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
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.
- Fine tremor
- Muscle weakness
- ECG changes: T-wave depressions (most common), , repolarization abnormalities
- Sinus node dysfunction (most commonly sinus bradycardia)
- (often subclinical)
- Lithium-induced hyperparathyroidism
- third trimester of pregnancy (particularly in second and )
- Pathophysiology: lithium interferes with ADH signaling → ↓ aquaporins (water channels) on the collecting duct cell's surface → ↓ water molecules are reabsorbed and kidneys are unable to concentrate urine → ↑ free water excretion
- Clinical features: polyuria, nocturia, and polydipsia → ↑ risk of dehydration and subsequent lithium toxicity
- (lithium-associated nephropathy)
Treatment of adverse effects 
- 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 
- Toxic effects occur at serum levels > 1.5 mEq/L. 
- For details and management, see “Lithium poisoning.”
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 
- Concurrent diuretic use
- Dehydration, sodium depletion
- Desired pregnancy/pregnancy: lithium can freely cross the placental barrier, inevitably resulting in fetal lithium exposure
- ↑ Risk of miscarriage and neonatal complications (e.g., longer duration of hospital stays, higher rate of CNS and neuromuscular complications) 
- Teratogenicity; (especially in the first trimester): ↑ risk of cardiovascular malformations (in particular )
- If lithium is needed during pregnancy, aim for the minimum effective dose and monitor serum levels regularly.
- LARCs are generally the preferred method of contraception because they are easy to use and have low failure rates. 
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.