Lithium

Lithium

Lithium

• Only medication to reduce suicide rate.
  • Rate of completed suicide in BAD ~15%
• Effective in long-term prophylaxis of both mania and depressive episodes in 70+% of BAD I pts
• Factors predicting positive response to lithium
  • Prior long-term response or family member with good response
  • Classic pure mania
  • Mania is followed by depression

Lithium- how to use it

• Before starting :Get baseline creatinine, TSH and CBC. In women check a pregnancy test during the first trimester is associated with Ebstein’s anomaly 1/1000 (20X greater risk than the general population)
• Monitoring: Steady state achieved after 5 days check 12 hours after last dose. Once stable check q 3 months and TSH and creatinine q 6 months.
• Goal: blood level between 0.6-1.2

Indications

• Anti-manic
  • 78% response rate
  • Level I evidence
• Anti-depressant
  • 79% response rate
  • Level I evidence
• Prophylaxis
  • 6 fold decrease in subsequent episodes
  • Level I evidence

Pharmacology

• Half-life = 14-30 hours
• Not metabolized
  • Cleared by kidney (mind renal function)
  • Not protein bound

Side Effects

Lithium side effects

• Most common are GI distress including reduced appetite, nausea/vomiting, diarrhea

• Thyroid abnormalities

• Nonsignificant leukocytosis

• Polyuria/polydypsia secondary to ADH antagonism. In a small number of patients can cause interstitial renal fibrosis.

• Hair loss, acne

• Reduces seizure threshold, cognitive slowing, intention tremor

• Polyuria, polydipsia (Diabetes Insipidus)

  • Treat with diuretics if necessary

• Increase weight

• Cognitive problems

• Tremor

  • Treat with Beta-Blockers

• Sedation

• GI distress

• Increase WBC

• ECG changes

  • Usually benign
  • Rarely conduction abnormality

Other Effects

• Hypothyroid (5-35%)
  • More females after 6-18 month treatment
  • Generally reversible
  • Can replace with thyroxine
• Nephrotoxicity
  • Controversy, but appears to be

Levels and its Side Effects

• 0.4-0.6 mmol/L

  • Decreased side effects
  • Increased risk of episodes

• 0.6-0.8 mmol/L

  • Most often chosen
  • Not well studied

• 0.8-1.1 mmol/L

  • Decreased risk of episodes
  • Increased side effects

• Balance must be chosen between efficacy and side effects

Lithium toxicity

• Mild- levels 1.5-2.0 see vomiting, diarrhea, ataxia, dizziness, slurred speech, nystagmus.
• Moderate-2.0-2.5 nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
• Severe- >2.5 generalized convulsions, oliguria and renal failure

Overdose

• >1.5 mmol/L = Toxic
  • coarse tremor
  • Vomiting
  • Blurred vision
  • Vertigo
  • Confusion
  • Increased DTR
• > 2.5 mmol/L = Life threatening
• Treatment: hemodialysis

What to do before starting:

• Workup – repeat every 6-12 months
  • ECG
  • CBC
  • TSH
  • Creatinine, ‘lytes, u/a
  • Pregnancy test if applicable
• Blood lithium levels
  • 5 days after starting, and then 5-7 days after dosage changes
  • Get 2 therapeutic serum levels, then repeat q3months.

Dosage

• Start at 300 mg PO BID
• Increase by 300 mg/day depending on levels
• Usual dosage 900-1500 mg/day
• Measure “trough” levels
  • Patient to have blood test 12 hours post last dose