lithium
Class: Mood StabilizerFDA Indications: Acute Mania
Off-Label Use: Bipolar Disorder Maintenance, Augmentation Of Antidepressants, Migraines, Graves' Disease, Cluster Headaches, Neutropenia, SIADH
Prescribing
Forms: 150, 300, 600mg tablet; 300, 450mg Extended Release tablet; 8 mEq/5 mL solnDose Range: 900-1800 mg/day
Starting: Start at 300 mg bid or tid and ↑ dose as tolerated to target serum levels
Stopping: Prudent to decrease by 300 mg q 2-4 weeks; abrupt discontinuation (≥2 weeks) may precipitate episode
Monitoring: Serum Li+—target range 0.6-1.2 mEq/L for bipolar mania and 0.4-0.8 mEq/L for augmentation
Precautions
Contraindications: Severe cardiovascular or renal disease, severe debilitation, dehydration, sodium depletion, concurrent use with diureticsSerious Side Effects: Li+ toxicity
| mmol/L | s/sx |
| 1.0-1.5 | ↓ concentration, lethargy, tremor, slurred speech, nausea |
| 1.6-2.5 | confusion, disorientation, drowsiness, unsteady gait, dysarthria, muscle fasciculations |
| >2.5 | impaired consciousness → coma, delirium, ataxia, ↓ renal function & convulsions |
Possible Risk of TdP, Drugs to Avoid in Congenital Long QT
Side Effects: tremor, polyuria, polydipsia, hypothyroidism, ↓ renal function, weight gain, cognitive slowing, leukocytosis, alopecia, ECG Δ's , diarrhea, nausea, vomiting, dysgeusia, xerostomia, visual changes, hyperparathyroidism, hypercalcemia
Pharmacodynamics
1° MOA: Thought to alter cation transport across cell membranes in nerve and muscle cells, influence the reuptake of 5-HT and/or NE, and inhibit 2nd messenger systems involving the phosphatidylinositol cyclePharmacokinetics
t½: 24 (18-36)° TMAX: 1-2°Substrate of: Renally cleared
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - Loop diuretics, HCTZ, NSAIDs, & ACEIs can ↑ levels
- - Theophylline, osmotic diuretics, caffeine and steroids result in ↓ levels
Misc
- - more effective in preventing mania than in preventing depression
- - has a suicide protective effect over the long-term course in patients with mood disorders
- - any cause of dehydration can ↑ Li+ levels, including ↑ sweating, vomiting, diarrhea, ↓ fluid intake, low-Na+ diet
Special Populations
Category D—Cardiac malformations, including Ebstein anomaly, are associated with 1st trimester use. AEs include polyhydramnios, cardiac arrhythmias, hypoglycemia, DI, Δ in thyroid function, premature delivery, floppy infant syndrome, Li+ toxicity
Breast-feeding should be be avoided. Li+ is excreted in breast milk (RID 10-50%). Hypotonia, hypothermia, cyanosis, ECG Δ's, & lethargy have been reported in nursing infants
Li+ clearance ↓'s with age & ↓CrCl, thus elderly patients usually require lower Li+ dosages to achieve a target serum concentrations
Li+ clearance ↓'d in patients with abnormal renal function ∴ the risk of Li+ toxicity is ↑'d. Contraindicated severe renal insufficiency. Dosages must be adapted accordingly in mild or moderate reduction in renal function
No dosing adjustment required in liver disease