What is the recommended dose regimen for lithium therapy?

Lithium Dosage Regimen for Bipolar Disorder

The recommended lithium dosage regimen for bipolar disorder includes starting with 600 mg three times daily for acute mania to achieve serum levels of 1.0-1.5 mEq/L, followed by maintenance therapy with 300 mg three to four times daily to maintain levels of 0.6-1.2 mEq/L, with regular monitoring of serum lithium levels. 1

Initial Dosing

• For acute mania, optimal response is usually established with 600 mg three times daily, targeting serum lithium levels between 1.0-1.5 mEq/L 1
• Initial recommended doses are typically 450-900 mg per day, adjusted based on age and body weight 2
• Lower starting doses (150 mg/day) are recommended for elderly patients due to increased sensitivity to lithium and reduced clearance 3
• Dosage must be individualized according to serum levels and clinical response 1

Maintenance Therapy

• For long-term control, the target serum lithium levels are 0.6-1.2 mEq/L, typically achieved with 300 mg three or four times daily 1
• Standard maintenance daily doses vary by age 2:
  • 925-1300 mg for patients <40 years
  • 740-925 mg for patients 40-60 years
  • 550-740 mg for patients >60 years

Administration Schedule

• Traditional administration is two or three times daily, although once-daily dosing with sustained-release formulations is increasingly recommended 2
• Single daily dosing may improve compliance and potentially reduce long-term renal damage compared to multiple daily dosing 4
• Sustained-release formulations result in 30-50% reductions in peak plasma concentrations and are typically dosed at the upper range of therapeutic levels (0.8-1.0 mmol/L) 2

Monitoring Requirements

• During acute phase treatment, serum lithium levels should be determined twice per week until the serum level and clinical condition stabilize 1
• For maintenance therapy, monitor serum lithium levels at least every two months 1
• Blood samples for serum lithium determination should be drawn 8-12 hours after the previous dose (trough level) 1
• Baseline laboratory assessment should include 5, 3:
  • Complete blood cell count
  • Thyroid function tests
  • Renal function tests (BUN, creatinine, GFR)
  • Serum electrolytes including calcium
  • Urinalysis

Special Populations and Considerations

• For patients with GFR <60 ml/min/1.73 m², consider lower doses and more frequent monitoring 3
• For patients with GFR <30 ml/min/1.73 m², reduce dose by 50% 3
• Elderly patients often require lower doses and may exhibit toxicity at serum levels normally tolerated by others 1
• When lithium is used to augment antidepressants, lower blood levels (0.2-0.6 mEq/L) may be adequate 3
• Weight, creatinine clearance, and total daily dose affect lithium clearance; dosage adjustments are recommended for patients with renal insufficiency 6

Efficacy and Therapeutic Levels

• Research shows that serum lithium levels of 0.8-1.0 mmol/L are more effective in treating bipolar disorder than lower concentrations (0.4-0.6 mmol/L), though higher doses are associated with more side effects 7
• The risk of relapse is 2.6 times higher among patients maintained at lower serum levels (0.4-0.6 mmol/L) compared to standard levels (0.8-1.0 mmol/L) 7

Monitoring for Adverse Effects

• Early signs of toxicity include tremor, nausea, diarrhea, and polyuria-polydipsia 8
• Common side effects at therapeutic levels include tremor, diarrhea, urinary frequency, weight gain, and metallic taste 7
• Serum levels >1.5 mM may have mild and reversible toxic effects on kidney, liver, heart, and glands 9
• Serum levels >2.0 mM may cause neurological symptoms including cerebellar dysfunction 9

Important Precautions

• Avoid concomitant use of NSAIDs as they can increase lithium levels and risk of toxicity 3
• Maintain adequate hydration, especially during intercurrent illness 3
• Renal impairment increases the risk of toxicity 8
• Ongoing monitoring should include renal function tests, thyroid function tests, and urinalysis every 3-6 months 8