- Clinical science
Lithium is a psychiatric medication used primarily as a first-line therapy for bipolar disorder. It is also used in treatment-resistant depression to augment antidepressants. The specific mechanism by which lithium acts to stabilize mood is not definitively known, but it is thought to be due to inhibition of the phosphoinositol cascade. Common side effects include gastrointestinal distress (nausea, diarrhea), polyuria, polydipsia, and tremor. Lithium therapy has a very narrow therapeutic index; frequent monitoring is therefore required to prevent toxicity.
While the mechanism of action has not been definitively established, inhibition of the phosphoinositol cascade is thought to result in mood stabilization.
Side effects occur at therapeutic levels (0.8-1.2 mEq/L) but tend to be more severe at peak serum concentration of the drug.
- Fine tremor
- Nausea, diarrhea
- Polyuria, polydipsia
- Weight gain
- Worsens psoriasis
- Muscle weakness
- Dry oral mucosa
- Hair thinning
- ECG changes: T-wave depressions (most common), , repolarization abnormalities
- Sinus node dysfunction (most commonly sinus bradycardia)
- (particularly in second and third trimester of pregnancy)
- Hyperparathyroidism causing hypercalcemia
- Pathophysiology: lithium interferes with ADH signaling → reduces aquaporins (water channels) on the collecting duct cell's surface → fewer water molecules are reabsorbed and kidneys are unable to concentrate urine → increased free water excretion
- Clinical features: polyuria, nocturia, and polydipsia → increased risk of dehydration and subsequent lithium toxicity
- Treatment: amiloride
- (lithium-associated nephropathy)
- Teratogenicity: cardiac malformations, in particular (0.1% risk)
- Toxicity occurs at serum levels >1.5 mEq/L.
- Increase in dosage
- Renal impairment from any cause
- Low effective circulating volume (e.g., due to dehydration, loop diuretic use , cirrhosis, congestive heart failure)
- Medications that can precipitate lithium toxicity by increasing renal absorption of lithium
- Other medications: tetracyclines, cyclosporine
- Acute renal failure
|Acute toxicity|| |
|Acute on chronic toxicity|| || |
|Chronic toxicity|| |
- Discontinue lithium
- Hydration with isotonic fluid and electrolyte correction to promote lithium clearance
- First-line treatment for severe lithium toxicity
- Indications 
- Serum lithium concentration > 5.0 mEq/L
- Serum lithium concentration > 4.0 mEq/L with kidney dysfunction
- Altered mental status, seizures, and/or life-threatening arrhythmias
- Expected time required to reduce serum lithium concentration to < 1.0 mEq/L is > 36 hours
- Hemodialysis should be continued until serum lithium concentration is < 1.0 mEq/L or for a minimum of 6 hours (if the serum lithium concentration cannot be measured).
- Ventilatory support, if required
- Whole bowel irrigation with polyethylene glycol can also be considered.
- Activated charcoal does NOT prevent the absorption of lithium.
Monitoring serum levels of lithium is important because of its narrow therapeutic window (0.8–1.2 mEq/L).
We list the most important adverse effects. The selection is not exhaustive.
- Advanced renal failure (creatinine clearance < 30 mL/minute)
- Severe cardiovascular disease
- Relative contraindications
Alternative maintenance treatment options for bipolar disorder include valproate, quetiapine, and lamotrigine. Valproate, carbamazepine, and antipsychotics can be used for treatment of acute mania and hypomania.
We list the most important contraindications. The selection is not exhaustive.
Excreted almost entirely via the kidneys; most of the lithium filtered by the kidneys is reabsorbed at the proximal convoluted tubule via sodium channels. 
- Monitoring serum levels of lithium is important because of its narrow therapeutic window.
- Steady state serum levels are usually reached 4–5 days after initiation or a change in dosage.
- Due to its slow onset of action, effects are expected 1–2 weeks after initiation of treatment.
- Optimal range of lithium serum level: 0.8 mmol/L–1.2 mmol/L for acute management and long-term maintenance
How to implement lithium monitoring
- Lithium serum level: 5–7 days after initiating treatment or a dose change, or every 6–12 months for patients on steady doses
- Half-life : 12–24 hours → A blood sample for serum level monitoring should be taken 12 hours after the last dose.
- Suggested dosage: lithium 2–3 times daily