Bipolar depression is treated with immediate-release and sustained-release pills containing lithium carbonate and other lithium salts (mania and depression).

Indications of Lithium:

• Bipolar disorder:

  • This medicine is given the green light to help people who are 7 years old or older manage their bipolar disorder.

  • It's used for treating manic episodes and for ongoing therapy to maintain stability.

• Off Label Use Lithium in Adults:

  • Dealing with bipolar depression, enhancing the impact of antidepressants, and preventing both episodic and chronic cluster headaches.

Lithium dose in adults:

Note:

• To make sure the right amount is taken, it's important to regularly check the levels of lithium in the blood and monitor how the person is responding to the treatment, considering both its effectiveness and any potential side effects.

• The oral solution of lithium citrate is concentrated. Specifically, every 5 mL contains 8 milliequivalents (mEq) of lithium ion, which is the same as the amount found in 300 milligrams of lithium carbonate immediate-release capsules or tablets.

• If the medication is well-tolerated, the prescribed amount of lithium may be reduced, and it could be given as a single dose taken before bedtime.

Lithium dose in the acute and maintenance treatment of Bipolar disorder: 

• Initial:
  • Take between 600 to 900 milligrams per day by mouth, divided into 2 to 3 separate doses.
  • The dosage can be increased gradually, for example, by 300 to 600 milligrams every 1 to 5 days, depending on how the individual responds to the treatment and their ability to tolerate it.
• usual dosage:
  • Take between 900 to 1,800 milligrams per day, dividing the total amount into 1 to 3 separate doses.

Lithium dose to augment the antidepressant effect of antidepressant: 

• Initial:
  • Start with a low dose, such as 300 milligrams taken orally once a day or 300 milligrams twice a day.
  • Depending on how well it is tolerated and the individual's response, gradually increase the dose as needed.
• usual dosage:

  • Take between 600 to 1200 milligrams daily, dividing the total amount into multiple doses throughout the day.

Lithium dose in the prevention of episodic or chronic cluster headache as an alternative agent: 

• Initial:
  • Administer between 300 to 900 milligrams per day orally, dividing the total into 1 to 3 doses.
  • Gradually increase the dosage in increments of 300 to 600 milligrams every 1 to 7 days, depending on the individual's response and ability to tolerate the medication.
  • Studies have explored doses up to 1.2 grams per day.

Lithium dose in children:

Note:

• To ensure the right dosage, it's crucial to monitor both the concentration of lithium in the blood and the clinical response, considering both effectiveness and potential side effects.

• In each 5 mL of the oral lithium solution, there are 8 milliequivalents (mEq) of lithium ion.

• This is equal to the amount of lithium found in 300 milligrams of lithium carbonate immediate-release capsules or tablets.

Lithium dose in the treatment of Bipolar disorder: 

• Immediate release:

  • For children aged 7 years and older, as well as adolescents, there is limited data for those weighing less than 20 kilograms.

  • It's important to note that dosing for individuals weighing less than 20 kilograms is estimated based on clinical experience due to the limited available data.

  • Lithium carbonate capsule or tablet:

    • Patient weight <30 kg:

      • Initially, start with 300 mg orally twice daily.

      • Increase the dose weekly by 300 mg per day increments as tolerated, until achieving the desired clinical response based on the type of therapy (acute or maintenance).

      • For acute therapy, adjust the dose to a range of 600 to 1,500 mg per day, divided into multiple doses.

      • Aim for a target serum lithium concentration between 0.8 to 1.2 milliequivalents per liter (mEq/L).

      • The manufacturer's labeling doesn't specify a maximum dose, but in trials, weight-dependent maximum daily doses were observed:

      • Patients weighing less than 23 kg: 900 mg/day
      • Patients weighing 23 kg or more: 40 mg/kg/day, with no further dose increases if serum lithium concentration reached or exceeded 1.4 mEq/L.

      • For maintenance therapy, adjust the dose to a range of 600 to 1,200 mg per day, divided into multiple doses.

      • Target a serum lithium trough concentration of 0.8 to 1 mEq/L, as tolerated.

    • Patient weight ≥30 kg:

      • Start with an initial dose of 300 mg three times daily.

      • Increase the dose by 300 mg per day increments every 3 days, as tolerated, until achieving the desired clinical response and goals based on the type of therapy (acute or maintenance).

      • For acute therapy, adjust the dose to 600 mg twice or three times daily, aiming for a target serum lithium concentration between 0.8 to 1.2 milliequivalents per liter (mEq/L).

      • The manufacturer's labeling does not specify a maximum dose, but in trials, reported doses did not exceed a maximum daily dose of 40 mg/kg, and doses were not further increased if the serum lithium concentration reached or exceeded 1.4 mEq/L.

      • For maintenance therapy, adjust the dose to a range of 300 to 600 mg twice or three times daily.

      • Target a serum lithium trough concentration of 0.8 to 1 mEq/L, as tolerated.

      • In long-term trials, doses were not further increased if the serum lithium concentration reached or exceeded 1.4 mEq/L.

    • Lithium oral solution:

      • Patient weight <30 kg:

        • Begin with an initial dose of 8 milliequivalents (mEq) twice daily.

        • Increase the dose weekly by 8 mEq increments, as tolerated, to achieve the desired clinical response and goals based on the type of therapy (acute or maintenance).

        • For acute therapy, adjust the dose to a range of 16 to 40 mEq per day, divided into multiple doses.

        • Aim for a target serum lithium concentration between 0.8 to 1.2 milliequivalents per liter (mEq/L).

        • The manufacturer's labeling does not specify a maximum dose, but in trials, weight-dependent maximum daily doses were reported:

        • Patients weighing less than 23 kg: 900 mg of lithium carbonate per day
        • Patients weighing 23 kg or more: 40 mg of lithium carbonate per kilogram per day, with no further dose increases if the serum lithium concentration reached or exceeded 1.4 mEq/L.

        • For maintenance therapy, adjust the dose to a range of 16 to 32 mEq per day, divided into multiple doses.

        • Target a serum lithium trough concentration of 0.8 to 1 mEq/L, as tolerated.

        • Doses were not further increased if the serum lithium concentration reached or exceeded 1.4 mEq/L.

      • Patient weight ≥30 kg:

        • Start with an initial dose of 8 milliequivalents (mEq) three times daily.

        • Increase the dose every 3 days by 8 mEq increments, as tolerated, to achieve the desired clinical response and goals based on the type of therapy (acute or maintenance).

        • For acute therapy, adjust the dose to 16 mEq twice or three times daily, targeting a serum lithium concentration between 0.8 to 1.2 milliequivalents per liter (mEq/L).

        • The manufacturer's labeling does not specify maximum doses, but in trials, reported doses did not exceed a maximum daily dose of 40 mg of lithium carbonate per kilogram per day.

        • Doses were not further increased if the serum lithium concentration reached or exceeded 1.4 mEq/L.

        • For maintenance therapy, adjust the dose to a range of 8 to 16 mEq twice or three times daily. Aim for a target serum lithium trough concentration of 0.8 to 1 mEq/L, as tolerated.

        • In long-term trials, doses were not further increased if the serum lithium concentration reached or exceeded 1.4 mEq/L.

• Extended release:

  • Children ≥12 years and Adolescents:

    • For weight-based dosing, the typical daily doses, given in two separate doses, are as follows:

    • For individuals weighing less than 22 kg: 600 mg/day
    • For those weighing between 22 and 41 kg: 900 mg/day
    • For those weighing more than 41 kg: 1,200 mg/day.

    • In adults, the therapy usually begins with a low dose, such as 450 mg taken twice daily or less.

    • The dosage is then increased gradually based on individual response and tolerability.

    • The typical adult dose ranges from 900 to 1,800 mg per day, administered in two divided doses.

Lithium Pregnancy Risk Category: D

• Lithium has a similar ability to cross the placenta as in the mother's blood.

• When used during pregnancy, it can lead to different issues depending on the trimester.

• In the first trimester, there's a risk of the baby developing heart malformations, particularly Ebstein anomaly.

• In later trimesters, there may be concerns about hypoglycemia and diabetes insipidus in the infant.

• Exposure to higher lithium doses during pregnancy is linked to adverse events, so it's important to closely monitor.

• If there's exposure in the early trimester, fetal echocardiography is necessary.

• Due to changes in the body during pregnancy, adjusting the lithium dose is needed to maintain stability.

• If planning to conceive, it's advisable to avoid lithium use in the first trimester.

• However, if the benefits of treating bipolar disorder outweigh the risks, continuing under the guidance of a psychiatrist is recommended.

• Throughout pregnancy, closely monitor and use the minimum effective dose.

• After organogenesis, treatment can be initiated.

• If labor is unplanned, withhold lithium for 24 to 48 hours or until delivery onset.

• The patient should be medically stable after giving birth.

Breastfeeding:

• Lithium is present in breast milk, and the serum concentrations in breastfeeding infants may be 10% to 50% higher than in their mothers.

• The drug is known to cause side effects in infants, such as hypotonia, hypothermia, cyanosis, and changes in electrocardiograms.

• It is generally recommended to avoid breastfeeding while undergoing lithium treatment.

• However, some patients may be able to continue treatment under careful consideration.

• It's crucial to monitor the mother's lithium levels and check the hydration status of breastfed infants.

• Testing the infant's serum concentrations is only necessary if there are clinical concerns.

• There haven't been studies on the long-term effects of lithium exposure through breastfeeding on a child's behavior and development.

Lithium Dose adjustment in renal disease:

• For individuals with a creatinine clearance (CrCl) ranging from 30 to 89 mL/minute, it is recommended to initiate therapy with a low dose.

• Slowly titrate the dose while closely monitoring the individual.

• However, for those with a CrCl less than 30 mL/minute, it is advised to avoid the use of the therapy altogether.

Lithium Dose adjustment in liver disease:

If there are no dosage adjustments mentioned in the labeling, it implies that the recommended dosage remains the same regardless of creatinine clearance levels.

In such cases, the standard dosage as outlined in the product labeling should be followed, and adjustments based on renal function may not be necessary.

It's always important to adhere to the specific instructions provided in the medication's official labeling or as directed by a healthcare professional.

Side effects of lithium:

• Cardiovascular:

  • Abnormal T Waves On ECG
  • Bradycardia
  • Cardiac Arrhythmia
  • Chest Tightness
  • Circulatory Shock
  • Cold Extremities
  • Edema
  • Hypotension
  • Myxedema
  • Sinus Node Dysfunction
  • Startled Response
  • Syncope

• Central Nervous System:

  • Ataxia
  • Blackout Spells
  • Cogwheel Rigidity
  • Coma
  • Confusion
  • Headache
  • Drowsiness
  • EEG Pattern Changes
  • Hypertonia
  • Fatigue
  • Hallucination
  • Hyperactive Deep Tendon Reflex
  • Involuntary Choreoathetoid Movements
  • Lethargy
  • Local Anesthesia
  • Memory Impairment
  • Loss Of Consciousness
  • Metallic Taste
  • Dystonia
  • Myasthenia Gravis
  • Pseudotumor Cerebri
  • Psychomotor Retardation
  • Reduced Intellectual Ability
  • Restlessness
  • Dizziness
  • Salty Taste
  • Sedation
  • Extrapyramidal Reaction
  • Seizure
  • Slowed Intellectual Functioning
  • Slurred Speech
  • Stupor
  • Tics
  • Vertigo
  • Worsening Of Organic Brain Syndromes

• Dermatologic:

  • Acne Vulgaris
  • Alopecia
  • Blue-Gray Skin Pigmentation
  • Dermal Ulcer
  • Dry Or Thinning Of Hair
  • Exacerbation Of Psoriasis
  • Folliculitis
  • Pruritus
  • Psoriasis
  • Skin Rash
  • Xerosis

• Endocrine & Metabolic:

  • Hypothyroidism
  • Albuminuria
  • Dehydration
  • Diabetes Insipidus
  • Euthyroid Goiter
  • Weight Loss
  • Glycosuria
  • Hypercalcemia
  • Hyperglycemia
  • Hyperparathyroidism
  • Hyperthyroidism
  • Increased Radioactive Iodine Uptake
  • Increased Thirst
  • Polydipsia
  • Weight Gain

• Gastrointestinal:

  • Dyspepsia
  • Anorexia
  • Dysgeusia
  • Excessive Salivation
  • Flatulence
  • Gastritis
  • Nausea
  • Abdominal Pain
  • Diarrhea
  • Vomiting
  • Dental Caries
  • Sialadenitis
  • Sialorrhea
  • Swelling Of Lips
  • Xerostomia

• Genitourinary:

  • Impotence
  • Incontinence
  • Oliguria

• Hematologic & Oncologic:

  • Leukocytosis

• Hypersensitivity:

  • Angioedema

• Neuromuscular & Skeletal:

  • Joint Swelling
  • Muscle Hyperirritability
  • Neuromuscular Excitability
  • Polyarthralgia
  • Tremor

• Ophthalmic:

  • Blurred Vision
  • Exophthalmos
  • Nystagmus
  • Transient Scotoma

• Otic:

  • Tinnitus

• Renal:

  • Decreased Creatinine Clearance
  • Polyuria

• Miscellaneous:

  • Fever

Contraindications to Lithium:

• Lithium should not be used in individuals with:

• Hypersensitivity to lithium or any other component in the formulation.
• Dehydration.
• Sodium depletion.
• Severe debilitation.
• Heart disease, as it is a serious condition.

• Additionally, caution is advised when using lithium concurrently with diuretics.

Warnings and precautions

• Depression in the CNS:

• Lithium can cause central nervous system (CNS) depression, which may result in a decline in both physical and mental abilities.
• Therefore, individuals taking lithium should exercise caution when engaging in activities that require focus and coordination, such as operating machinery or driving.

• Pseudotumor cerebri

• Lithium use may contribute to pseudotumor cerebri, characterized by increased intracranial pressure and papilledema (optic disc swelling).

• Undiagnosed cases may present with symptoms like blind spot enlargement, constriction of visual fields, and potential blindness due to secondary optic atrophy.

• If the symptoms are not bothersome, stopping the therapy can be considered.

• However, decisions regarding discontinuation should always be made in consultation with a healthcare professional.

• Cardiovascular disease

• Patients with pre-existing heart disease are at an increased risk of experiencing toxic effects from lithium.

• If it becomes necessary to use lithium in such cases, careful monitoring of health is essential, and caution should be exercised.

• Specifically, individuals with Brugada syndrome should not receive lithium, as it has the potential to mask the symptoms of this condition.

• If a patient suspects they may have Brugada syndrome or has risk factors such as unexplained syncope (fainting), a family history of sudden death before the age of 45, or experiences unexplained syncope after therapy, it is crucial to seek the opinion of an expert cardiologist.

• They can provide necessary insights and guidance regarding the use of lithium in such situations.

• Heart Failure:

• Lithium use has been associated with the potential to cause myocardial (heart muscle) damage.

• Fortunately, this damage is typically reversible by discontinuing the use of the drug.

• If there are concerns or symptoms related to myocardial damage, it is important to seek medical attention promptly, and healthcare professionals may advise stopping the medication as part of the treatment approach.

• Monitoring for any signs or symptoms of myocardial damage is essential for individuals taking lithium, especially those with pre-existing heart conditions.

• As always, specific medical advice should be sought from a healthcare provider regarding the management of lithium and its potential effects on the heart.
• Hypercalcemia

• The use of this therapy can result in hypercalcemia, either with or without hyperparathyroidism.

• Although the dose itself doesn't impact the risk, the likelihood is higher in older individuals and females.

• Serum calcium levels may be slightly elevated, exceeding 15 mg/dL on average.

• Parathyroid hormone (PTH) levels can range from normal to elevated, sometimes significantly above the upper limit.

• Magnesium levels are often increased, while serum phosphate levels may be normal or low.

• Regular monitoring of calcium and PTH levels is crucial.

• If symptoms of hypercalcemia develop, such as fatigue, weakness, or constipation, therapy should be discontinued.

• Following withdrawal, serum calcium levels should be monitored weekly for one month to ensure a return to baseline.

• It's important to note that while stopping the therapy can reverse these changes, there's a possibility of sustained hypercalcemia or enlargement of the parathyroid glands.

• Regular medical supervision and follow-up are advised in such cases.

• Thyroid disease:

• The therapy may lead to hypothyroidism, so it's crucial to exercise caution when treating patients who already have thyroid dysfunction.
• Regular monitoring of thyroid function is important to detect any changes and adjust the treatment plan accordingly.
• Patients with pre-existing thyroid conditions should be closely supervised during therapy to ensure their thyroid function remains within a normal range.
• If signs of hypothyroidism develop, appropriate interventions and adjustments to the treatment plan may be necessary.
• Consulting with a healthcare professional is essential for managing thyroid function in patients undergoing this therapy.

• Hypothyroidism

  • Hypothyroidism may develop within six to 18 months after starting treatment. 
  • Hypothyroidism should not be stopped if symptoms of bipolar disorder have been well controlled.
  • Hypothyroidism can be more dangerous in females.

• Renal impairment

  • People with serious kidney problems are more likely to get poisoned by lithium, so it's better to avoid using it.
  • If you really need to use it, be super careful and keep a close eye on things with careful monitoring.

• Effects on the renal system:

  • Using lithium for a long time might cause a condition called nephrogenic diabetes insipidus.
  • Luckily, this condition can often be reversed when you stop taking lithium.
  • People with bipolar disorder who haven't used lithium before might experience changes in the kidney, like fibrosis and atrophy, especially with prolonged treatment.
  • It's not clear if these changes affect kidney function or if they're directly linked to lithium use.
  • To make sure you stay hydrated, it's important to regularly check and reassess your kidney health while using lithium.
  • During lithium treatment, you might pee more (polyuria). Lowering the daily dose could reduce this increase in urine output.

• Serotonin syndrome

  • Taking lithium can potentially cause a serious condition called serotonin syndrome, which can be deadly.
  • Serotonin syndrome may show up with changes in mental state, like being agitated or hallucinating, along with physical symptoms such as rapid heartbeat, dizziness, and muscle changes.
  • If these symptoms happen, it's crucial to get help right away and start supportive therapy.
  • The risk of serotonin syndrome goes up when lithium is used with certain other medications that affect serotonin levels, like SSRIs, SNRIs, and some pain medications.

• Dehydration

  • People who lose a lot of fluids or have low sodium levels are more likely to experience harmful effects from lithium.
  • In such cases, it's important to be cautious and keep a close watch with regular check-ups.
  • If someone has trouble tolerating lithium, signs like diarrhea or excessive sweating may show up.
  • These should be addressed by lowering the dose or stopping the medication, and adding extra fluids and salt under a doctor's guidance.
  • If there's an infection causing a fever, the lithium dose might need to be reduced or stopped.

• Suicidal thoughts and depression:

  • People who are at a high risk of attempting suicide using drugs need to be careful with lithium because it has a very small margin of safety.

Monitoring parameters:

• Keep an eye on weight regularly.
• Check blood counts, kidney function, and electrolyte levels at the beginning and as needed.
• For kids, kidney function tests are especially important.
• Monitor electrolytes like sodium and calcium periodically.
• Check thyroid function a couple of times in the first 6 months and then annually for stable patients.
• If a woman is not sterile, do a pregnancy test at the beginning.
• Watch out for excessive urination.
• Patients over 40 or with heart risk factors should have a baseline ECG.
• Check lithium levels twice a week until stable, then less frequently as needed.

How to administer Lithium?

• Take it by mouth with meals to reduce stomach discomfort.
• If it's an extended-release tablet, swallow it whole without crushing or chewing.

Mechanism of action of Lithium:

• We're not exactly sure how it works for mood disorders.
• It's believed to affect how cells in nerves and muscles transport certain particles across their membranes.
• This, in turn, impacts the levels of norepinephrine and how certain cellular messaging systems work.
• It helps clear out excess glutamate and blocks a specific enzyme involved in cell death.
• There are increased levels of a protective protein called Bcl-2.
• It also boosts the production of neurotrophic factors like brain-derived neurotrophic factor, which helps protect the brain.

Absorption:

• Rapid and complete.

Protein binding:

• Not protein bound.

Metabolism:

• Not metabolized.

Bioavailability:

• 80% to 100%.

Half-life elimination:

• For kids aged 7 to 17, it takes about 27 hours for the substance to leave the body.
• For adults, it typically ranges from 18 to 36 hours, but it might take longer (around 28.5 hours) for elderly individuals.

Time to peak serum concentration:

• Immediate release takes around 0.5 to 3 hours to start working.
• Extended-release starts working in 2 to 6 hours.
• The solution form works relatively quickly, usually in 15 to 60 minutes.

Excretion:

• It mainly leaves the body through urine without being changed.
• A tiny amount is also expelled in sweat, saliva, and feces.

Clearance:

• About 80% of the filtered lithium gets reabsorbed in the proximal convoluted tubules of the kidneys.
• This reabsorption decreases in elderly individuals due to age-related declines in kidney function.

International Brands of Lithium:

• Lithobid
• APO-Lithium Carbonate; Carbolith
• DOM-Lithium Carbonate
• Lithane
• Lithmax
• PMS-Lithium Carbonate
• PMS-Lithium Citrate
• Calith
• Camcolit
• Camcolite
• Carbolim
• Carbolit
• Carbolithium
• Carlit
• Ceglution
• Contemnol
• Eskalith
• Frimania
• Hynorex Retard
• Hypnolith
• Karlit
• Kilonum
• Licab
• Licarb
• Licarbium
• Limas
• Liskonum
• Litarex
• Litcab
• Lithan
• Litheum 300
• Lithicarb
• Lithicarb FC
• Lithin SR
• Lithionit
• Lithium Carbonicum
• Lithiumkarbonat ”Oba”
• Lithocap
• Lithosun SR
• Litiam ER
• Liticarb
• Litij-karbonat
• Litiumkarbonat ”Dak”
• Lito
• Litocarb
• Manicarb SR
• Maniprex
• Microlit
• Milithin
• Neurolepsin
• Plenur
• Priadel
• Priadel Retard
• Prianil C.R.
• Quilonium-R
• Quilonorm
• Quilonorm Retardtabletten
• Quilonum Retard
• Quilonum retard
• Quilonum SR
• Sicolitio
• Teralithe
• Theralite

Lithium Tablets Brands in Pakistan: