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Lithium interacts with a number of neurotransmitters and receptors in the CNS, decreasing norepinephrine (noradrenaline) release and increasing serotonin synthesis. The specific biochemical mechanism of lithium action in mania is unknown.


Lithium is used as mood-stabilizing drug, primarily in the treatment of bipolar disorder, where they have a role in treating depression and, particularly, of mania, both acutely and in the long term. As a mood stabilizer, lithium is probably more effective in preventing mania than in preventing depression, but it does reduce the risk of suicide in people with bipolar disorder. In depression alone (unipolar disorder), lithium can be used to augment other antidepressants.

  • Lithium is a first-line agent for the acute and maintenance treatment of mania and hypomania.
  • Lithium is also first-line for the maintenance treatment of mixed episodes and is useful as adjunctive treatment in depressive episodes.

[edit] DOSAGE

The required dosage is slightly less than the toxic level, requiring blood levels of lithium to be monitored closely during treatment. Serum lithium concentrations are usually in the 0.5–1.2 mmol/l range in well-controlled people, but may increase to 1.8–2.5 mmol/l in those who accumulate the drug over time and to 3–10 mmol/l in acute overdose. If toxicity occurs, lithium should be immediately discontinued, the patient should be properly hydrated, stomach contents should be emptied with gastric lavage, and if severe toxicity occurs (level ≥ 3 mEq/L), hemodialysis may be indicated.

Lithium is eliminated primarily through the kidneys. It is filtered by the glomeruli in the kidneys and is also cleared by renal tubular reabsorption. Changes in renal function can significantly affect the clearance of lithium.

Patients are generally started on 300 mg two to three times daily of lithium and titrated up by 300 mg increments as needed to achieve therapeutic effects and minimize toxicity. Patient specific factors should be considered when deciding the appropriate initial dose, such as age, weight , and renal function.

Serum concentrations may be monitored 3 days after initiation therapy or changing doses. Levels should be obtained 12 hr after the dose, usual ly in the morning before the first dose of the day.

Clinical response may be seen within 2 weeks after lithium initiation for the treatment of acute mania. When used in depression, responses may not occur for 4-6 weeks.


Lithium has an absolute contraindication in patients experiencing acute renal failure or women in their first trimester of pregnancy.

Lithium has the following relative contraindications: renal impairment, cardiovascular disease, dehydration, pregnancy, seizure disorder , and thyroid disease.


Those who use lithium should receive regular serum level tests and should monitor thyroid and kidney function for abnormalities, as it interferes with the regulation of sodium and water levels in the body, and can cause dehydration due to lithium inhibition of the action of antidiuretic hormone, which normally enables the kidney to reabsorb water from urine. This causes an inability to concentrate urine, leading to consequent loss of body water and thirst.


  • Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease renal blood flow and decrease lithium clearance, resulting in increased lithium concentrations.
  • Use of lithium with antipsychotics or benzodiazepines may increase the risk for CNS toxicity, especially if used together long term.
  • Use of lithium with medications that can increase 5- HT may cause serotonin syndrome.



Early Onset: Gastrointestinal upset, nausea, polydipsia (excessive thirst), nocturia, dry mouth, hand tremor, leukocytosis (leukocyte count above the normal range), polyuria.

Long-Term Use: weight gain, altered taste, decreased libido, hypothyroidism, rash, acne, psoriasis, alopecia.

Toxicity: Severe drowsiness, coarse hand tremor, muscle twitching, seizures, choreoathetosis, vomiting, confusion, vertigo.