- 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 and reduces the risk of suicide in patients with major depressive disorder. The specific mechanism by which lithium acts to stabilize mood is still 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 of lithium use 
Side effects related to lithium use can occur even at therapeutic levels .
- 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
- Treatment: amiloride
- lithium-associated nephropathy) (
- Skin: acne, psoriasis
Lithium toxicity 
- Because lithium has a very narrow therapeutic window, patients require frequent monitoring.
Definition: serum lithium levels > 1.5 mEq/L (1.5–2.0 mmol/L)
- Acute toxicity: seen in patients with a low baseline level of lithium (not on regular therapy) who have acutely taken a large dose (e.g., suicide attempt)
- Acute on chronic toxicity: seen in patients receiving long-term lithium treatment who have taken a larger dose acutely
- Chronic toxicity: seen in patients receiving long-term lithium; treatment; usually occurs due to a recent dose increase, new renal impairment, or newly introduced therapy that exacerbates lithium effects
Risk factors 
- Renal impairment
- Medications that can precipitate lithium toxicity by increasing renal absorption of lithium
- Low effective circulating volume (e.g., due to dehydration, loop diuretic use , cirrhosis, congestive heart failure)
- Other medications: tetracyclines, cyclosporine
- Low-sodium diet or increased perspiration
- Acute toxicity and acute on chronic toxicity
- Chronic toxicity
- Renal: acute kidney injury
- Endocrine: myxedema coma
- Psychiatric: apathy, psychomotor impairment
- 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.
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
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 expected 4–5 days after initiation or a change in dose.
- 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