- 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.
- Mechanism of action: While the mechanism of action has not been definitively established, inhibition of the phosphoinositol cascade is thought to result in mood stabilization.
- Steady state: usually reached 4–5 days after initiation or a change in dosage
General adverse effects 
Adverse effects occur at therapeutic levels (0.4–1.0 mEq/L) but tend to be more severe at peak serum concentration of the drug. 
- 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
- (lithium-associated nephropathy)
- Teratogenicity: cardiac malformations, in particular
Lithium toxicity 
Toxicity occurs at serum levels > 1.5 mEq/L.
- Increase in dosage (lithium has a narrow therapeutic window)
- 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, cyclosporines
- Acute renal failure
- Reassurance, avoidance of exacerbating factors (e.g., caffeine, stress), and follow-up
- Dosage adjustment
- Use of short-acting lithium preparations, divided doses, or a different lithium salt (e.g., citrate instead of carbonate)
- Reducing the total daily dose of lithium if serum lithium concentration is close to the upper limit of the therapeutic range
- Tremor: beta blockers (e.g., propranolol) if persistent or severe tremor 
- Nephrogenic diabetes insipidus: amiloride 
- Discontinuation of lithium
- Hydration with isotonic fluid (0.9% NaCl solution) and electrolyte correction to promote lithium clearance
Hemodialysis: first-line treatment for severe lithium toxicity
- Indications 
- 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.
We list the most important adverse effects. The selection is not exhaustive.
- Absolute contraindications 
- Relative contraindications
Alternative maintenance treatment options for bipolar disorder include lamotrigine, valproate, and carbamazepine. Valproate and antipsychotics (e.g., olanzepine, quetiapine) can be used for treatment of acute mania and hypomania.
We list the most important contraindications. The selection is not exhaustive.