects
  • Haloperidol:
    • Combined therapy should be monitored closely for early evidence of neurologic toxicity (Encephalopathic syndrome) and discontinued promptly.
  • Diuretics and Angiotensin Converting Enzyme (ACE) Inhibitors: (Na Loss)
    • If such combinations lithium dosage may need to be decreased
  • Phenothiazines:
    • Increases in red cell uptake of lithium
  • Chlorpromazine:
    • Increases in renal lithium excretion
  • Non-Steroidal Anti-Inflammatory Drugs (NSAID)s:
    • Increase significantly, steady state plasma lithium levels
  • Selective Serotonin Reuptake Inhibitors (SSRI) Drugs:
    • Enhance the serotonergic effects of SSRI drugs
    • Fluvoxamine: convulsions
    • Fluoxetine: Increased and decreased lithium levels
    • Sertraline: Tremors
  • Carbamazepine:
    • Neurotoxicity (in the absence of toxic serum lithium concentrations)
  • Neuromuscular Blocking Agents: (eg: Succinylcholine, Pancuronium)
    • In chronic lithium therapy: Long duration of action of these drugs
  • Theophylline:
    • In chronic lithium therapy: Long duration of action of these drugs
    • Enhances renal clearance of lithium = Reduce serum lithium concentrations
    • Caution: Discontinuation of theophylline on chronic lithium therapy = Excessive lithium response (Toxicity)
  • Calcium Channel Blockers (CCBs):
    •  Neurotoxicity
  • Propranolol:
    • Increase lithium serum concentrations
    • Bradycardia
  • Tricyclic Antidepressants:
    • Lower the seizure threshold
  • Diazepam:
    • Serious hypothermia
  • Sodium Chloride:
    • Developing symptoms of lithium toxicity.
  • Urea:
    • Enhance renal excretion of lithium = Reduced lithium serum concentrations.

Adverse Effects

Most frequent side effects are the initial post-absorptive symptoms:

  • Gastrointestinal discomfort (earliest): Anorexia, nausea, vomiting, diarrhea, abdominal pain, and weight loss.
  • Nausea
  • Vertigo
  • Muscle weakness
  • Dazed feeling
  • Mostly associated with a rapid rise in serum lithium levels

More common and persistent adverse reactions:

  • Fine tremor of the hands
  • Fatigue
  • Thirst
  • Polyuria: Nephrogenic Diabetes Inspedius (polyuria-Polydipsia

Other side effects: (Less frequent)

  • Metallic taste
  • Fasciculation
  • Twitching, especially of facial muscles and clonic movements of the limbs
  • CNS & PNS& Autonom: Urinary and fecal incontinence, blurred vision, dry mouth
  • Seizures
  • Somnolence
  • Cardiovascular: Arrhythmia, hypotension, reversible flattening isoelectricity or inversion of T-waves in ECG.
  • Thyroid Abnormalities: Euthyroid goiter and/or hypothyroidism (including myxedema)
  • Hypersensitivity
  • Hematologic: Anemia, leukopenia and leukocytosis.

Contraindications

  1. Significant cardiovascular or renal disease.
  2. Severe debilitation state
  3. Severe dehydration
  4. Sodium depletion, brain damage, and in conditions requiring low sodium intake
  5. Children < 12 years of age

Pregnancy and Breastfeeding

Pregnancy: Increase significantly, steady state plasma lithium levels

Lactation: Nursing should not be undertaken

Precautions

Screen initially & periodically:

  1. BUN (Blood Urea Nitrogen)
  2. Serum Cr (Creatinin)
  3. 24 hour urine volume
  4. Serum Na
  5. Serum K
  6. FBS (Fasting Blood sugar)
  7. TSH (Thyroid stimulating hormone)
  8. ECG (Electrocardiography)
  9. Serum Calcium
  10. Record of weight
  11. Urine Specific gravity

Low therapeutic index:

  • Therapeutic plasma level relatively close to toxic level (Geriatrics more susceptible)
  • Li Plasma level: Max= 1.5-2 mmol/L
  • Serum lithium levels in uncomplicated cases receiving maintenance therapy should be monitored at least every 2 months.
  • Signs and symptoms of Li-Carbonate intoxication:
    1. Fatigue,
    2. Muscular weakness,
    3. Incoordination,
    4. Drowsiness,
    5. Coarse tremors,
    6. Diarrhea
    7. Vomiting
  • Li-Carbonate is mainly excreted by kidneys, therefore Adequate renal function + Adequate salt and fluid intake (2500 to 3000 mL a day) are essential.

Frequent serum Li- Carbonate determinations are required especially during the initial period of treatment:

  • First blood sample blood sample: Before the patient has had his/her first lithium dose.
  • Second blood sample blood sample: 9 – 12 hours after his/her last dose of drug.
  • If > 2mmol/L = Discontinue
  • Three times weekly during the initial period of administration
  • If >1.5- 2 mmol/L = Discontinue for 24 hours and recheck the Li-Carbonate plasma level, if normal, restart.
  • Decrease tolerance: When the acute attack subsides, reduce the dose rapidly in order to produce serum lithium levels no higher than between 0.6 and 1.2 mmol/L

In case of nephrogenic diabetes insipidus, with polyuria and polydipsia:

  • Avoid dehydration with resulting lithium retention and toxicity
  • Mostly reversible

Lithium plus Haloperidol: Combined therapy should be monitored closely for early evidence of neurologic toxicity (Encephalopathic syndrome) and discontinued promptly:

  • Encephalopathic syndrome characteristics:
  1. Weakness
  2. Lethargy
  3. Fever
  4. Tremulousness
  5. Confusion
  6. Extrapyramidal symptoms
  7. Leukocytosis, elevated serum enzymes
  8. Elevated BUN and FBS

Patients on Li- Carbonate with:

  • Cardiovascular diseases:
    • Observed carefully for signs of arrhythmias.
    • Initial & Periodic ECG
  • Thyroid Disorder:
    • Initially & periodically TSH
    • Exam thyroid before initial Li therapy for non-toxic nodular goiter

Discontinuation of therapy:

  • No withdrawal symptoms/ Rebound phenomenon (almost)

Li Carbonate Overdose management general steps: (No antidote)

  1. Lavage
  2. Correction of fluid and electrolyte imbalance
  3. Regulation of kidney function
  4. Hemodialysis

Section

This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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