- 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
- Discontinue lithium
- Hydration with isotonic fluid and electrolyte correction to promote lithium clearance
- 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.